Physiology

A wet Amazon may be more resilient to a drying climate than thought: Study – Mongabay.com

In some of the wettest parts of the Amazon rainforest, dry air may increase plant photosynthesis rates a response that contradicts the assumptions of many climate models, according to a recent study published in Science Advances.

When conditions are dry, plants attempt to retain water by closing the tiny pores on their leaves called stomata. But this also reduces the rate of photosynthesis, with knock-on effects for forest growth, carbon absorption, and large-scale weather patterns. Thats the theory, but data on how these dynamics play out at the scale of whole tropical forests is limited.

An international team of researchers led by Julia Green, a postdoctoral researcher at Laboratoire des Sciences du Climat et de lEnvironnement (LSCE) in France, used machine learning to cluster data from nine years of monthly satellite images of South and Central America into areas with similar climate, and modeled the relationship between air moisture and photosynthesis in each cluster. They found that dry tropical forests and savannas showed the expected pattern: photosynthesis slowed in dryer air. However, wetter areas of the Amazon basin displayed a reverse trend, with photosynthesis actually increasing as the air dried, an effect that became even more pronounced in the wet season.

The researchers used sun-induced fluorescence (SIF), a measure of excess light energy released by photosynthesizing leaves, to estimate the rate of photosynthesis using satellite imagery. Experts say there is still scientific debate over the reliability of SIF as a measure of a forests photosynthetic output, known as gross primary production (GPP). Green acknowledged that SIF may be an unreliable measure of GPP at the scale of individual leaves, but said that SIF tracks GPP quite well at the ecosystem scale, and that this relationship has been widely exploited in other studies.

David Lapola, an Earth system modeler at the University of Campinas (UNICAMP) in Brazil, who was not involved in the study, said he is skeptical about the results, but that this article opens up a hypothesis that deserves further investigation.

To photosynthesize, plants face a trade-off. Opening their stomata allows them to absorb CO2, a crucial ingredient for photosynthesis, but in doing so they also lose water through the process of transpiration. At the same time, plants need to maintain a continuous column of water from root to leaf. If there isnt enough water available in the soil to match water loss from the stomata, the water column will become strained and eventually break. To avoid these potentially fatal breaks, plants can partly or fully close their stomata.

The team analyzed four years of hourly data collected at three established monitoring towers in the states of Amazonas, Para, and Tocantins in Brazil, which allowed them to explain the remote sensing findings and try to link the large scale to the small scale, Green said. When the air was dry, plants absorbed less CO2, suggesting that their stomata were fully or partially closed, yet their leaves were releasing the same amount of heat, indicating high rates of photosynthesis.

The authors say this can be explained, at least in part, by leaf ageing. At the beginning of the dry season, trees in wet tropical forests drop the leaves at the top of the canopy, allowing more light through and stimulating growth of plants in the understory. By the time the wet season arrives, the shed leaves have been replaced by young leaves that are able to photosynthesize far more efficiently. Even in the Amazon, the stomata will partially close when the air gets drier, but because of the higher photosynthetic capacity of the young leaves its more than compensated for, Green said.

Marielle Smith, a postdoctoral researcher at Michigan State University in the U.S., who was not involved in the study, says that plentiful soil moisture may explain why plants in wet regions are able to continue photosynthesizing even when the air is very dry.

In a separate study published in Nature Plants in October , Smith and colleagues compared photosynthesis rates with changing air temperature and humidity in a climate-controlled experimental tropical forest biome in Arizona, with data collected at monitoring towers in the Brazilian Amazon, and found declining photosynthesis rates as the air dried, indicating that plants were closing their stomata when they experienced water stress. But if the potential for hydraulic stress is alleviated by sufficient soil water, the response of stomata to air dryness may be reduced or eliminated. This would mean that forests in wet places could take full advantage of the high light availability that tends to accompany dry air, Smith said.

Smith also expressed doubts that dry air was the causal factor behind higher rates of photosynthesis in wet regions. This conclusion is opposite to what we found at the particular sites used in our analyses, she said, despite using data from two of the same monitoring towers.

The source of this disparity, Smith says, is light. If light availability, which tends to be higher when the air is dryer, is controlled for statistically, the rate of photosynthesis at the monitoring towers declines as air dryness increases. The tower analyses they use to validate the artificial neural network analysis of SIF show the opposite: [air dryness] has a negative impact on GPP when GPPs response to light is accounted for, she said. Therefore, some independent validation is required in order for this interesting hypothesis to be convincing.

Experts say controlled experiments are needed to validate and investigate these complex interactions between water availability, climate, and plant physiology in tropical forests. Im leading the effort trying to establish a FACE [free-air carbon dioxide enrichment] experiment near Manaus and it might be that we can also change moisture conditions in the air, Lapola said. This is a very good suggestion that the authors give and is something we will definitely think about.

The researchers applied the same clustering analysis to the outputs from 10 different climate models and found that they failed to replicate the regional differences in photosynthesis found in the satellite data. Models are overestimating water stress in the Amazon rainforest, Green said.

Climate models must accurately represent photosynthetic processes in the Amazon if they are to produce meaningful results, because changes in gas and water exchange between these vast forests and the atmosphere can have widespread impact on climate and weather patterns. This region is bigger than just itself, Green said.

The Amazon rainforest represents a huge stock of carbon and flux of moisture to the atmosphere, Lapola said. This misrepresentation in vegetation models might significantly change the [predicted] carbon cycle and water cycle in the region.

Green says the good news is that this data suggest Amazon forests are potentially more resilient than we thought, but cautioned that if air dryness exceeds levels currently experienced by Amazon forests, the plant physiological responses observed in this study may change.

The team found that the relationship can reverse during extreme weather events, which are also expected to become more frequent and severe as the climate warms. Their analysis included the El Nio event that caused severe and widespread droughts in the Amazon in 2015 and 2016; for that period, we see that this positive response of photosynthesis to air dryness either diminished or reversed, Green said.

Citation:

Green, J. K., Berry, J., Ciais, P., Zhang, Y., & Gentine, P. (2020). Amazon rainforest photosynthesis increases in response to atmospheric dryness. Science advances, 6(47), eabb7232.https://advances.sciencemag.org/lookup/doi/10.1126/sciadv.abb7232

Banner Image: Plants are expected to photosynthesize less in response to dry air, but a machine-learning analysis of satellite data found that the wettest parts of the Amazon basin actually photosynthesize more when the air is dry. Image by CIFOR via Visualhunt (CC BY-NC-ND).

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Immunology

In Survey of Those with Uncontrolled Asthma, Half Smoked Cannabis – Newswise

Newswise ARLINGTON HEIGHTS, IL (Feb. 2, 2021) As the number of states increase where medical and recreational cannabis use is legal, so does the importance that physicians discuss with patients the effects of cannabis on those with asthma. A new survey in Annals of Allergy, Asthma and Immunology, the scientific journal of the American College of Allergy, Asthma and Immunology, shows that of those who used cannabis, about half smoked it while a third vaped both inhalation routes likely to affect ones lungs.

It surprised me that over half of the cannabis users in this study who have asthma were smoking it, said Joanna Zeiger, PhD, principal investigator for the study. And further, of those with uncontrolled asthma, half reported smoking cannabis. We also found that people with asthma are not routinely being asked or advised by their physician about cannabis and how they are consuming it.

Eighty-eight (18%) of the 489 adults with allergy/asthma who completed the survey reported current cannabis use. The majority of those responding were younger than 50 years, female, and White. Among non-cannabis users, 2.5% reported an allergy to cannabis. Two-thirds of current cannabis users did so for medical or medical/recreational purposes. The anonymous survey, conducted in collaboration with Allergy & Asthma Network, was of those 18 years and older and looked at cannabis knowledge, attitudes, and patterns of use.

Strikingly, among current cannabis users, only about 40% report having their physicians inquire about cannabis use, and about the same number of patients want to discuss cannabis with their physicians, says allergist William Silvers, MD, study co-author, ACAAI member and expert on cannabis allergy. In order to more completely manage their allergy/asthma patients, allergists should increase their knowledge about cannabis and inquire about cannabis use including types of cannabinoid, route of use, reasons for use, and adverse effects, says Dr. Silvers. As with cigarette smoking, efforts should be made to reduce smoking of cannabis, and recommend other potentially safer routes such as edibles and sublingual tinctures.

Positive effects of cannabis use (e.g., reduced pain, calm, improved sleep) were reported significantly more frequently than adverse effects (e.g., cough, increased appetite, anxiety). Of concern, about 20% of survey respondents reported coughing from cannabis, which was significantly related to smoking the cannabis. Almost 60% of the cannabis users in the survey reported current asthma, of whom 40% were uncontrolled by the Asthma Control Test.

Says Dr. Zeiger, We look forward to future studies of larger, more diverse cohorts to better explore more deeply the effect of cannabis use on asthma and other allergic disorders.

Allergists are specially trained to diagnose and treat asthma. To find an allergist near you who can help create a personal plan to deal with your asthma and help you live your best life, use the ACAAI allergist locator.

About ACAAI

The ACAAI is a professional medical organization of more than 6,000 allergists-immunologists and allied health professionals, headquartered in Arlington Heights, Ill. The College fosters a culture of collaboration and congeniality in which its members work together and with others toward the common goals of patient care, education, advocacy, and research. ACAAI allergists are board-certified physicians trained to diagnose allergies and asthma, administer immunotherapy, and provide patients with the best treatment outcomes. For more information and to find relief, visit AllergyandAsthmaRelief.org. Join us on Facebook, Pinterest and Twitter.

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In Survey of Those with Uncontrolled Asthma, Half Smoked Cannabis - Newswise

Immunology

New treatment could fight cancer by teaching the body to detect and fight mutated cells – Columbia Missourian

Immunotherapy may be the alternative treatment that revolutionizes cancer treatment working with the body instead of against it.

Treatments such as surgery and chemotherapy may not always permanently remove the cancer, depending on its location, type and stage.

Such treatments are designed to eliminate the mutated cancer cells that have already developed and formed tumors, but they dont always stop the body from continuing to produce more cancer cells.

So what if the body could learn to detect and fight mutated cells that fly under the radar?

A study by MU scientist Diana Gil Pags, PhD, about melanoma tumors in mice has shown that altering immune cells can lead to better results with cancer treatment.

Were trying to add to the arsenal of tools from the immune system that you can use against cancer, Gil Pags said. She emphasized the importance of having multiple treatment options for patients with cancer.

Why is it important to have another way? Because not everyone responds to these types of immunotherapies, Gil Pags said.

In fact, our preliminary research shows that if we combine the immunotherapies that are already in the clinic with our approach, there is an added benefit of mice survival and getting control over the tumor.

Immunology is becoming more foundational for cancer research and treatments. MU research technologist Megan Abergel learned about its expanded applications while working alongside Gil Pags.

I really hadnt realized how much immunology is ingrained in cancer research now, Abergel said.

Its really the hot topic and has been for the last couple years at least. I think its really interesting and promising.

Abergel explained the distinctions in cancer as opposed to other illnesses in terms of the bodys response.

When we get cancer, why is our body not able to mount a response? she said. Because its much more complicated, its using our own cells, so our body doesnt necessarily recognize that its foreign.

Gil Pags has been working on an immunotherapy treatment since 2002. She began by studying exactly how specific immune cells, called T-cells, function. She found a structural part of T-cells that allows the cells to identify diseases.

If it (the T-cell) encounters a healthy cell, there wont be a recognition, and the cell will just go around and do nothing, Gil Pags said. But when there is a positive recognition, the T-cell gets reprogrammed and acquires new capabilities that include being cytotoxic, which means killing cells.

By 2007, the study pointed to the possibility that, if their structure could be manipulated, the T-cells threshold for disease detection could be lowered. This means it would be easier for the body to detect mutated cells or any sort of infection.

These mutations also generate signals that make them easily recognized by the immune system, Gil Pags said. But sometimes those signals are subtle, and they are not enough to turn on the mechanism on the T-cells.

In October 2019, Gil Pags received a grant to develop drugs that work with mice genetics to enhance their T-cells. The goal for the drugs is to bind to the proteins that make up the receptors of the T-cell to lower its detection threshold, Gil Pags said.

That data proved that altering the T-cells made it easier for the mice to get rid of the melanoma tumors and keep them away.

The mice have now become what Gil Pags describes as humanized in order to test other drugs that are meant to bind to human T-cells.

A human protein is added to the mice proteins on the T-cell receptors, so the drugs developed for humans can be tested.

With just one component, weve made human in the mouse T-cells, our human reagent binds to these mouse cells now, Gil Pags said.

One problem with the immunotherapy approach is the level of toxicity that a person may experience during treatment.

Gil Pags explained that by lowering the T-cells inhibitions, the cells may also mistake healthy cells for disease, and the therapy can mimic the symptoms of an autoimmune disorder.

Part of the grant is to evaluate the toxicity inherited in our approach and compare it with other immunotherapies already out in the clinic that target T-cells, she said.

If the drug candidates are not equal to or less than the toxicity levels of existing treatments, the research she conducts wont move forward, she said.

The positive outcome is that, so far, we have learned that at least one of our candidates reproduces the anti-tumor effects of our approach seen in mice, and then it might be good enough to move into the clinic in the near future, she said.

She mentioned the possibility that none of the candidates measure up after considering their anti-tumor effects and side effects. Sometimes negative data is not valued so much, but it is needed to push you into developing better ideas.

Her lab research was disrupted in early 2020 because of COVID-19, but she said it began to pick back up in early fall of 2020.

Researchers will continue to run trials with the mice until they are able to do human clinical trials, she said.

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New treatment could fight cancer by teaching the body to detect and fight mutated cells - Columbia Missourian

Immunology

The COVID vaccines are not rushed and they’re safe – here’s why – WWLTV.com

NEW ORLEANS Most of us know someone who is hesitant to be first in line for the COVID-19 vaccine. In fact, last week we heard the head of Ochsner say some of the medical staff were hesitant as well.

Why? It seems to come down to trust.

We're hearing some ask, How do I know I can trust the vaccine, especially since it came out in about a year, instead of four or five years? It turns out, there's a good answer for that.

Tulane microbiology and immunology expert, Dr. Lisa Morici, says the COVID vaccines were not rushed and there were no corners cut. In fact, the way it tells your immune system to make fighter cells has been studied for 30 years.

It took many years of scientists and engineers making small advances, incremental advances over the years to get the technology to a point where it works terrific. said Dr. Morici.

These are not traditional vaccines. They are called 'plug and play' and are perfectly designed for a pandemic because they can be quickly changed depending on the virus endangering the community.

We already knew these platforms were effective and safe. They've been in tens of thousands, If not hundreds of thousands of people for other diseases.

As for the speed of the clinical trials: For scientists worldwide it was all hands on deck. It was easy to get thousands of volunteers because people wanted to help, and the phases could overlap because pharmaceutical companies did not have the huge financial investment and risk.

The federal government and other agencies committed more than $26 billion towards these vaccines and that's unprecedented,she added.

Data on how well the vaccines worked came out fast, because so many people were infected in the community around those vaccine volunteers.

And so we were able to get the information lightning fast, as opposed to what would typically take us years,said Dr. Morici.

To people who don't want to be first to get vaccinated, you're not.

Tens of millions of doses of these vaccine have been administered to people. They are extremely safe. They are some of the safest vaccines that have ever been developed.

For those worried about long term side effects, Dr. Morici says throughout vaccine history, complications have shown up within two months.

We are well beyond the two month period with these vaccines. Millions, millions of folks, many months have passed. There's no reason to wait,she said.

And the doctor says there are no toxic preservatives in the vaccines. All the ingredients are natural ones that are found in the body.

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The COVID vaccines are not rushed and they're safe - here's why - WWLTV.com

Immunology

AbbVie Reports Full-Year and Fourth-Quarter 2020 Financial Results – BioSpace

NORTH CHICAGO,Ill., Feb. 3, 2021 /PRNewswire/ --AbbVie (NYSE: ABBV) announced financial results for the fourth quarter and full year ended December 31, 2020.

"We successfully completed the transformative Allergan acquisition and delivered another year of strong results in 2020, despite the challenges presented by the global pandemic," said Richard A. Gonzalez, chairman and chief executive officer, AbbVie. "Based on our broad portfolio of diversified growth assets and the robust momentum of our business, we expect impressive growth again in 2021."

Fourth-Quarter Results

Note: "Comparable Operational" comparisons include full-quarter current year and prior year results for Allergan, which was acquired on May 8, 2020, as if the acquisition closed on January 1, 2019, and are presented at constant currency rates and reflect comparative local currency net revenues at the prior year's foreign exchange rates. Refer to the Key Product Revenues schedules for further details. "Operational" comparisons are presented at constant currency rates and reflect comparative local currency net revenues at the prior year's foreign exchange rates.

Recent Events

Full-Year 2021 Outlook

AbbVie is issuing its GAAP diluted EPS guidance for the full-year 2021 of $6.69 to $6.89. AbbVie expects to deliver adjusted diluted EPS for the full-year 2021 of $12.32 to $12.52. The company's 2021 adjusted diluted EPS guidance excludes $5.63 per share of intangible asset amortization expense, non-cash charges for contingent consideration adjustments and other specified items.

About AbbVie

AbbVie's mission is to discover and deliver innovative medicines that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas: immunology, oncology, neuroscience, eye care, virology, women's health and gastroenterology, in addition to products and services across its Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at http://www.abbvie.com. Follow @abbvie on Twitter, Facebookor LinkedIn.

Conference Call

AbbVie will host an investor conference call today at 8:00 a.m. Central time to discuss our fourth-quarter performance. The call will be webcast through AbbVie's Investor Relations website at investors.abbvie.com. An archived edition of the call will be available after 11:00 a.m. Central time.

Non-GAAP Financial Results

Financial results for 2020 and 2019 are presented on both a reported and a non-GAAP basis. Reported results were prepared in accordance with GAAP and include all revenue and expenses recognized during the period. Non-GAAP results adjust for certain non-cash items and for factors that are unusual or unpredictable, and exclude those costs, expenses, and other specified items presented in the reconciliation tables later in this release. AbbVie's management believes non-GAAP financial measures provide useful information to investors regarding AbbVie's results of operations and assist management, analysts, and investors in evaluating the performance of the business. Non-GAAP financial measures should be considered in addition to, and not as a substitute for, measures of financial performance prepared in accordance with GAAP. The company's 2021 financial guidance is also being provided on both a reported and a non-GAAP basis.

Forward-Looking Statements

Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, the failure to realize the expected benefits of AbbVie's acquisition of Allergan or to promptly and effectively integrate Allergan's business, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2019 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its Quarterly Reports on Form 10-Q and in other documents that AbbVie subsequently files with the Securities and Exchange Commission that update, supplement or supersede such information. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

AbbVie Inc.

Key Product Revenues

Quarter Ended December31, 2020

(Unaudited)

% Change vs. 4Q19

Net Revenues (in millions)

Reported

Comparable Operational a, b

U.S.

Int'l.

Total

U.S.

Int'l.

Total

U.S.

Int'l.

Total

NET REVENUES

$10,665

$3,193

$13,858

65.9%

40.4%

59.2%

9.4%

(1.2)%

6.8%

Immunology

4,988

970

5,958

18.9

(0.1)

15.3

18.9

(2.5)

14.8

Humira

4,293

859

5,152

8.2

(9.4)

4.8

8.2

(11.4)

4.4

Skyrizi

451

74

525

>100.0

>100.0

>100.0

>100.0

>100.0

>100.0

Rinvoq

244

37

281

>100.0

>100.0

>100.0

>100.0

>100.0

>100.0

Hematologic Oncology

1,373

416

1,789

11.7

30.9

15.7

11.7

29.9

15.5

Imbruvicac

1,165

259

1,424

8.6

15.7

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AbbVie Reports Full-Year and Fourth-Quarter 2020 Financial Results - BioSpace

Immunology

Gossamer Bio to Host Webcast Focused on its Inflammatory Bowel Disease Program, GB004, on February 18, 2021 – Business Wire

SAN DIEGO--(BUSINESS WIRE)--Gossamer Bio, Inc. (Nasdaq: GOSS), a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology, today announced that it will host a conference call and webcast for investors and analysts on Thursday, February 18, 2021 at 11:00am ET to discuss GB004, its oral HIF-1 stabilizer for the treatment of inflammatory bowel disease (IBD), including ulcerative colitis (UC).

Gossamer management will present alongside key IBD and HIF biology opinion leaders, including:

As part of the event, Gossamer Bio management and Drs. Sandborn, Danese, and Taylor will be available for questions.

William Sandborn, M.D., is a board-certified gastroenterologist, who is one of the world's top experts in the management of ulcerative colitis and Crohns disease. He directs the Inflammatory Bowel Disease Center at UC San Diego Health. In addition, he is Chief of the Division of Gastroenterology for UC San Diego Health. A Professor in the Department of Medicine at UC San Diego School of Medicine, Dr. Sandborn conducts clinical trials in IBD and leads a team of physicians, research fellows, nurses, and study coordinators. His clinical trials have been instrumental to developing modern treatments for IBD. Dr. Sandborn has published 836 articles in prestigious journals, including the New England Journal of Medicine, The Lancet, JAMA, the Annals of Internal Medicine, and Gastroenterology. Prior to joining UC San Diego Health, Dr. Sandborn worked in the Division of Gastroenterology and Hepatology at the Mayo Clinic in Rochester, Minnesota. Dr. Sandborn completed his fellowship at Mayo Clinic. He did his residency and earned his medical degree at Loma Linda University School of Medicine.

Silvio Danese, M.D., Ph.D., is the Head of the Inflammatory Bowel Disease Center at Humanitas Research Hospital and the group leader of the Gastrointestinal Immunopathology Laboratory at Humanitas Research Center in Milan, Italy. A Professor of Gastroenterology at Humanitas University, his main research area of interest is the investigation of the fundamental mechanisms underlying IBD pathogenesis. He served as President of the European Crohns and Colitis Organization (ECCO) in 2019 and has served as the Principal Investigator on many Phase 1, 2 and 3 clinical trials for the treatment of IBD patients. He is also Member of the Editorial Board of Current Drug Target and Alimentary Pharmacology & Therapeutics and Associate Editor of Gut and Journal of Crohns and Colitis. He has published more than 300 research articles in peer-reviewed journals with high impact factor. He trained in gastroenterology at Policlinico Gemelli, Rome, Italy, and earned his Ph.D. there in 2004. Professor Danese also worked in Professor Claudio Fiocchis laboratory at the Case Western Reserve University, Cleveland, Ohio from 2001 to 2004.

Cormac Taylor, Ph.D., is a Professor of Cellular Physiology at the School of Medicine and Medical Science and the Conway Institute, University College Dublin, Ireland. He leads the Taylor Lab, in which research is directed towards expanding the understanding of the physiological and pathophysiological mechanisms by which changes in micro-environmental oxygen levels regulate gene transcription in cells. A key focus of this work is the identification of new therapeutic targets in inflammatory bowel disease. Dr. Taylor was elected as a Member of the Royal Irish Academy in 2014. He was awarded the 2014 Nature mid-career mentorship award and the 2017 Takeda Distinguished Researcher Award from the American Physiological Society. He has authored over 130 articles in journals including Gastroenterology, Gut, PNAS and Science and is an Editorial Board Member of the American Journal of Physiology and the Journal of Biological Chemistry. Dr. Taylor received his Ph.D. in Pharmacology from UCD in 1996 prior to a postdoctoral fellowship at Harvard Medical school from 1996-2001 and has been running his own independent research group since 2001.

Conference Call and Webcast

Gossamer will host a conference call and live audio webcast at 11:00 am ET on Thursday, February 18. The live audio webcast may be accessed through the Events / Presentations page in the Investors section of the Company's website at http://www.gossamerbio.com. Alternatively, the conference call may be accessed through the following:

Conference ID: 6135079Domestic Dial-in Number: (833) 640-7726International Dial-in Number: (602) 585-9912Live Webcast: https://edge.media-server.com/mmc/p/9tbs35gb

A replay of the audio webcast will be available for 30 days on the Investors section of the Company's website, http://www.gossamerbio.com.

About Gossamer Bio

Gossamer Bio is a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology. Its goal is to be an industry leader in each of these therapeutic areas and to enhance and extend the lives of patients suffering from such diseases.

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Gossamer Bio to Host Webcast Focused on its Inflammatory Bowel Disease Program, GB004, on February 18, 2021 - Business Wire

Immunology

Jnana Therapeutics Expands Leadership Team with Two Experienced Biopharmaceutical Executives – Yahoo Finance

Company appoints Nick Pullen, PhD, as Senior VP, Head of Biology and Brian Danieli as VP, Head of Finance & Operations

Jnana Therapeutics, a biotechnology company targeting the solute carrier (SLC) family of metabolite transporters to treat underserved diseases, today announced that it has expanded its leadership team with the appointment of two accomplished biopharmaceutical executives: Nick Pullen, PhD, as Senior Vice President, Head of Biology, and Brian Danieli as Vice President, Head of Finance and Operations. These new executives join Jnana at a significant time in the companys evolution as it advances its first SLC transporter-targeted therapies toward clinical development.

Nick Pullen, PhD, Senior Vice President, Head of Biology

"Nick is an experienced and passionate leader in drug discovery and development with deep knowledge in several therapeutic areas, including renal disease and inflammation, that are highly relevant to our R&D work with SLC transporters," said Joel Barrish, PhD, co-founder and Chief Scientific Officer of Jnana Therapeutics. "We are delighted to welcome Nick to our team and look forward to his contributions in building our research and development strategy and helping guide our lead programs toward the clinic."

In the role of Senior Vice President, Head of Biology, Dr. Nick Pullen will work to further leverage Jnanas RAPID platform to systematically target SLC transporters and develop novel small molecule drug candidates. Dr. Pullen is an experienced drug discovery and development leader with 20 years of experience and a proven track-record of therapeutic innovation across multiple disease areas. Before joining Jnana, he was Vice President, Integrative Sciences, Inflammation & Immunology, Cardiovascular & Fibrosis, at Bristol Myers Squibb and prior to this, he served as Executive Director, Inflammation & Immunology for Celgene. In both of these roles, Dr. Pullen was responsible for scientific and strategic leadership of externalized drug discovery programs applying novel technologies and scientific insights to the expansion of the Inflammation & Immunology portfolio as well as more broadly. Dr. Pullen brings extensive experience in Inflammation & Fibrosis, following a career at Pfizer which spanned more than 15 years and brought multiple development candidates to clinical evaluation and touched many disease areas including renal disease, IBD and NASH, a breadth of experience with significant pertinence to the emerging Jnana portfolio. Dr. Pullen received his PhD in biochemistry from the University of Southampton in the UK.

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"The Jnana team have made remarkable progress in the development of technologies that open up the therapeutic opportunity afforded by targeting the SLC gene family. I am thrilled to be joining Jnana at this exciting stage in the companys growth and to help them build a pipeline of small molecules targeting SLC transporters," said Dr. Pullen.

Brian Danieli, Vice President, Head of Finance & Operations

"Brians extensive finance background and expertise will be a critical addition to the organization," said Caroline Stark Beer, Jnanas Chief Business Officer. "Were very pleased to welcome Brian to Jnana and look forward to Brians financial and operational leadership as we enter a new stage of growth."

As the Head of Finance and Operations of Jnana Therapeutics, Brian Danieli will expand the companys finance and operations infrastructure to allow for growth to a clinical-stage drug developer. Mr. Danieli is an expert finance leader with more than 20 years of global experience with fast-growing biotechnology companies. He joins Jnana from Momenta Pharmaceuticals, where he led Financial Planning & Analysis. Previously, he served for more than 20 years in roles of increasing responsibility at Sanofi Genzyme. His most recent position at Sanofi Genzyme was Head of Finance for North America Rare Disease and Rare Blood Disorders, and he drove all aspects of strategic financial planning and operations for the North American region for two business units representing $2B in combined sales with over 500 employees and 12 products. In his roles at Sanofi Genzyme, Mr. Danieli spearheaded the integration of Bioverativ and Ablynx acquisitions, implemented financial modeling and assembled franchise performance metrics for investor audiences. Earlier in his career, he held financial positions at Blue Cross Blue Shield of Massachusetts and KPMG. He earned a BS in accounting from Boston College.

"I am eager to leverage my experience to support Jnanas evolution in the next stage of its business," said Mr. Danieli. "I see tremendous potential for Jnanas platform to bring innovation to a range of diseases, and I am excited to be part of a team that is committed to bring novel medicines to make a difference in the lives of patients."

About Jnana Therapeutics

Jnana Therapeutics is a biotechnology company focused on opening the solute carrier (SLC) family of metabolite transporters as a target class to develop transformational therapeutics. Jnana uses its RAPID platform, a proprietary, cell-based drug discovery approach, to systematically target SLC transporters and develop best-in-class therapies to treat a wide range of diseases, including immune-mediated, neurological and metabolite-dependent diseases. Headquartered in Boston, Jnana is founded by world-renowned scientists and backed by leading life science investors. For more information, please visit http://www.jnanatx.com and follow us on Twitter and on LinkedIn.

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Contacts

Kathryn MorrisThe Yates Networkkathryn@theyatesnetwork.com 914-204-6412

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Immunology

Spherix Global Insights Introduces New Service Focusing on Recent Launches in Expanding Immunology, Nephrology, and Neurology Markets – Daily Local…

EXTON, Pa., Jan. 29, 2021 /PRNewswire/ --Spherix Global Insights, a leading market intelligence firm specializing in select dermatology, gastroenterology, nephrology, neurology, and rheumatology markets, announces the inaugural publications of their newest service offering, Launch Dynamix. This innovative, independent service provides monthly benchmarking of newly launched products for the first eighteen months of commercial availability.

This is augmented by a quarterly deep dive into promotional activity, messaging, drivers of use, barriers to uptake, patient types, market access landscape, and degree of disruption surrounding the newly launched product including a mix of both quantitative and qualitative feedback. Clients subscribed to this service received their first monthly pulse on January 15, 2021, including data benchmarking the current launch to relevant historical market entrants at similar post-entry timings.

In rheumatology, Spherix is currently tracking the entry of both Novartis' Cosentyx and Eli Lilly's Taltz in non-radiographic axial spondylarthritis (nr-axSpA), which were approved within weeks of each other in June of last year. Data on the key performance indicators (KPIs), provided in the January publication, are compared to the performance of UCB's Cimzia, which was the first biologic/advanced systemic agent to gain FDA approval for nr-axSpA in March of 2019.

With regard to psoriatic arthritis (PsA), Spherix's new service is available for Janssen's Tremfya, with KPIs benchmarked to Cosentyx, Taltz, Amgen's Otezla, and Pfizer's Xeljanz. Pending FDA approval, Spherix also plans to cover AbbVie's Rinvoq in both ankylosing spondylitis (AS) and PsA, Xeljanz for the treatment of AS, and AstraZeneca's anifrolumab for the treatment of systemic lupus erythematosus.

Inaugural Launch Dynamix coverage in gastroenterology includes tracking and trending of Janssen's Stelara for the treatment of ulcerative colitis (UC), benchmarking the entry of the IL-12/23 inhibitor to the respective Crohn's disease launch, as well as the launch of Xeljanz for the treatment of UC.

In neurology, Spherix is currently covering the launches of Novartis' Kesimpta and BMS' Zeposia, with appropriate benchmarked KPIs to Genentech's Ocrevus, Novartis' Mayzent, EMD Serono's Mavenclad, and Biogen's Vumerity. Pending approval, Spherix will also cover the launch of Janssen's ponesimod, which is expected to be available in the Spring of 2021.

In an area of significant unmet need, the lupus nephritis market is poised for a massive shift with recent drug approvals for GSK's Benlysta (also approved for systemic lupus erythematosus) and Aurinia Pharmaceuticals' Lupkynis. The study will include responses from both nephrologists and rheumatologists, with the first pulse available in February.

Other launches on Spherix's radar with planned 2021 coverage (pending approval) include:

"We are really excited to be able to bring this level of launch detail to our clients," says Lynn Price, Vice President of Strategy and Innovation at Spherix. "The rapid turn-around from fielding to publication and the monthly cadence coupled with quarterly deep-dives provides those with assets in this market or with near-term plans to enter it the perfect tool to keep their finger on the pulse."

About Launch Dynamix

Launch Dynamix is an independent service providing monthly benchmarking of newly launched products for the first eighteen months of commercial availability, augmented by a quarterly deep dive into patient types initiated, brand perceptions, promotional activity, and drivers and barriers to uptake. The service is offered on a brand-by-brand basis.

Learn more about our services here.

About Spherix Global Insights

Spherix Global Insights is a hyper-focused market intelligence firm that leverages our own independent data and expertise to provide strategic guidance, so biopharma stakeholders make decisions with confidence. We specialize in select dermatology, gastroenterology, nephrology, neurology, and rheumatology markets.

All company, brand or product names in this document are trademarks of their respective holders.

For more information contact:

Kristen Henn, Business Development Manager

Email:info@spherixglobalinsights.com

http://www.spherixglobalinsights.com

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Immunology

IncellDx Files Patent for COVID Long Hauler Index and Active COVID-19 Severity Score – BioSpace

Company launches http://www.covidlonghaulers.com website to facilitate immune profiling and therapy

SAN CARLOS, Calif., Feb. 3, 2021 /PRNewswire/ -- IncellDx, a leading precision medicine diagnostics company, has filed patents for algorithms identifying immunologic profiles unique to COVID long haulers and patients with severe COVID.

IncellDx has developed and patented two distinct algorithms using machine learning, built on a tailored panel of cytokines and chemokines specific for abnormalities in cytokine storm conditions and in chronic COVID patients (often referred to as COVID "long haulers"). These have been submitted for publication (pre-print available through BioRx https://www.biorxiv.org/content/10.1101/2020.12.16.423122v1).

The first algorithm generates a severity score based on analysis of hundreds of COVID-19 patients spanning the spectrum of disease severity from mild to critical. The second algorithm derived from the same cytokine/chemokine immune panel, demonstrates that the immunology of long haulers is distinct from active COVID-19. This objective algorithm offers the opportunity for precision medicine to be used by physicians as a guide in the care of COVID-19 patients.

Bruce Patterson, M.D., CEO of IncellDx, commented that "Since the beginning of the COVID-19 pandemic, IncellDx has led the way in using biomarkers to develop precision medicine approaches to therapy including the post-COVID-19 long haulers. A recent preprint of a meta-analysis suggests as many as 80% of individuals infected by COVID-19 may have at least one symptom long after infection."

IncellDx, in collaboration with Drs. Ram Yogendra and Purvi Parikh, launched the website http://www.covidlonghaulers.com on January 29, 2021. The site will serve as a resource for patients and clinicians who are dealing with the long-term complications of COVID-19. The new COVID long hauler index and severity score will likely play an important role in providing clinicians with immunological information that will aid them in caring for these patients.

Ram Yogendra, M.D. of the ECA Wellness Center, said that "through our research on chronic COVID, we recognize that there is a significant group of patients who have debilitating symptoms and complications weeks and months after the initial infection. We believe our long hauler index and treatment center are key steps in addressing this growing public health crisis."

Purvi Parikh, M.D., Immunologist, Allergist and COVID -19 researcher, stated that "as with everything in this pandemic, many of the devastating and long-term side effects of this virus are mysterious and uncertain. So much attention is paid to the death rate, but we are missing those whose quality of life has been completely changed by this terrible virus. I am happy we are at the start of a journey to help find answers for these COVID patients who continue to struggle months later. "

About IncellDx

IncellDx, Inc., located in San Carlos, California, is a single-cell, molecular diagnostics company dedicated to revolutionizing healthcare, one cell at a time. By combining molecular diagnostics with high throughput cellular analysis, the company's focus is on critical life threatening diseases in the areas of COVID-19, infectious disease and oncology/immuno-oncology, i.e., cervical, head and neck, lung, bladder, breast and prostate cancers.

CONTACT: Chris Meda, 650-777-7630

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Immunology

[Full text] Lipid Profile and IL-17A in Allergic Rhinitis: Correlation With Diseas | JAA – Dove Medical Press

Dina Sheha,1 Lobna El-Korashi,2 Amany M AbdAllah,3 Marwa M El Begermy,4 Doaa M Elzoghby,5 Amira Elmahdi1

1Department of Internal Medicine, Allergy and Clinical Immunology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 2Department of Medical Microbiology and Immunology, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 3Department of Family Medicine, Faculty of Medicine, Zagazig University, Zagazig, Egypt; 4Department of Otorhinolaryngology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; 5Department of Clinical Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Correspondence: Dina ShehaFaculty of Medicine, Ain Shams University, El-Abbassia Street, Cairo, 11566, EgyptTel +20 1001525144Email DinaSheha@med.asu.edu.eg

Background: Recent data display the possible role of cytokines such as interleukin-10 (IL-10), IL-17 and IL-23 as a link between dyslipidemia and atopy; however, the relationship between dyslipidemia, allergic rhinitis (AR), and the underlying mechanisms involved is unclear.Purpose: To measure the lipid profile and IL-17A level in AR patients in comparison to healthy controls, and correlate serum lipid level with the severity of symptoms and quality of life (QoL) of AR patients.Patients and Methods: Peripheral blood samples were collected from AR patients (n=70) and a control group (n=80). Samples were analyzed for serum total IgE by ELISA, serum lipid profile, and IL-17A level by ELISA. Severity of AR symptoms was assessed by visual analogue scale (VAS) score and the rhinoconjunctivitis QoL questionnaire.Results: Serum lipid profile and level of IL-17A in AR patients were significantly higher in comparison to controls (P < 0.001). Positive correlations were found between total cholesterol (TC) and the severity of AR and QoL. IL-17A was positively correlated with triglyceride (TG) level and low-density lipoprotein cholesterol (LDL-C) (P=0.011, r=0.303; P=0.043, r=0.242, respectively). Additionally, IL-17A was negatively correlated with high-density lipoprotein cholesterol (HDL-C) level (P=0.036, r= 0.251). IL-17A was positively correlated with both age and VAS score with statistical significance (P=0.033, r=0.225; P=0.011, r=0.302, respectively).Conclusion: Dyslipidemia might play a potential role in the severity of AR symptoms and impairment of patients QoL. Highlighting this association might alert physicians to evaluate the lipid profile in AR patients for timely diagnosis and treatment of dyslipidemia in an attempt to improve disease control and improve QoL.

Keywords: allergic rhinitis, cholesterol, dyslipidemia, IgE, interleukin-17, quality of life

Allergic rhinitis (AR) is a symptomatic disorder induced by exposure of the nasal mucosa to diverse aeroallergens that is mediated through immunoglobulin E (IgE) hypersensitivity reactions. AR is characterized by four cardinal symptoms of watery rhinorrhea, nasal obstruction, nasal itching and sneezing.1 AR has a wide prevalence, it is estimated to affect 2030% of adults and up to 40% of pediatrics.2 AR is associated with multiple comorbid disorders, including asthma, conjunctivitis, eczema, rhinosinusitis, adenoid hypertrophy, obstructive sleep apnea, disordered sleep with consequent educational and behavioural effects. These associated comorbidities negatively correlate with the quality of life (QoL), and work performance.3

Dyslipidemia is a major risk for atherosclerosis and cardiovascular diseases especially coronary heart disease (CHD), and may play a major role earlier than other risk factors.4 Dyslipidemia modulates the immune response through the release of pro-inflammatory mediators, activation of immune cells (eg, B-cell, T-cells and dendritic cells),5 promoting polarization of T-helper 2 (Th-2) and Th17 and downregulating interleukin-10 (IL-10) cytokine synthesis.6 Th2 and Th17 release cytokines as IL6, IL-1, IL-4, and IL-17.7 Th2 immune response with an increased production of IL-4 and tumour necrosis factor- (TNF-) has been described in AR.8

IL-17 cytokine, produced by Th17 cells, plays a pivotal role in host defense reactions, inflammatory diseases and allergic responses.IL-17 belongs to a family of cytokines that includes six members of different homology and function: IL-l7 (also IL-17A) IL-17B, IL-17C, IL-17D and IL-17 E.9 The role of TNF- and IL-17 in the pathogenesis and regulation of inflammation in autoimmune diseases such as psoriasis has been described previously.10,11 Serum IL-17A level correlated significantly with clinical and inflammatory markers in patients with persistent moderate to severe AR evaluated during the pollen season. Moreover, studies suggest that serum IL-17A level correlates with symptom scores and with the number of peripheral blood eosinophils, suggesting that Th-17 cells may be involved in the chronic allergic reaction. Authors even proposed IL-17A as a new biomarker of disease progression and allergy.12 Research suggests a link between cholesterol and the adaptive immune system, as both have the same immunological pathways involving Th1 toTh2 switch, an increase in Th2 related IgG1 and IgE release, and elevation of pro-inflammatory Th2 cytokines release such as IL-4.13

Numerous research investigated the association between dyslipidemia and allergic diseases. Fessler et al14 demonstrated the relationship between total cholesterol (TC) level and atopy in children 617 years of age. Ouyang et al15 reported increased allergic sensitisation with elevated low-density lipoprotein cholesterol (LDL-C) level. Kusunoki et al16 demonstrated a positive association between TC and LDL-C levels and the allergic sensitization in school-aged children. Similarly, a meta-analysis of ten studies investigated the lipid profile of asthmatics and found higher levels of LDL and low level of high-density lipoprotein (HDL) in asthma patients in comparison to controls.17 Vinding et al18 found higher LDL and triglycerides (TG) were associated with asthma, airway obstruction and higher incidence of aeroallergen sensitization. Elevated HDL was associated with reduction of airway obstruction and lower risk of aeroallergen sensitization. To our knowledge, only a few studies have explored the association of abnormal serum lipids in AR patients and its effect on disease severity.

Since IL-17A could represent a link between AR and dyslipidemia, we aimed to investigate the possible relationship between AR, IL-17A level and dyslipidemia, and correlate level with the severity of AR and QoL of AR patients.

Seventy adult AR patients and 80 healthy volunteers as a control group were enrolled in the current casecontrol study, conducted from March 2019 to August 2019. AR patients were selected by systematic randomization from patients attending the allergy outpatient clinic at Ain Shams University, Cairo and Zagazig University, Zagazig, Egypt. Laboratory Techniques were performed in the Medical Microbiology and Immunology Department, Zagazig University, Zagazig, Egypt. Healthy controls were apparently healthy individuals who were recruited from relatives of patients attending the internal medicine outpatient clinic. They had no chronic diseases or allergic disorders, they were not on regular medications and had no complaints concerning mental or physical health.

AR was diagnosed according to the Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines.19 Inclusion criteria were atopic adult AR with a positive family history of atopy and positive skin prick test (SPT) for at least one inhalant allergen. Patients with asthma, those on statin therapy, patients with acute illness like high-grade fever, first 2 weeks following surgery, non-allergic inflammatory nasal pathology, sleep disorders, diabetics, obese patients, hypothyroid, hypertensive patients, smokers and patients with autoimmune disorders were excluded from the study. No patients received systemic steroids or immunotherapy within 1 month of enrollment. An informed verbal consent was obtained from all participants. The research ethics committee of Zagazig University approved the study (IRB number 6222-25-6-2020) and the procedure outlined for the obtainment of verbal consent. The whole process was documented and the consent was conducted with an impartial witness after which the consent was transcribed. The study procedure complies with the country regulations about subjects data protection and maintaining their integrity, and the study was conducted in accordance with the declarations of Helsinki.

Detailed medical history of allergy was collected from each participant including family history of atopy. Clinical examination (ear, nose, throat and chest examination), and SPT to common aeroallergens were performed in the clinic. Venous blood samples for serum lipid profile, serum total IgE and serum level of IL-17A weredrawn from all participants.

The severity of AR was measured using the visual analogue scale (VAS) score for global assessment of severity of nasal and non-nasal symptoms. AR patients were asked to rate the combination of the nasal and non-nasal symptoms on a scale (010 cm) as follows:

Mild: 03; Moderate: 3.17; Severe: 7.110.19

QoL was assessed in the AR group by the RQLQ total score. The instrument has 28 items in seven domains (sleep, non-rhinoconjunctivitis symptoms, practical problems, nasal symptoms, eye symptoms, activity limitations, and emotional function). The overall RQLQ score is the mean of all 28 responses.19

Skin testing was performed on AR patients according to Bernstein et al.20 A panel for the most common locally encountered inhaled allergens was used including house dust mites, cockroach, cotton, molds mix, ragweed, mugwort, Chenopodium album, hay dust, pigeon feathers, dog hair, cat hair, rabbit hair. Allergen extracts of skin testing were locally prepared at Allergy and Immunology Unit, Department of Internal Medicine, Faculty of Medicine, Ain Shams University. Aqueous allergen extracts (1:100 wt/vol) preparation was done according to allergen extract preparation guidelines developed by the AAAAI/ACAAI/JCAAI and all aqueous allergen extracts were stored at 4 C.21

The maximum or mean diameter of the wheal to various allergens was read at 15 minutes. A wheal of 3mm or more in diameter was considered positive (indicating sensitization to the allergen).

Under complete aseptic conditions, 10mL of fasting venous blood was obtained by a clean venipuncture in the early morning from all participants after 912 hours of fasting. Patients were on regular average diet 3 days before sampling. The serum was separated by centrifugation (1000 g for 15 minutes) and divided into three tubes. Serum of one tube was immediately assayed for lipid profile (TC, TG, HDL-C and LDL-C), while the serum collected in the other tube was stored at 20C for subsequent assay of the serum total IgE, IL-17A concentrations. Hemolysed samples were discarded. Repeated freezing and thawing was avoided.

Serum TC, triglycerides and HDL-C were assayed on Microlab 300 Semi Automated Clinical Chemistry Analyzer supplied by EliTech clinical system (France,www.elitechgroup.cominfo@elitechgroup.com).

TC, TG and HDL-C were assayed by (homogenous for HDL-C) enzymatic colorimetric quantitative determination at wavelength (500, 500, and 600/700 nm respectively) using kits provided by Human diagnostics kit (Human Gesellschaft fr Biomedica und Diagnostica mbH Max-Planck-Ring 21.6 5205 Wiesbaden-Germany). LDL-C was calculated according to the Friedwald equation.22

Dyslipidemia was defined according to the American College of Cardiology/American Heart Association (ACC/AHA) Blood Cholesterol 2013 Guideline, as follows: hypercholesterolemia was defined as total cholesterol (TC) level greater than 200 mg/dL and/or LDL-C level greater than 100 mg/dL, hypertriglyceridemia as TG level greater than 150 mg/dL; and low HDL-C lower than 40 mg/dL in men and 50 mg/dL in women.23

Quantitative measurement of total IgE in the serum was done using a commercially available quantitative enzyme-linked Immunosorbent assay (ELISA) Kit supplied by Calbiotech Inc. (1935 Cordell Ct., El Cajon, CA 92020, USA) according to the manufacturers instructions, and the results were expressed in IU/mL.

Human IL17-A was measured by commercially available quantitative ELISA Kit supplied by Thermo Fisher Scientific (Bender Med Systems gmbH/Campus Vienna Biocenter 2/1030 Vienna, Austria) according to the manufacturers instructions and expressed in pg/mL.

Data analysis was performed using the software SPSS (Statistical Package for the Social Sciences) version 20 (SPSS Inc., Chicago, Illinois, USA). Quantitative variables were described using means and standard deviations. Categorical variables were described using absolute frequencies and to compare the proportion of categorical data, chi square test was used when appropriate. KolmogorovSmirnov (distribution-type) and Levene (homogeneity of variances) tests were used to verify assumptions for use in parametric tests. To compare the means of two groups, independent sample t-test was used. MannWhitney test was used to compare continuous variables between two groups when data were not normally distributed. Pearson correlation and Spearman rank correlation coefficients were used to assess the strength and direction of a linear relationship between two variables. The level of statistical significance was set at 5% (P<0.05). Highly significant difference was present if P0.001.

Descriptive data of the study groups are represented in Table 1. Patients and controls were matched regarding age and gender. The mean age of AR patients was 30.74 years ( 7.24) and controls were 32.85 years ( 7.5). Total IgE and IL17-A level were significantly higher in cases in comparison to controls (Table 1). Runny nose, sneezing, nasal obstruction, postnasal drip, itchy nose, cough and eye symptoms prevailed in 60%, 62.9%, 72.9%, 30%, 20%, 38.6% and 10% of the patients within AR group, respectively.

Table 1 Demographic and Laboratory Data Characteristics of the Study Groups

Associated allergic conjunctivitis and atopic dermatitis co-existed in 30% and 3% respectively of those patients (Table 1)

Levels of TC and LDL-C were statistically significantly higher in cases than controls. Mean SD of TC in cases and controls was 225,6562.91mg/dl and 187.9235.24mg/dl, respectively.

Regarding HDL_C, meanSD in cases was 47.255.36 mg/dl and in controls 49.834.29 mg/dl, showing statistically significantly lower levels in cases than controls. There was a non-significant difference in serum TG and very-low-density lipoprotein cholesterol (VLDL-C) between the two groups (P=0.79, P=0.175) (Table 2).

Table 2 Serum Lipid Profile of Study Subjects

AR patients had significantly increased risk of dyslipidemia by 6.27-fold (95% confidence interval (CI) of crude odds ratio (COR)=2.7114.51, P<0.001). Approximately 44% of the patients with AR had dyslipidemia versus 11.2% of the healthy controls.

Correlation studies were performed to assess the relationship between serum lipid profile and the severity of AR assessed by VAS (P=0.039, r=0.31) and RQLQ score (P=0.04, r=0.247). There was a positive correlation between IL-17A and TG and LDL-C levels (P=0.011, 0.043, respectively). IL-17A level was negatively correlated to HDL-C level (P=0.036), while no significant correlation was found for the other correlation studies listed in Table 3.

Table 3 Correlation Between Serum Lipid Profile and Different Study Parameters

There was a statistically significant correlation between IL-17A and both age and VAS score (p=0.033, r=0.225, 0=0.011, r=0.302; 95% CI; 0.078:0.486) and VAS score (95% CI; 0.078:0.486). On the other hand, there was a non-significant correlation between IL-17A and total IgE and RQLQ score (Table 4).

Table 4 Correlation Between IL-17A and All of Patients Age, VAS, RQLQ, and Total IgE

Serum lipid levels and their clinical implication in the management and monitoring of cardiovascular diseases or diabetic patients is well established.24,25 On the contrary, the role of dyslipidemia in AR is not fully elucidated.

The current casecontrol study aimed to investigate the possible relationship between AR, IL-17A level and dyslipidemia and correlate levels with the severity of AR and QoL of AR patients. We included 70 AR patients and 80 healthy controls, and found dyslipidemia in 44% of AR patients versus 11.2% of controls. Levels of TC and LDL-C were significantly higher in AR patients, while HDL-C was significantly lower. Similarly, recent studies have demonstrated a significant association between high serum lipid levels and AR.26,27 Additionally, Schfer et al investigated the effect of serum cholesterol on atopy and found that elevation of serum cholesterol is associated with an increased incidence of atopic diseases.28 Recent publications suggest the role of dyslipidemia in promoting atopic inflammation, through polarizing Th2 response.7,29 Another proposed theory is the cholesterol trafficking. Cholesterol is a critical microdomain of cell wall lipid rafts that plays an essential role in cell signaling. Changes in these cholesterol rafts trigger the toll-like receptor-signaling pathway of the innate immune reaction, which in turn aggravates the atopic inflammation.30

We report a positive correlation between TC levels and both VAS score, and RQLQ score. Ahmed et al in a recent Egyptian study reported similar results,29 which was also confirmed by regression analysis of Yon et al.31 TC and LDL-C were associated with the severity of AR high TC, which has been reported to increase allergen-specific IgE synthesis thus exacerbating allergic symptoms, which denotes a positive correlation between dyslipidemia and atopy.32 This could be attributed to the impact of dyslipidemia on the immune system where dyslipidemia induces a shift toward an immunologic Th2-oriented response and exacerbates allergic inflammation.26,33 Additionally, hypercholesterolemia is known for being pro-inflammatory, inducing the release of inflammatory cytokines30 and in turn aggravating the symptoms of AR.

We assume the poor QoL is due to the burden of increased AR severity, as well as the socioeconomic and financial burden of treatment costs, and the metabolic burden of dyslipidemia. The inflammatory nature of AR causes nasal obstruction, sleep difficulties, snoring, hypersomnolence, diminished work performance, and finally insomnia that all negatively impact the patients QoL.

Several studies have suggested that metabolic factors, such as dyslipidemia, are related to allergic diseases, but the related causal mechanisms remain elusive.3436 Hence we investigated the role of IL-17A as a link between AR and dyslipidemia, in order to explore one of the cytokines incriminated in the pathogenesis.

We found higher levels of IL-17A in AR patients compared to controls. Similarly, many studies declared this finding.3743 Moreover, other studies found higher IL-17A positive cells in peripheral blood and nasal mucosa of AR patients compared to healthy controls.44,45 It seems that Th17 cells may be involved in the process of neutrophil infiltration that occurs during the acute phase of allergic reaction.46 Besides, IL-17 induces allergen-specific Th2 cell activation, hence the production of serum IgE and eosinophil accumulation suggesting a regulatory role in Th2-allergic immune response.47

We report a positive correlation between IL-17A level and both TG and LDL-C levels, while IL-17A was negatively correlated to HDL-C level among AR patients. These findings are in line with.26 This could be explained by the fact that dyslipidemia causesTh2 and Th17 polarization and cytokines release as (IL-4, IL-17) with decreased production of IL-10. These cytokines disturbance is related to chronic inflammation that is common to both atopic predisposition and dyslipidemia6,46,48 Similarly, Vinding et al found that triglyceride levels were associated with increased risk of aeroallergen sensitization, which is one cause of AR.18

Furthermore, we found significant positive correlation between IL-17A and AR severity assessed by VAS score. IL-17 is a pro-inflammatory cytokine which in turn explains its role in increasing the severity of AR symptoms. This is consistent with many other studies.49 Also, Nieminen et al50 showed that serum IL-17A levels and allergen-induced IL-17A messenger RNA expression correlate with symptom severity, as assessed via a VAS score and symptom medication score, respectively. In addition, Lu et al51 reported significant correlations between AR symptoms and the expression of IL-17 in nasal mucosa and peripheral blood.

A study by Shahsavan et al52 found that patients with moderate to severe persistent AR demonstrated significantly greater IL-22 and IL-17A production than healthy controls, suggesting that the development of persistent AR is influenced by these cytokines. A correlation was found between IL-22 and IL-17A serum levels, along with the mean number of IL-22 and IL-17A positive cells in the nasal mucosa, and specific IgE levels, nasal eosinophil count, and total nasal symptom score.

The results of these studies are partially in conflict with Amin et al,53 who found no correlation between IL-17 and the patients symptom scores, although AR patients have significant higher serum levels of IL-17 than controls.

In our study, we did not report a correlation between IL-17 and total IgE. Huang et al,45 documented that IL-17 level was positively related to the level of total IgE, and the serum level of IL-17 and IL-23 in the AR patients were markedly higher than those in healthy subjects.

We are aware that one of the limitations of the current study is the small sample size of the study population, and large-scale multicenter studies should be performed to further elucidate the importance of measuring serum lipid profile in AR patients, and including pediatrics where AR is more prevalent. The disease duration of AR was not reported in the current study. In addition, longitudinal studies might aid in a better understanding of the causal relationship between dyslipidemia and AR, to determine whether AR is preceded by dyslipidemia or the other way round. The role of cytokines as IL-17A as a biomarker of AR severity and its role in dyslipidemia should be further elucidated. Furthermore, early detection of dyslipidemia in AR patients may help in the prevention of long-term future cardiovascular morbidity and mortality in AR patients.

Measuring of serum lipid profile and IL-17A in AR patients could be a potential indicator of severe disease, and future research ought to explore the impact of timely treatment of dyslipidemia on severity of AR and QoL of patients.

The research ethics committee of Zagazig University approved the study (IRB number 6222-25-6-2020), and an informed verbal consent was obtained from all participants.

We thank all patients who participated in the study.

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

The authors report no conflicts of interest in this work.

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7. Hu X, Wang Y, Hao LY, et al. Sterol metabolism controls TH17 differentiation by generating endogenous ROR agonists. Nat Chem Biol. 2015;11(2):141147. doi:10.1038/nchembio.1714

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