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Immunology

The science and medicine of human immunology – Science Magazine

Immunology through a human lens

The coronavirus disease 2019 (COVID-19) pandemic has underscored the critical need to better understand the human immune system and how to unleash its power to develop vaccines and therapeutics. Much of our knowledge of the immune system has accrued from studies in mice, yet vaccines and drugs that work effectively in mice do not always translate into humans. Pulendran and Davis review recent technological advances that have facilitated the study of the immune system in humans. They discuss new insights and how these can affect the development of drugs and vaccines in the modern era.

Science, this issue p. eaay4014

The mammalian immune system is a remarkable sensory system for the detection and neutralization of pathogens. History is replete with the devastating effects of plagues, and the coronavirus disease 2019 (COVID-19) pandemic is a defining global health crisis of our time. Although the development of effective vaccines has saved many lives, the basic workings of the immune system are complex and require the development of animal models, such as inbred mice. Indeed, research in mice has been enormously productive, and the tremendous insights gleaned have resulted in many Nobel prizes and other accolades. However, past results are not necessarily a reliable guide to the future, and a notable limitation of animal models has been their failure to accurately model some human diseases and their inability to predict human immune responses in many cases. With regard to inbred mice, which have been the principal model of choice for immunology, this is likely due to the compromises that were necessary to create a more tractable and reproducible system for experimentation, such as genetic uniformity and lack of pathogen exposure, as well as the fact that mice are evolutionarily quite distinct. These considerations suggest that direct studies of the human immune system are likely to be extremely rewarding, both from a scientific and a medical perspective.

In the past decade there has been an explosion of new approaches and technologies to explore the human immune system with unprecedented precision. Insights into the human immune response to vaccination, cancers, and viral infections such as COVID-19 have come from high-throughput omics technologies that measure the behavior of genes, mRNA (single-cell transcriptomics), proteins (proteomics), metabolites (metabolomics), cells (mass cytometry), and epigenetic modifications (ATAC-seq), coupled with computational approaches.

Sydney Brenner remarked in 2008, We dont have to look for a model organism anymore. Because we are the model organisms. We propose that studying the immune system in humans, who are genetically diverse and afflicted by a multitude of diseases, offers both a direct link to medicine (i.e., translation) and the very real prospect of discovering fundamentally new human biology. New approaches and technology are now making this area much more approachable, but profiling immunity in humans is but the first step. Computational mining of the data and biological validation in animal models or human organoids are essential next steps, in an iterative cycle that seeks to bridge fundamental and applied science, as well as mouse and human immunology, in a seamless continuum of scientific discovery and translational medicine. This will represent a new paradigm for accelerating the development of vaccines and therapeutics.

Systems biology techniques can be used to probe the human immune response to viral infections and can define molecular signatures that predict disease severity and illuminate the underlying mechanisms of disease.

Although the development of effective vaccines has saved countless lives from infectious diseases, the basic workings of the human immune system are complex and have required the development of animal models, such as inbred mice, to define mechanisms of immunity. More recently, new strategies and technologies have been developed to directly explore the human immune system with unprecedented precision. We discuss how these approaches are advancing our mechanistic understanding of human immunology and are facilitating the development of vaccines and therapeutics for infection, autoimmune diseases, and cancer.

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The science and medicine of human immunology - Science Magazine

Immunology

Pandion Therapeutics to Participate in Panel Discussion at Stifel 2020 Immunology & Inflammation Virtual Summit – BioSpace

WATERTOWN, Mass., Sept. 24, 2020 (GLOBE NEWSWIRE) -- Pandion Therapeutics, Inc. (Nasdaq: PAND), a clinical-stage biotechnology company developing novel therapeutics designed to address the unmet needs of patients living with autoimmune diseases, today announced that Rahul Kakkar, M.D., Chief Executive Officer of Pandion Therapeutics, will participate in a panel discussion at the upcoming Stifel Immunology & Inflammation Summit on Thursday, October 1, 2020 at 3:00 p.m. ET.

A live audio webcast of the panel will be available on the Investors and News section of Pandion Therapeutics investor website at https://investors.pandiontx.com/. A replay of the webcast will be available shortly following the presentation.

About Pandion TherapeuticsPandion Therapeuticsis developing novel therapeutics designed to address the unmet needs of patients living with autoimmune diseases. Pandions TALON (Therapeutic Autoimmune reguLatOry proteiN) drug design and discovery platform enables the company to create a pipeline of product candidates using immunomodulatory effector modules, with the ability to also combine an effector module with a tissue-targeted tether module in a bifunctional format.Pandions lead product candidate PT101, a combination of an interleukin-2 mutein effector module with a protein backbone, is designed to selectively expand regulatory T cells systemically, without activating proinflammatory cells, such as conventional T cells and natural killer cells, is currently in a Phase 1a clinical trial. Pandion is continuing to develop and expand its library of effector and tether modules as part of its earlier-stage research and discovery pipeline. For more information, please visitwww.pandiontx.com.

For further information, please contact:

Media:Kathryn MorrisThe Yates Network914-204-6412kathryn@theyatesnetwork.com

Investors:Michelle AveryPandion Therapeuticsinvestors@pandiontx.com

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Pandion Therapeutics to Participate in Panel Discussion at Stifel 2020 Immunology & Inflammation Virtual Summit - BioSpace

Immunology

Study reveals higher incidence of immunology diseases in donor sperm-conceived adults – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 24 2020

Adults conceived through sperm donation reported higher frequencies of allergies, type 1 diabetes and other autoimmune conditions in a world-first study that examined the long term health outcomes of donor-conceived people.

The study was conducted by Flinders University's Caring Futures Institute, led by researcher Damian Adams, and published in the Journal of Developmental Origins of Health and Disease. It looked at 272 donor-conceived adult participants from around the world together with 877 who were conceived naturally.

Results revealed that for most health outcomes, donor sperm conceived adults reported no significant difference to participants born through natural conception.

However, donor sperm conceived adults had seven times more type 1 diabetes diagnoses than naturally conceived adults, together with double the incidence of thyroid disease, acute bronchitis and sleep apnoea; and a 45% incidence of allergies compared to 35% in the naturally conceived population.

Mr Adams says most of the health conditions reported by donor conceived people had an immunological basis, suggesting an alteration to their immunological systems.

What may potentially be driving this is the maternal complication of preeclampsia, which has increased incidences associated with the use of donated gametes (sex cells).

Preeclampsia is an extremely serious condition that is mediated by the immune system. Research has shown that children born from a pregnancy complicated by preeclampsia have altered epigenetic profiles including links with an altered immune system."

Damian Adams, Researcher, Flinders University

Mr Adams is a PhD candidate at Flinders University, whose interest in the health outcomes of donor-conceived people was sparked by vast knowledge gaps in the area.

His supervisors include Flinders University Professor Sheryl de Lacey, who has a clinical background in infertility and assisted reproductive technology.

She says the use of donor gametes has been cloaked in secrecy and abetted by anonymity, with pregnancies assumed to be no different to natural conceptions.

"Being aware of an increased risk of pre-eclampsia in pregnancy and the implications for children in adulthood holds the potential to empower women beyond their pregnancy," Professor de Lacey says.

"For parents, this unique study provides important information that informs their decision of whether to disclose conception means to their child, and to choose the health care they receive.

For donor-conceived people, having this information may improve vigilance in preventative health behaviors."

Mr Adams says donor-conceived people are a hard to reach population, with research consistently showing that the majority do not know they were conceived by sperm donation.

"We had to implement six different recruitment strategies to attract the sample size we achieved," he says.

The majority of participants were from Australia, the United States, the United Kingdom, Belgium and the Netherlands.

Those conceived by donor or through natural conception were matched for age, sex, height, smoking habits, alcohol consumption, exercise and fertility.

"This study was preceded by our systematic review of the literature, where we noted a dearth of studies investigating the perinatal and long-term health outcomes of donor sperm treatments, despite the technique being used for almost 140 years," Mr Adams says.

Source:

Journal reference:

Adams, D.H., et al. (2020) Self-reported physical health status of donor sperm-conceived adults. Journal of Developmental Origins of Health and Disease. doi.org/10.1017/S204017442000080X.

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Study reveals higher incidence of immunology diseases in donor sperm-conceived adults - News-Medical.Net

Immunology

Catalyst Biosciences to Present at the Stifel Immunology and Inflammation Summit – Yahoo Finance

TipRanks

Markets are volatile, there can be no doubt. So far this month, the S&P 500 has fallen 9% from its peak. The tech-heavy NASDAQ, which had led the gainers all summer, is now leading the on the fall, having lost 11% since September 2. The three-week tumble has investors worried that we may be on the brink of another bear market.The headwinds are strong. The usual September swoon, the upcoming election, doubts about another round of economic stimulus all are putting downward pressure on the stock markets.Which doesnt mean that there are no opportunities. As the old saw goes, Bulls and bears can both make money, while the pigs get slaughtered. A falling market may worry investors, but a smart strategy can prevent the portfolio from losing too much long-term value while maintaining a steady income. Dividend stocks, which feed into the income stream, can be a key part of such a strategy.Using the data available in the TipRanks database, weve pulled up three stocks with high yields from 7% to 11%, or up to 6 times the average dividend found on the S&P 500 index. Even better, these stocks are seen as Strong Buys by Wall Streets analysts. Lets find out why.Williams Companies (WMB)We start with Williams Companies, an Oklahoma-based energy company. Williams controls pipelines connecting Rocky Mountain natural gas fields with the Pacific Northwest region, and Appalachian and Texan fields with users in the Northeast and transport terminals on the Gulf Coast. The companys primary operations are the processing and transport of natural gas, with additional ops in crude oil and energy generation. Williams handles nearly one-third of all US commercial and residential natural gas use.The essential nature of Williams business really, modern society simply cannot get along without reliable energy sources has insulated the company from some of the economic turndown in 1H20. Quarterly revenues slid from $2.1 billion at the end of last year to $1.9 billion in Q1 and $1.7 billion in Q2. EPS in the first half was 26 cents for Q1 and 25 cents for Q2 but this was consistent with EPS results for the previous three quarters. The generally sound financial base supported the companys reliable dividend. Williams has been raising that payment for the past four years, and even the corona crisis could not derail it. At 40 cents per common share, the dividend annualizes to $1.60 and yields an impressive 7.7%. The next payment is scheduled for September 28.Truist analyst Tristan Richardson sees Williams as one of the midstream sectors best positioned companies.We continue to look to WMB as a defensive component of midstream and favor its 2H prospects as broader midstream grasps at recovery Beyond 2020 we see the value proposition as a stable footprint with free cash flow generation even in the current environment. We also see room for incremental leverage reduction throughout our forecast period on scaled back capital plans and even with the stable dividend. We look for modestly lower capex in 2021, however unlike more G&P oriented midstream firms, we see a project backlog in downstream that should support very modest growth, Richardson noted.Accordingly, Richardson rates WMB shares as a Buy, and his $26 price target implies a 30% upside potential from current levels. (To watch Richardsons track record, click here)Overall, the Strong Buy analyst consensus rating on WMB is based on 11 Buy reviews against just a single Hold. The stocks current share price is $19.91 and the average price target is $24.58, making the one-year upside potential 23%. (See WMB stock analysis on TipRanks)Magellan Midstream (MMP)The second stock on our list is another midstream energy company, Magellan. This is another Oklahoma-based firm, with a network of assets across much of the US from the Rocky Mountains to the Mississippi Valley, and into the Southeast. Magellans network transports crude oil and refined products, and includes Gulf Coast export shipping terminals.Magellan's total revenues rose sequentially to $782.8 in Q1, and EPS came in at $1.28, well above the forecast. These numbers turned down drastically in Q2, as revenue fell to $460.4 million and EPS collapsed to 65 cents. The outlook for Q3 predicts a modest recovery, with EPS forecast at 85 cents. The company strengthened its position in the second quarter with an issue of 10-year senior notes, totaling $500 million, at 3.25%. This reduced the companys debt service payments, and shored up liquidity, making possible the maintenance of the dividend.The dividend was kept steady at $1.0275 per common share quarterly. Annualized, this comes to $4.11, a good absolute return, and gives a yield of 11.1%, giving MMP a far higher return than Treasury bonds or the average S&P-listed stock.Well Fargo analyst Praneeth Satish believes that MMP has strong prospects for recovery. [We] view near-term weakness in refined products demand as temporary and recovering. In the interim, MMP remains well positioned given its strong balance sheet and liquidity position, and ratable cash flow stream Satish goes on to note that the dividend appears secure for the near-term: The company plans to maintain the current quarterly distribution for the rest of the year.In line with this generally upbeat outlook, Satish gives MMP an Overweight (i.e. Buy) rating, and a $54 price target that implies 57% growth in the coming year. (To watch Satishs track record, click here)Net net, MMP shares have a unanimous Strong Buy analyst consensus rating, a show of confidence by Wall Streets analyst corps. The stock is selling for $33.44, and the average price target of $51.13 implies 53% growth in the year ahead. (See MMP stock analysis on TipRanks)Ready Capital Corporation (RC)The second stock on our list is a real estate investment trust. No surprise finding one of these in a list of strong dividend payers REITs have long been known for their high dividend payments. Ready Capital, which focuses on the commercial mortgage niche of the REIT sector, has a portfolio of loans in real estate securities and multi-family dwellings. RC has provided more than $3 billion in capital to its loan customers.In the first quarter of this year, when the coronavirus hit, the economy turned south, and business came to a standstill, Ready Capital took a heavy blow. Revenues fell by 58%, and Q1 EPS came in at just one penny. Things turned around in Q2, however, after the company took measures including increasing liquidity, reducing liabilities, and increasing involvement in government-sponsored lending to shore up business. Revenues rose to $87 million and EPS rebounded to 70 cents.In the wake of the strong Q2 results, RC also started restoring its dividend. In Q1 the company had slashed the payment from 40 cents to 25 cents; in the most recent declaration, for an October 30 payment, the new dividend is set at 30 cents per share. This annualizes to $1.20 and gives a strong yield of 9.9%.Crispin Love, writing from Piper Sandler, notes the companys success in getting back on track.Given low interest rates, Ready Capital had a record $1.2B in residential mortgage originations versus our $1.1B estimate. Gain on sale margins were also at record levels. We are calculating gain on sale margins of 3.7%, up from 2.4% in 1Q20, Love wrote.In a separate note, written after the dividend declaration, Love added, We believe that the Board's actions show an increased confidence for the company to get back to its pre-pandemic $0.40 dividend. In recent earnings calls, management has commented that its goal is to get back to stabilized earnings above $0.40, which would support a dividend more in-line with pre-pandemic levels.To this end, Love rates RC an Overweight (i.e. Buy) along with a $12 price target, suggesting an upside of 14%. (To watch Loves track record, click here)All in all, Ready Capital has a unanimous Strong Buy analyst consensus rating, based on 4 recent positive reviews. The stock has an average price target of $11.50, which gives a 9% upside from the current share price of $10.51. (See RC stock analysis on TipRanks)To find good ideas for dividend stocks trading at attractive valuations, visit TipRanks Best Stocks to Buy, a newly launched tool that unites all of TipRanks equity insights.Disclaimer: The opinions expressed in this article are solely those of the featured analysts. The content is intended to be used for informational purposes only. It is very important to do your own analysis before making any investment.

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Catalyst Biosciences to Present at the Stifel Immunology and Inflammation Summit - Yahoo Finance

Immunology

TL1A and its receptor could reduce fibrosis and tissue remodeling in patients with severe lung disease – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 25 2020

Your lungs and airways need to be stretchy, sort of like balloons. Take a big breath, and they'll open right up.

Damaged lungs can't open properly. Patients with asthma, idiopathic pulmonary fibrosis and systemic sclerosis suffer from fibrosis and tissue remodeling, where a build-up of tissue and immune cells, and proteins that form a glue-like substance, keep the airways from expanding. As fibrosis gets worse, taking a breath feels like blowing up a balloon filled with concrete.

In a new study, researchers at La Jolla Institute for Immunology (LJI) report that a protein called TL1A drives fibrosis in several mouse models, triggering tissue remodeling, and making it harder for lungs and airways to function normally.

"Our new study suggests that TL1A and its receptor on cells could be targets for therapeutics aimed at reducing fibrosis and tissue remodeling in patients with severe lung disease," says LJI Professor Michael Croft, Ph.D., director of scientific affairs at LJI and senior author of the new study in The Journal of Immunology.

Croft's laboratory is focused on understanding the importance of a family of proteins, called tumor necrosis factors (TNF) and tumor necrosis factor receptors (TNFR), in inflammatory and autoimmune diseases. By investigating these molecules, researchers hope to track down the root causes of inflammation and stop tissue damage before it's too late.

Previous research had shown that a TNF protein called TL1A can act on immune cells involved in allergic reactions and drive those immune cells to make inflammatory molecules. The Croft Lab wondered-;if TL1A leads to inflammation, could it contribute to fibrosis in the lungs?

For the new study, Croft and his colleagues used genetic and therapeutic interventions, tissue staining, and fluorescence imaging techniques to study protein interactions in mouse models of severe asthma, idiopathic pulmonary fibrosis and systemic sclerosis. They first discovered that TL1A acts directly on a receptor on cells in the lungs and bronchial tubes, which leads to fibrosis and tissue remodeling.

We're all familiar with the idea of tissue remodeling. When a wound on the skin heals, the new area of skin is sometimes shiner, darker or tougher than the skin around it.

The tissue has been remodeled. When lungs and airways try to heal-;in response to an asthma attack, for example-; the cells in the area also change. The damaged area accumulates cells called fibroblasts, which make several glue-like proteins, including collagen. Too much collagen makes the lungs and airways less elastic-;and less functional.

As Croft describes it, tissue remodeling is like wound healing, "but wound healing that goes wrong and becomes so exaggerated that it blocks tissue from behaving in its normal way." With the new study, scientists now know that TL1A is driving this harmful remodeling in the lungs.

In addition to causing fibroblasts to make collagen, the researchers found that TL1A also helps fibroblasts to behave like smooth muscle cells.

A thin layer of smooth muscle cells naturally lines the bronchial tubes allowing them to dilate and constrict, but a thick layer of these smooth muscle cells-;that includes fibroblasts-;will keep the airways from expanding and contracting normally, making it even hard for a patient to breathe.

The scientists then studied lung tissue remodeling in mice that lacked the receptor for TL1A, called DR3, or were given a reagent that blocked TL1A activity. These mice showed less lung remodeling, less collagen deposition and reduced smooth muscle mass in the lungs.

These animal model data may support recent research in humans. Researchers have found that patients with severe asthma have excessive production of TL1A. This could explain why these patients are more vulnerable to lung fibrosis and remodeling.

This type of research needs to be expanded to really understand if there are subsets of patients with asthma or other inflammatory lung diseases who might express TL1A at higher levels than other patients-;which could potentially guide future therapies for targeting TL1A to reduce remodeling and fibrosis."

Michael Croft, PhD, Professor and Study Senior Author, Director of Scientific Affairs, La Jolla Institute for Immunology

Going forward, Croft and his team plan to investigate how the DR3 receptor is expressed on tissue cells and whether it is affected by other inflammatory factors. They also want to know how active TL1A is in human patients and how many inflammatory activities the protein might be responsible for.

Source:

Journal reference:

Herro, R., et al. (2020) TL1A Promotes Lung Tissue Fibrosis and Airway Remodeling. Journal of Immunology. doi.org/10.4049/jimmunol.2000665.

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TL1A and its receptor could reduce fibrosis and tissue remodeling in patients with severe lung disease - News-Medical.Net

Immunology

The Tisch Cancer Institute Earns Second Consecutive Designation from National Cancer Institute – Newswise

Newswise New York, NY (September 24, 2020) The Tisch Cancer Institute at Mount Sinai (TCI) has been awarded $13 million as part of the renewal of its National Cancer Institute Cancer Center Designation, a prestigious distinction that is based on scientific excellence, robust clinical research, and beneficial community impact. The National Cancer Institute rated TCIs application as outstanding.

The five-year redesignation awardthe Institutes second consecutive designationwill support research programs and facilities, promote collaborative translational cancer research in a coordinated manner, and help disseminate cancer research findings to the community. The funding complements $53 million in current cancer research grants earned by TCI investigators.

The strategic plan that helped lead to the redesignation this year included cutting-edge clinical research developed by teams from several disciplines, allowing TCI to provide personalized care to the New York City metro areas diverse communities. Four areas in which TCI researchers and physicians excel, and which contributed to the redesignation, include:

TCI was first named an NCI-designated cancer center in 2015. Since then, the recruitment of leaders in cancer genomics, lung cancer, cancer immunology, and clinical research, and the exponential growth of clinical trials originated by Mount Sinai physicians, has helped bolster the cancer centers national prominence and continued to bring cutting-edge research from the lab to the bedside of Mount Sinai patients.

The NCI redesignation recognizes our plan to maximize our ability to make an impact in our community and at the national level over the next five years, expanding on our successes in four key areas: cancer immunology, cancer mechanisms, cancer clinical investigation, and cancer prevention and control, said Ramon Parsons, MD, PhD, Director of The Tisch Cancer Institute at Mount Sinai, Ward-Coleman Chair in Cancer Research, and Chair of Oncological Sciences at the Icahn School of Medicine at Mount Sinai. Our patients are the beneficiaries of our commitment to advancing scientific research in cancer and harnessing our findings into new therapies and prevention initiatives.

Some achievements in the four key areas include:

Our physicians have built up a repertoire of investigator-initiated trials and novel clinical research studies, which contributed to this redesignation and has become a strength of The Tisch Cancer Institute, said William K. Oh, MD, Deputy Director of The Tisch Cancer Institute, Chief of the Division of Hematology and Medical Oncology at the Mount Sinai Health System, and the Ezra M. Greenspan, MD, Professor in Clinical Cancer Therapeutics at the Icahn School of Medicine at Mount Sinai. Another strength that sets us apart is our research on cancer in World Trade Center responders, due to our unique position of having a monitoring program at Mount Sinai. Our research has led to insights into how inflammation leads to cancer as well as which cancers should be investigated in this vulnerable population.

The Tisch Cancer Institute at Mount Sinai investigates real-world, complex medical problems and solves them with teams of scientists and physicians that successfully integrate many disciplines, said Dennis S. Charney, MD, Anne and Joel Ehrenkranz Dean of the Icahn School of Medicine at Mount Sinai and President for Academic Affairs of the Mount Sinai Health System. The NCI redesignation underscores our exceptional leadership, extensive research facilities, and an institution-wide commitment to research with a focus on identifying and combatting disparities so that all patients receive the best care possible.

About the Mount Sinai Health System

The Mount Sinai Health System is New York City's largest academic medical system, encompassing eight hospitals, a leading medical school, and a vast network of ambulatory practices throughout the greater New York region. Mount Sinai is a national and international source of unrivaled education, translational research and discovery, and collaborative clinical leadership ensuring that we deliver the highest quality carefrom prevention to treatment of the most serious and complex human diseases. The Health System includes more than 7,200 physicians and features a robust and continually expanding network of multispecialty services, including more than 400 ambulatory practice locations throughout the five boroughs of New York City, Westchester, and Long Island. The Mount Sinai Hospital is ranked No. 14 onU.S. News & World Report's"Honor Roll" of the Top 20 Best Hospitals in the country and the Icahn School of Medicine as one of the Top 20 Best Medical Schools in country. Mount Sinai Health System hospitals are consistently ranked regionally by specialty and our physicians in the top 1% of all physicians nationally byU.S. News & World Report.

For more information, visithttps://www.mountsinai.orgor find Mount Sinai onFacebook,TwitterandYouTube.

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The Tisch Cancer Institute Earns Second Consecutive Designation from National Cancer Institute - Newswise

Genetics

Scientists discover genetic and immunologic underpinnings of some cases of severe COVID-19 – National Institutes of Health

Media Advisory

Thursday, September 24, 2020

New findings by scientists at the National Institutes of Health and their collaborators help explain why some people with COVID-19 develop severe disease. The findings also may provide the first molecular explanation for why more men than women die from COVID-19.

The researchers found that more than 10% of people who develop severe COVID-19 have misguided antibodiesautoantibodiesthat attack the immune system rather than the virus that causes the disease. Another 3.5% or more of people who develop severe COVID-19 carry a specific kind of genetic mutation that impacts immunity. Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses. Whether these proteins have been neutralized by autoantibodies orbecause of a faulty genewere produced in insufficient amounts or induced an inadequate antiviral response, their absence appears to be a commonality among a subgroup of people who suffer from life-threatening COVID-19 pneumonia.

These findings are the first published results from the COVID Human Genetic Effort, an international project spanning more than 50 genetic sequencing hubs and hundreds of hospitals. The effort is co-led by Helen Su, M.D., Ph.D., a senior investigator at the National Institute of Allergy and Infectious Diseases (NIAID), part of NIH; and Jean-Laurent Casanova, M.D., Ph.D., head of the St. Giles Laboratory of Human Genetics of Infectious Diseases at The Rockefeller University in New York. Major contributions were made by Luigi Notarangelo, M.D., chief of the NIAID Laboratory of Clinical Immunology and Microbiology (LCIM); Steven Holland, M.D., director of the NIAID Division of Intramural Research and senior investigator in the NIAID LCIM; clinicians and investigators in hospitals in the Italian cities of Brescia, Monza and Pavia, which were heavily hit by COVID-19; and researchers at the Uniformed Services University of the Health Sciences in Bethesda, Maryland.

The wide variation in the severity of disease caused by SARS-CoV-2, the virus behind COVID-19, has puzzled scientists and clinicians. SARS-CoV-2 can cause anything from a symptom-free infection to death, with many different outcomes in between. Since February 2020, Drs. Su and Casanova and their collaborators have enrolled thousands of COVID-19 patients to find out whether a genetic factor drives these disparate clinical outcomes.

The researchers discovered that among nearly 660 people with severe COVID-19, a significant number carried rare genetic variants in 13 genes known to be critical in the bodys defense against influenza virus, and more than 3.5% were completely missing a functioning gene. Further experiments showed that immune cells from those 3.5% did not produce any detectable type I interferons in response to SARS-CoV-2.

Examining nearly 1,000 patients with life-threatening COVID-19 pneumonia, the researchers also found that more than 10% had autoantibodies against interferons at the onset of their infection, and 95% of those patients were men. Biochemical experiments confirmed that the autoantibodies block the activity of interferon type I.

Q Zhang et al. Inborn errors of type I IFN immunity in patients with life-threatening COVID-19. Science DOI: 10.1126/science.abd4570 (2020).

P Bastard et al. Auto-antibodies against type I IFNs in patients with life-threatening COVID-19. Science DOI: 10.1126/science.abd4585 (2020).

NIAID Director Anthony S. Fauci, M.D., NIAID Senior Investigator Helen C. Su, M.D., Ph.D., and Luigi Notarangelo, M.D., chief of the NIAID Laboratory of Clinical Immunology and Microbiology, are available for interviews.

To schedule interviews, please contact NIAID Office of Communications, (301) 402-1663, NIAIDNews@niaid.nih.gov.

NIAID conducts and supports research at NIH, throughout the United States, and worldwide to study the causes of infectious and immune-mediated diseases, and to develop better means of preventing, diagnosing and treating these illnesses. News releases, fact sheets and other NIAID-related materials are available on the NIAID website.

About the National Institutes of Health (NIH):NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.

NIHTurning Discovery Into Health

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Scientists discover genetic and immunologic underpinnings of some cases of severe COVID-19 - National Institutes of Health

Genetics

Zelis and Concert Genetics Launch Genetic Testing Claim Editing Solution – Business Wire

BEDMINSTER, N.J. & NASHVILLE, Tenn.--(BUSINESS WIRE)--Zelis, the healthcare industrys leading claims cost and payments optimization platform with superior technology and solutions to price, pay and explain claims, and Concert Genetics, a technology company dedicated to advancing precision medicine, have launched a claim editing solution for the complex and rapidly-growing area of genetic testing.

The solution embeds Concerts claim editing capabilities, which are powered by robust genetic testing market data and machine learning, into Zelis existing claim editing platform. This leading-edge platform already contains more than 18 million edits sourced to national coding standards. The partnership adds specialized content in genetic testing that other platforms lack, enabling Zelis and Concert to improve coding and billing accuracy of these complex and ambiguous genetic test claims before they are paid.

Our clients are experiencing higher costs due to the complexity of managing the variability of genetic testing codes and volume of new tests entering the market, said R. Andrew Eckert, Zelis CEO. Combining our payment integrity expertise with Concerts precision technology will enable us to proactively identify inaccurate claims and continue to support our clients with innovative solutions to reduce costs.

This solution comes at a critical time, as the availability and demand for genetic tests grow with the global genetic testing market expected to reach $17.6 billion by 2025, from $7.5 billion in 2017.1 Additionally, the total number of available genetic testing products has surpassed 150,000, up from around 10,000 in 2012. Meanwhile, much of the growth in volume is represented by multi-gene panel tests, which are particularly difficult for health plans to process in an efficient and accurate way because they are billed using multiple billing codes in widely varying combinations. Some categories of genetic tests are billed in thousands of different code combinations.

The pace of advancement in the science and clinical application of genetics is remarkable, and the healthcare system has had difficulty keeping up, said Rob Metcalf, CEO of Concert Genetics. Concert has assembled the data and digital infrastructure to enable transparency, connectivity, and value in this space, and we are pleased to partner with Zelis to make our technology available to its clients.

A key enabler of this claim editing solution is its ability to match complex claims with multiple billing codes back to its catalog of tests on the market. The combined solution is available to Zelis clients effective immediately.

About Zelis

Zelis is the healthcare industrys leading claims cost and payments optimization platform with superior technology and solutions to price claims, pay claims and explain claims, all at enterprise scale on a claim-by-claim basis. Zelis leverages proprietary technology, robust analytics, extensive payment and provider networks, and innovative claim savings channels to deliver to the industry superior administrative and medical cost savings. Zelis was founded on a belief that there is a better way to determine the cost of a healthcare claim, manage payment related data, and make the claim payment. Zelis provides the industrys only comprehensive, integrated platform to take a claim through the entire pre-payment to payments lifecycle. Zelis ~1000 associates serve more than 700 payor clients, including the top-5 national health plans, Blues plans, regional health plans, TPAs and self-insured employers, and more than 1.5 million providers. Zelis delivers more than $5B of claims savings, $50B of provider payments and 500 million payment data communications annually.

About Concert Genetics

Concert Genetics is a software and managed services company that advances precision medicine by providing the digital infrastructure for reliable and efficient management of genetic testing. Concerts market-leading genetic test order management platform leverages a proprietary database of the U.S. clinical genetic testing market today more than 150,000 testing products and genetic testing claims from more than 100 million lives. Learn more at http://www.ConcertGenetics.com.

1 Allied Market Research report, Genetic Testing Market by Type (Predictive Testing, Carrier Testing, Prenatal & Newborn Testing, Diagnostic Testing, Pharmacogenomic Testing, and Others), Technology (Cytogenetic Testing, Biochemical Testing, and Molecular Testing), and Application (Chromosome Analysis, Genetic Disease Diagnosis, Cardiovascular Disease Diagnosis, and Others): Global Opportunity Analysis and Industry Forecast, 20182025

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Genetics

NIH researchers find genetic link in patients with severe COVID-19 – fox6now.com

United launches rapid COVID-19 testing program for some travelers

United Airlines plans to offer COVID-19 tests for passengers flying from San Francisco International Airport to Hawaii.

LOS ANGELES - Scientists at the National Institutes of Health (NIH) say they have found how genetics play a critical role in who develops severe cases of COVID-19 and why more men than women die from the illness.

Much is still being learned about the novel coronavirus that has claimed the lives of more than 200,000 people in the U.S. Nearly 1 million deaths have been recorded worldwide to date, according to data tracked by Johns Hopkins University.

Researchers have rushed to study the unpredictable and wide variations in illness severity that the virus causes in different people. Determining whether a genetic factor contributes to the virus severity and health outcomes of COVID-19 patients is highly important for researchers to develop a solution to the crisis.

Results published as part of the COVID Human Genetic Effort, an international project consisting of more than 50 genetic sequencing hubs and hundreds of hospitals, found that more than 10% of people who develop a severe case of the coronavirus have misguided antibodies which attack the immune system.

FILE - A medical laboratory scientist runs a clinical test in the Immunology lab at UW Medicine looking for antibodies against SARS-CoV-2. (Photo by Karen Ducey/Getty Images)

Researchers found that another 3.5% of people who develop severe COVID-19 carry a specific genetic mutation which negatively impacts immunity from the disease.

Consequently, both groups lack effective immune responses that depend on type I interferon, a set of 17 proteins crucial for protecting cells and the body from viruses," according to a news release by the NIH.

The researchers discovered that among nearly 660 people with severe COVID-19, a significant number carried rare genetic variants in 13 genes known to be critical in the bodys defense against influenza virus, and more than 3.5% were completely missing a functioning gene, the NIH wrote.

The health agency said the absence of these proteins appear to be common among a subgroup of people who are at risk of life-threatening effects of COVID-19.

After examining 1,000 patients with life-threatening pneumonia caused by the coronavirus, researchers found that 10% of patients had the misguided antibodies, otherwise known as autoantibodies, which defended against the interferon proteins needed to protect the cells. Of those patients with harmful antibodies, 95% were men.

RELATED: Could your symptoms be COVID-19? The signs range from mild to severe

Health officials say that becoming infected with COVID-19 can lead to a wide variety of symptoms, ranging from mild to severe. The most common symptoms are fever, a dry cough, shortness of breath and fatigue.

But as the months-old virus continues its spread, additional symptoms are being identified and they can be unpredictable.

The U.S. Centers for Disease Control and Prevention highlights 11 key symptoms of COVID-19 on its website:

Fever or chillsCoughShortness of breath or difficulty breathingFatigueMuscle or body achesHeadacheNew loss of taste or smellSore throatCongestion or runny noseNausea or vomitingDiarrhea

The agency notes that the list does not include all possible symptoms of COVID-19, and said that it would continue to update the list as more becomes known about the virus.

Kelly Taylor Hayes contributed to this story.

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NIH researchers find genetic link in patients with severe COVID-19 - fox6now.com

Genetics

Researchers elucidate the impact of genetic mutations in cocaine addiction – News-Medical.Net

Reviewed by Emily Henderson, B.Sc.Sep 26 2020

Cocaine addiction is a chronic disorder with a high rate of relapse for which no effective treatment is currently available.

Scientists from the Institut Pasteur, the CNRS, Inserm and the Paris Public Hospital Network (AP-HP) recently demonstrated that two gene mutations involved in the conformation of nicotinic receptors in the brain appear to play a role in various aspects of cocaine addiction. The results of the study were published in Progress in Neurobiology.

There are approximately 18 million users worldwide, and cocaine is implicated in more than 50% of overdose deaths in the United States and 25% in France. It is also one of the only drugs for which there is no approved pharmacological treatment.

Cocaine acts primarily in the brain by blocking the dopamine transporter, thereby increasing the concentration of this "pleasure" molecule in the reward system. But cocaine can also act directly on the nicotinic receptors1 in the brain.

Several human genetics studies have recently suggested that a mutation in the gene encoding the 5 subunit of nicotinic receptors, hereafter referred to as '5SNP', already known to increase the risk of tobacco dependence,2 may conversely also confer "protection" against cocaine addiction.

This mutation is highly present in the general population (approximately 37% of Europeans and up to 43% of the Middle Eastern population carry it), so it is important to determine how it affects cocaine addiction and, more generally, to better understand the role of the 5 nicotinic subunit in the effects of cocaine.

Scientists of the Integrative Neurobiology of Cholinergic Systems Unit (Institut Pasteur/CNRS) began by evaluating the role of the 5 nicotinic subunit and the impact of the 5SNP mutation on various processes involved in the development of cocaine addiction in animal models. The results obtained were then used to characterize more specifically its impact on humans.

The scientists observed that the 5SNP mutation reduces the voluntary intake of cocaine upon first exposures.

These preclinical data suggest that the mutation protects against cocaine addiction by modulating an early phase in the addiction cycle."

Morgane Besson, Study Lead Author, Institut Pasteur

Working in collaboration with the Paris Public Hospital Network (AP-HP) and Inserm, the scientists then confirmed this significant effect in approximately 350 patients with cocaine addiction: those with the mutation exhibited a slower transition from first cocaine use to the emergence of signs of addiction.

At the same time, the authors showed that a total absence of the 5 nicotinic subunit increased the risk of relapse after withdrawal in preclinical models. This led the scientists to identify another mutation in another nicotinic subunit, 4, associated with a shorter time to relapse after withdrawal in addicted patients.

Taken together, these results elucidate the role played by both a highly frequent mutation in the 5 nicotinic subunit and the subunit itself in various stages of cocaine addiction. The research suggests that drugs modulating nicotinic receptors containing this 5 subunit could represent a novel therapeutic strategy for cocaine addiction.

Source:

Journal reference:

Forget, B., et al. (2020) Alterations in nicotinic receptor alpha5 subunit gene differentially impact early and later stages of cocaine addiction: a translational study in transgenic rats and patients. Progress in Neurobiology. doi.org/10.1016/j.pneurobio.2020.101898.

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Researchers elucidate the impact of genetic mutations in cocaine addiction - News-Medical.Net