All posts by medical

Immunology

Monitoring the immune system to fight COVID-19: CD4 status, lymphopenia, and infectivity – Science Magazine

30 April 2020

12:00 p.m. ET

Register now!

Andrea Cossarizza, M.D., Ph.D.

University of Modena and Reggio Emilia School of MedicineModena, Italy

Maurice OGorman, Ph.D., M.B.A., (D)ABMLI

Children's Hospital Los Angeles,Los Angeles, CA

Lishomwa (Lish) Ndhlovu, M.D., Ph.D.

Weill Cornell MedicineNew York, NY

Sean Sanders, Ph.D.

Science/AAASWashington, DC

The COVID-19 pandemic has struck the global population with unparalleled speed and ferocity. Researchers around the world are scrambling to learn about the biology, pathology, and genetics of SARS-CoV-2the novel coronavirus responsible for COVID-19while clinicians are seeking treatments, old and new, that might slow its infectivity and deadliness. In this webinar, we will explore what scientists are learning by using flow cytometry to study patients with COVID-19 in order to elucidate risk and disease severity. These experts are global leaders in cytometry and infectious disease, working on the frontlines of the COVID-19 outbreaks. They will provide concrete examples of how flow cytometry has been harnessed to provide key laboratory evidence that can be used in the fight against SARS-CoV-2 and COVID-19. Viewers will have the opportunity to put their questions to the expert panel during the live broadcast.

During the webinar, attendees will:

This webinar will last for approximately 60 minutes.

University of Modena and Reggio Emilia School of MedicineModena, Italy

Dr. Cossarizza completed his M.D. degree at the University of Padova in Italy before receiving a Ph.D. in oncology from the University of Modena and Reggio Emilia (UNIMORE) and the University of Bologna, also in Italy. After specializing in clinical pathology at UNIMORE, he obtained an associate professorship there. In 2005, he was appointed a professor in the international Ph.D. program at the University of Valencia in Spain, where he later became a research professor. In 2010, he became a full professor in pathology and immunology in the Faculty of Medicine at UNIMORE. He is a member of several editorial boards of international journals, and in 2016 was elected president of the International Society for Advancement of Cytometry. His primary research focus is identifying the molecular and cellular basis for the involvement of the immune system in diseases and infections, including HIV/AIDS and sepsis, as well as its role in pathophysiological conditions related to aging and neurodegeneration. Dr. Cossarizza has notable experience in the development and use of new flow cytometry approaches in immunological research.

Children's Hospital Los Angeles,Los Angeles, CA

Dr. OGorman earned his Masters and Ph.D. at the University of British Columbia before completing a postdoctoral fellowship at the University of North Carolina at Chapel Hill. He then joined the faculty at the Feinberg School of Medicine at Northwestern University, during which time he earned his MBA from Northwestern and served as vice chair of Pathology and Laboratory Medicine and director of Diagnostic Immunology and Flow Cytometry at Childrens Memorial Hospital in Chicago. He is currently chief of laboratory medicine, as well as director of the Clinical Lab and the Diagnostic Immunology and Flow Cytometry Laboratory at Childrens Hospital Los Angeles, and a professor of pathology and pediatrics at the Keck School of Medicine of the University of Southern California. Dr. OGormans research interests include immunopathogenesis of immune systemrelated disorders, investigation of immune mechanisms of immune suppression withdrawal in liver transplant patients, and the development of novel immune-related diagnostic laboratory tests. Additionally, he provides ad hoc reviews for multiple journals, including Cytometry,Journal of Leukocyte Biology, Journal of Immunological Methods, Clinical and Diagnostic Laboratory Immunology, and Archives of Pathology & Laboratory Medicine.

Weill Cornell MedicineNew York, NY

Dr. Ndhlovu is a professor of immunology at Weill Cornell Medicine in New York and principal investigator of the HIV and Emerging Pathogens Immunopathogenesis Laboratory in the Division of Infectious Diseases, also at Weill Cornell. A translational immunologist, he leads a research team dedicated to confronting the challenges of HIV and aging, with an emphasis on limiting disease complications and developing curative strategies. His program is now bringing the same urgency and focus to the COVID-19 pandemic, using both single-cell and epigenetic approaches to resolve molecular mechanisms regulating viral entry of SARS-CoV-2 infection across different tissues and cell types. His work seeks to identify therapeutic host targets and future therapies that reduce morbidity and mortality, and relieve the burden of this disease on society. Dr. Ndhlovu completed his undergraduate degree at the University of Zambia, his medical training at the University of Zambia Medical School, and his doctorate at Tohoku University School of Medicine in Japan.

Science/AAASWashington, DC

Dr. Sanders did his undergraduate training at the University of Cape Town, South Africa, and his Ph.D. at the University of Cambridge, UK, supported by the Wellcome Trust. Following postdoctoral training at the National Institutes of Health and Georgetown University, Dr. Sanders joined TranXenoGen, a startup biotechnology company in Massachusetts working on avian transgenics. Pursuing his parallel passion for writing and editing, Dr. Sanders joined BioTechniques as an editor, before joining Science/AAAS in 2006. Currently, Dr. Sanders is the Director and Senior Editor for Custom Publishing for the journal Science and Program Director for Outreach.

Go here to read the rest:
Monitoring the immune system to fight COVID-19: CD4 status, lymphopenia, and infectivity - Science Magazine

Immunology

Why we need more than just scientists to document the pandemic – RTE.ie

Opinion: we need to recognise that thiscrisis is as much about society and politicsas it is about virology, immunology and economics

Remarkable efforts have been made by a host of researchers in Ireland to address the Covid-19 crisis. These rangefrom studies in immunology to symptom-tracking technology, development of reagents for testingand a number of engineering solutions to address the need for ventilators and other essential equipment. The urgency and importance of this work is unquestionable and theimmediate requirement of reducing the death toll and the demands on hospitals remain of utmost importance. All of us will benefit from breakthroughs and successes as research continues.

But if we are to rise to the challenge presented by coronavirus, we must recognise that science and healthcare represent only one part of the equation. The rest of the story is essentially social, political and economic. In this trio of concerns, economic issues will dominate discussion as we attempt to navigate through a huge contraction of the economy, attended by massive job losses, business closures, and a remarkable strain on fiscal resources during a severe global downturn. Fortunately, institutions like the Central Bank and government departments have the resources of the ESRIto draw on foracademic expertise.

The risk is that in the midst of these demands and discussions we neglect the urgent responsibility to understand the social and political conditions underpinning the unfolding crisis. Only by coming to terms with these questions can we hope to avoid future calamities on this scale. The search for a vaccine constitutes a crucial remedy, but it will not in itself identify strengths and weaknesses in how governments have responded and how societies mobilise to confront a pandemic.

From RT Radio 1's The Business, a look at how the searchto find a coronavirus vaccine is progressing withFionnuala Keane (Health Research Board) and Dr Philip Cruz (Glaxo Smith Kline)

To date, major funding calls in Ireland have emerged from the Health Research Board in partnership with the Irish Research Council and Science Foundation Ireland. Some welcome scope existed in the former's call for "social and policy countermeasures", but we clearly need a much more wide-open approach that invites investigation of a series of complex, interrelated phenomena. Here is a list to be getting on with.

We have rich comparative information to harvest in comparing how different political systems have confronted the crisis. Techniques adopted in China to fight the virus, where it broke out, relied on an authoritarian government, even as that very system and lack of open reporting encouraged local officials not to indicate the gravity of the threat to public health. The lack of openness in Iran also deepened the disaster there.

South Korea, Taiwan and Germany have had success in mitigating the outbreakwith different models. In Europe, the Netherlands and Sweden have taken very different approaches by thus far refusing major lockdowns. We will need to examine and understandthe strength and weakness of their methods and how their social expectations and compliance have been managed.

From RT News, a report on mass burials in New York Cityamid record Covid-19 death rate

The staggering example of political dysfunction is the United States, now the world leader in terms of confirmed cases and the number of deaths. The Trump administration's undermining of agencies and departments, the lack of co-ordination between the states and the federal government, and opposition to healthcare reform have all played a part. Understanding these problems is vital because the countrys capacity to recover will determine the economic fate of many parts of the world.

In Ireland, the acute consequences of having two jurisdictions on the island have presented new challenges to co-operation and consistency. We have much to consider in how we coordinate our activities going forward since the virus is no respecter of Brexit and the border.

Public understanding of the Covid-19 crisis requires news media and reliable outlets for information. But this is the first pandemic in the era of social media, a wellspring of misinformation, rumour and supposed cures. The decisive role of trust and expertise demands renewed attention, even as crippling political attacks and polarisation have occurred, notably in the US. At the same time, the harvesting of data and systems of surveillance calls for much greater ethical reflection and assessment.

FromRT Radio 1'sDrivetime,Della Kilroy reports on how domestic abuse shelters are coping with social distancing restrictions

Social issues that come into play include not only the logistics of achieving isolation, but also the uneven effects of the lockdown. This is seen in differences in physical space, resources (such asinternet access and computer equipment) family structures (divorce and separation, people living alone etc), provisions for care, and the organisation of domestic space, not least to facilitate home schooling.

Social attitudes to ageing have taken on new significance as well as views about those occupying the frontline, not just in hospitals but in stores and delivery services - many of them in low paid positions. The arts have taken a backseat, by and large, but how have people accessed culture in the time of crisis and, perhaps more importantly, why do they continue to do so? More generally, what is the experience of virtualisation and its impact on work and social life? How can we write the history of the current response and how does it compareto past pandemics?

As the health crisis unfolds around the world, hard truths once again surface about the realities of our relationship with what is termed the Global South. When the disease escalates in Africa, what will be the response? Donald Trump's politically motivated halt on funding the WHO will have serious repercussions in this context.

From RT News, a report on the global condemnation of US president Donald Trump's decision to stop funding the WHO

Some attention has been given to the fate of those living in crowded migrant camps, and in direct provision centres in Ireland, but we have a new opportunity to study the effects of inequality, migration, and resources. We are simply lucky that Covid-19 is not as virulent as Ebola (which has an average rate of fatality of 50%). If coronavirus claimed lives at that rate, the losses inflicted by it would be extraordinary. Arguably, we failed to act to set proper systems in place because Ebola was largely confined to Africa. New lessons in racism abound at this time.

We all hope that a vaccine will be devised as soon as possible. Immunology, virology, and epidemiology are at the forefront of efforts. But if we don't get on top of the political and social challenges, we will be right back where we started the next time a crisis of this kind happens. Funding research is the first step in what needs to become a coordinated effortacross all the disciplines. Ireland can take the lead and show just how much this shared effort matters.

The views expressed here are those of the author and do not represent or reflect the views of RT

Read this article:
Why we need more than just scientists to document the pandemic - RTE.ie

Immunology

Researcher aims to promote diversity as member of global academy – UM Today

April 21, 2020

A UM faculty member who studies immune cells in her lab and promotes diversity in science has been selected for membership in a prestigious worldwide organization.

Dr. Janilyn Arsenio, assistant professor of internal medicine and immunology in the Max Rady College of Medicine, has been honoured with admission to the Global Young Academy (GYA).

Arsenio holds a Canada Research Chair in systems biology of chronic inflammation. She is one of four Canadians among this years 40 GYA inductees, who represent 30 countries.

The GYA brings together outstanding early-career researchers for international dialogue and collaboration. Members, who are typically in their 30s, are selected for their scientific excellence and commitment to service. Each member joins the academy for a term of five years.

The academy undertakes projects in a number of areas, from promoting science education and outreach to improving the research environment.

Its a group of young scientists who share a motivation to improve the scientific culture, Arsenio says. I applied because Im really passionate about promoting equity, diversity and inclusion in science.

As a visible minority academic woman in science, I feel a personal responsibility to advocate for that. Im a member of Canadian and American organizations like the Society for Canadian Women in Science and Technology and the Association for Women in Science, and this is an opportunity to interact on a more international level.

The Winnipeg-born Arsenio, who is of Filipino heritage, earned her bachelors degree in microbiology and her PhD in medical microbiology and infectious diseases at UM. She did four years of postdoctoral research, primarily in immunology, at the University of California San Diego before joining the UM faculty in 2017.

While in California, she learned techniques for analyzing the genetic material of individual cells. She brought that expertise to her lab at UMs Manitoba Centre for Proteomics and Systems Biology, making it the first lab in the province to enter the field of single-cell genomics.

Arsenio studies, at the molecular level, how immune cells behave in response to infection, chronic inflammation and disease. Were trying to understand how cells change to become functional protectors of the immune system, versus how their functions are lost during disease, she says.

The professor is vice-chair of Women in Science: Development, Outreach and Mentoring (WISDOM), a Manitoba organization based in the Rady Faculty of Health Sciences that works to address the under-representation of women in science, particularly in leadership. She also serves on the equity, diversity and inclusion committee of the Rady Faculty.

Arsenios previous honours include the American Association of Immunologists Young Investigator Award, which she received in 2016.

Her formal induction into the Global Young Academy was to have been at the academys 2020 conference and annual general meeting in India this June. Because of the COVID-19 crisis, the gathering has been converted to an e-conference. Hopefully, the new members will interact online, and we can meet in person at the 2021 meeting in Japan, Arsenio says.

Although she has studied infectious diseases, the scientist says its surreal to experience an outbreak on the scale of COVID-19. You learn about this during your training, but you never think that youll live through a pandemic, she says.

Like all lab scientists in the Rady Faculty, Arsenio has closed her lab and put her experiments on hold because of the pandemic.

Its very difficult to have to pause your research, she says. But were doing what we have to do for everyones well-being.

ALISON MAYES

Excerpt from:
Researcher aims to promote diversity as member of global academy - UM Today

Immunology

Markotic: 5620 serological tests to be used as aid in diagnostics – Croatia Week

Alemka Markotic(Photo: HINA/ Dario GRZELJ/ dag)

ZAGREB, April 21 (Hina) The director of the Hospital for Infectious Diseases in Zagreb, Alemka Markotic, has said that serological test kits have been ordered and that tests will be initially carried out on medical workers to see if any of them have recovered from COVID-19 infection unknowingly.

We have also received 5,620 testkits from the national civil protection authority and will use them as aid in diagnostics. We are planning even more tests to include a greater number of people in nursing homes. We are still looking at which sections of the population will be tested, Dr Markotic said in an interview with the Vecernji List daily of Tuesday.

She noted that social groups that turned out to be more prone to infection would be tested more frequently.

She also spoke of the Institute of Immunology and whether it could makeserological test kits.

The Institute of Immunology is our strategic institution. They did not produce diagnostic tests, but vaccines. That, however, does not mean that with some changes they could not produce certain diagnostic tests as well. In fact, a reform of the Institute of Immunology would be good. This institutions has been left to decline for years and many people have left. It will take a lot of energy to build plants, Markotic said.

Read the rest here:
Markotic: 5620 serological tests to be used as aid in diagnostics - Croatia Week

Immunology

High-throughput production of tetramer assay probes used for COVID-19 – Drug Target Review

The developers of a novel method to create immunological assay probes for screening T cells has leveraged their new protocol against COVID-19.

Researchers have developed a method that enables them to create libraries containing hundreds of molecular probes for tetramer assays in only days, whereas previous protocols required a week to produce a single probe. The team suggest their process opens up new opportunities for immunological research, development of cancer immunotherapies and assessment of immune responses from patients with COVID-19.

Tetramer assays are an immunological test used to detect and analyse the T cells in a blood sample. T cells each recognise and bind to a specific antigen like a viral protein and bind to them, identifying them to the immune system. However, where antibodies bind directly to antigens on the surface of a pathogen, T cells only bind to antigens expressed on the surface of antigen presenting cells, like macrophages and dendritic cells.

As a result, antibody assays are relatively simple and T-cell assays are more complex; requiring the probes for the latter to be formed of antigens incorporated into a molecular complex that mimics how they are presented in vivo, where they are bound to tetramers of major histocompatibility complex (MHC) proteins.

This diagram outlines a workflow for preparing and using a library of peptide-loaded MHC multimers for assessment of T cell repertoires in patient blood samples [credit: Overall et al., Nature Communications, 2020].

Corresponding author of the study published in Nature Communications, Nikolaos Sgourakis, assistant professor of chemistry and biochemistry at the University of California (UC) Santa Cruz has been studying how protein fragments are selected and bound to MHC proteins in cells for years, a process which requires molecular chaperones. The new protocol is based on his research which indicates that molecular chaperones can eject antigens that have low affinity for the MHC protein tetramers, in favour of antigens with higher affinity.

Sgourakis designed a placeholder peptide for use in preparing large quantities of pre-loaded MHC complexes. When incubated with a high-affinity antigen, the placeholder is displaced, a reaction that can be performed in a high-throughput system with large numbers of antigens.

Its a force multiplier, enabling us to perform these reactions at high throughput, Sgourakis said. A lot of groups are working on similar methodologies, all of which have their pros and cons. This technology has the advantage of using the same system that cells use naturally and we can combine it very elegantly with existing single-cell analytical tools.

The researchers originally used the new method to develop libraries of probes for assessing T-cell responses to neuroblastoma and designing cancer immunotherapies. However, since the emergence of COVID-19, the team have been exploring ways to apply the technology to address the challenges of the novel coronavirus. With a viral infection, there are many different fragments of the viral proteins that an infected cell can display and the researchers say it is important for drug design to determine which of these peptides elicit a strong immune response.

Based on the coronavirus genome, we can predict all the possible peptides, synthesise them, load them onto MHC tetramers and do a fishing expedition to find which ones are recognised by the T cells in blood samples from patients, Sgourakis explained. Certain peptides are immunodominant, ie, they steer the immune response and those are the ones we want to discover so we can potentially use them in a vaccine.

Sgourakis explained that the tetramer assays could also answer one of the biggest questions surrounding COVID-19: why is there so much variability in the severity of this disease?

According to Sgourakis, the approach can be used to compare the T-cell repertoires of different cohorts of patients. It is known that as people age their T-cell repertoire declines, resulting in a weaker immune response to pathogens, which may explain why older people are more vulnerable to COVID-19. Sgourakis said: We can use this technology to screen patients and see what the gaps are in their T-cell repertoires and maybe use this as a diagnostic for which patients will need more intensive treatment.

This research was in close collaboration with researchers at the New York Genome Center and the University of Pennsylvanias Childrens Hospital and Perelman School of Medicine, all US.

Related topicsAnalytical techniques, Assays, Cell-based assays, Disease research, Drug Development, Immunology, Protein, Proteomics, Research & Development, Screening, t-cells

More:
High-throughput production of tetramer assay probes used for COVID-19 - Drug Target Review

Immunology

Vivoryon Therapeutics Starts Development Program for Meprin Protease Inhibitors with Intended Therapeutic Use in Fibrosis, Cancer and Alzheimer’s…

HALLE (SAALE) / MUNICH and LEIPZIG, Germany, 16 April 2020 Vivoryon Therapeutics AG (Euronext Amsterdam: VVY, ISIN DE0007921835) announced today that the Company has entered into a research collaboration with the Fraunhofer Institute for Cell Therapy and Immunology (IZI) and acquired related patents from the Institute for a meprin protease inhibitor and assay platform. Under the guidance of PD Dr. Stephan Schilling, the Department of Drug Design and Target Validation will work together with Vivoryon to advance first-in-class small molecule meprin inhibitors. This collaboration will combine Vivoryons expertise in translating basic research into marketable small molecule therapeutics with the departments focus on discovery and development of new therapeutics that target putative pathologic post-translational modifications.

The metal-dependent proteases, meprin alpha and meprin beta, are emerging targets in kidney protection, fibrotic diseases, cancer and Alzheimers disease. Increased meprin expression and their mislocalization has been associated with tissue damage and collagen deposition in fibrosis, which can result in the loss of organ function. Meprin-targeted protease inhibitors thus have the potential to not only target symptoms, but also treat a range of indications including acute and chronic kidney disease and multiple organ fibrosis.

Dr. Michael Schaeffer, CBO at Vivoryon Therapeutics AG noted:The IP estate we have acquired from Fraunhofer IZI expands our current drug development portfolio and places us in a leading position to explore the full potential of meprin protease inhibitors. As a company, our goal is to consistently seek out opportunities that can further strengthen our pipeline with the ultimate vision of delivering novel therapies to patients in need. By working with Dr. Schilling and his team we are set to advance meprin inhibitors very quickly towards clinical testing in indications like fibrotic diseases or cancer.

PD Dr. Stephan Schilling, Head of Protein and Drug Biochemistry Unit at Fraunhofer Institute for

Cell Therapy and Immunology added:As the roles and functionality of meprin alpha and beta continue to become more distinguished through research, it is clear these metalloproteases represent interesting novel targets that could be developed into therapeutics for a variety of indications. As such, I am delighted that with this collaboration the groundbreaking research of our institute will eventually be translated into clinical programs by an experienced drug development company.

###

For more information, please contact:

Vivoryon Therapeutics AG

Dr. Ulrich Dauer, CEO

Email:contact@vivoryon.com

Fraunhofer Institute for Cell Therapy and Immunology

Jens Augustin, Head of Press and Public Affairs

E-Mail:presse@izi.fraunhofer.de

Trophic Communications

Gretchen Schweitzer / Joanne Tudorica

Tel: +49 172 861 8540 / +49 176 2103 7191

Email:Trophic@vivoryon.com

About Vivoryon Therapeutics AG

With 20+ years of unmatched understanding in identifying post-translational modifying enzymes that play critical roles in disease initiation and progression, Vivoryons scientific expertise has facilitated the creation of a discovery and development engine for small molecule therapeutics. This platform has demonstrated success by developing a novel therapeutic in type 2 diabetes. In its current programs Vivoryon Therapeutics is advancing its lead product, PQ912, in Alzheimers disease and its entire portfolio of QPCT and QPCTL inhibitors in oncology and other indications.

http://www.vivoryon.com

About Fraunhofer-Gesellschaft

The Fraunhofer-Gesellschaft, headquartered in Germany, is the worlds leading applied research organization. With its focus on developing key technologies that are vital for the future and enabling the commercial exploitation of this work by business and industry, Fraunhofer plays a central role in the innovation process. As a pioneer and catalyst for groundbreaking developments and scientific excellence, Fraunhofer helps shape society now and in the future. Founded in 1949, the FraunhoferGesellschaft currently operates 74 institutes and research institutions throughout Germany. The majority of the organizations 28,000 employees are qualified scientists and engineers, who work

with an annual research budget of 2.8 billion euros. Of this sum, 2.3 billion euros is generated through

contract research.

http://www.izi.fraunhofer.de

Forward Looking Statements

Information set forth in this press release contains forward-looking statements, which involve a number of risks and uncertainties. The forward-looking statements contained herein represent the judgment of Vivoryon Therapeutics AG as of the date of this press release. Such forward-looking statements are neither promises nor guarantees but are subject to a variety of risks and uncertainties, many of which are beyond our control, and which could cause actual results to differ materially from those contemplated in these forward-looking statements. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any such statements to reflect any change in our expectations or any change in events, conditions or circumstances on which any such statement is based.

See the original post here:
Vivoryon Therapeutics Starts Development Program for Meprin Protease Inhibitors with Intended Therapeutic Use in Fibrosis, Cancer and Alzheimer's...

Immunology

Could genetics explain why some COVID-19 patients fare worse than others? – Live Science

Certain genetic differences might separate people who fall severely ill with COVID-19 from those who contract the infection but hardly develop a cough, a new preliminary study suggests.

The research is still in its early days, though, experts say.

The immune system can react to viruses thanks, in part, to specific genes that help cells spot unfamiliar bugs when they enter the body. The genes, known as human leukocyte antigen (HLA) genes, contain instructions to build proteins that bind to bits of a pathogen; those proteins serve as warning flags to alert immune cells. The immune cells, once trained to recognize these bits, jumpstart the process of building antibodies to target and destroy the invasive germ.

Within each individual, HLA genes code for three different classes of proteins; in other words, HLAs come in a variety of flavors, and depending on which HLAs you have, your body may be better or worse equipped to fight off certain germs including SARS-CoV-2, the virus that causes COVID-19.

In a new study, published April 17 in the Journal of Virology, researchers used computer models to predict which combination of HLAs might be best at binding SARS-CoV-2, and which might be worst.

If certain HLAs can bind well to a large proportion of the virus's proteins, "we expect there to be a more protective immune response," authors Abhinav Nellore and Dr. Reid Thompson, who lead a computational biology research group at the Oregon Health and Science University, told Live Science in an email. A better bind means that the viral proteins are more likely to be presented to immune cells and prompt the production of specific antibodies, the authors said.

"If the interaction is not stable, you will not have a proper [immune] response," said Dr. Shokrollah Elahi, an associate professor in the Department of Dentistry and adjunct associate professor in the Department of Medical Microbiology and Immunology at the University of Alberta, who was not involved in the study.

Related: 10 deadly diseases that hopped across species

But a stable bond, alone, does not guarantee the best immune response, Elahi added. If an HLA binds a viral protein that happens to be critical for the germ to replicate and survive, the subsequent antibody activity will likely target the virus more effectively than that prompted by a less important protein, Elahi said.

"This is an issue we did not address in our analysis," the authors noted. Instead, the team focused on predicting how well different HLA types could bind to bits of SARS-CoV-2. Their analysis identified six HLA types with a high capacity to bind different SARS-CoV-2 protein sequences, and three with a low capacity to do so. Specifically, a HLA type known as HLA-B*46:01 had the lowest predicted capacity to bind to bits of SARS-CoV-2.

The same HLA type cropped up in a 2003 study published in the journal BMC Medical Genetics, which assessed patients infected with SARS-CoV, a closely related coronavirus that caused an outbreak of severe acute respiratory syndrome in the early 2000s. The study found that, in a group of patients of Asian descent, the presence of HLA-B*46:01 was associated with severe cases of the infection. In their paper, the research group noted that more clinical data would be needed to confirm the connection and the same goes for the new study of SARS-CoV-2, Nellore and Thompson said.

"The most substantial limitation of our study is that this was conducted entirely on a computer and did not involve clinical data from COVID-19 patients," the authors said. "Unless and until the findings we present here are clinically validated, they should not be employed for any clinical purposes," they added.

"In the body, we have so many things interacting," Elahi said. HLAs represent just one piece of a large, intricate puzzle that comprises the human immune system, he said. To better understand the variety of immune responses to COVID-19, Elahi and his research group aim to assess markers of immune system activity in infected patients and also catalog the ratio of immune cell types present in their bodies. While taking age, sex and other demographic factors into account, these so-called immunological profiles could help pinpoint when and why the illness takes a turn in some patients.

The clinical data could be assessed in parallel with genetic data gathered from the same patients, Elahi added. Similarly, Nellore and Thompson said that "COVID-19 testing should be paired with HLA typing, wherever [and] whenever possible," to help determine how different HLA types relate to symptom severity, if at all. Partnerships with genetic testing companies, biobanks and organ transplant registries could also offer opportunities to study HLA types in larger populations of people, they said.

"We cannot in good conscience predict at this point who will be more or less susceptible to the virus because we have not analyzed any clinical outcomes data with respect to HLA type to know that any of our predictions are valid," the authors said. If future studies support the notion that some HLA genes protect people from the virus, while others place patients at greater risk, those in the latter group could be first in line for vaccination, they added.

"In addition to prioritizing vaccinating the elderly or those with preexisting conditions, one could prioritize vaccinating people with HLA genotypes that suggest the SARS-CoV-2 virus is more likely to give them worse symptoms."

The authors went on to analyze how well HLAs can bind SARS-CoV-2 as compared with other coronaviruses, such as those that cause the common cold and infect humans often. They identified several viral bits shared between SARS-CoV-2 and at least one of these common viruses, suggesting exposure to one germ could somewhat protect the body against the other.

"If someone was previously exposed to a more common coronavirus and had the right HLA types ... then it is theoretically possible that they could also generate an earlier immune response against the novel SARS-CoV-2," the authors said. On the other hand, exposure to a similar virus could leave the body ill-equipped to fight off the new one, if, for instance, "the body is using an old set of tools that aren't ideally suited to address the new problem," the authors said.

Originally published on Live Science.

See the rest here:
Could genetics explain why some COVID-19 patients fare worse than others? - Live Science

Immunology

Outlook 2020: ‘Passionate about helping to train the next generation of physicians, scientists,’ Judith James says – Oklahoman.com

Name: Dr. Judith James, 52.

Career highlights: Oklahoma Medical Research Foundation vice president of Clinical Affairs; member and program chair, Arthritis & Clinical Immunology Research Program; Lou C. Kerr Endowed Chair in Biomedical Research; associate vice provost for Clinical and Translational Science; George Lynn Cross Professor of Research, professor of medicine, professor of pathology, adjunct professor of microbiology and immunology, Oklahoma University Health Sciences Center.

Community impact: As a leader in the Oklahoma Shared Clinical Translational Resources, James helps oversee partnerships between 29 entities within the state whose mission is to improve health and health outcomes. Along with universities, the program includes tribal health services.

James also works with the Cherokee Nation and the Chickasaw Nation at outreach clinics to improve tribal members with rheumatic diseases.

Life philosophy and advice to young women: "I am incredibly passionate about helping to train the next generation of physician and physician scientists," James said. "When I started in medical school, less than 30% of my class was female. And now we're close to 50%. And so I hope that I will encourage, inspire, motivate and facilitate their ability to think about how they can help improve the health and research training, for everyone. But especially for women."

Dale Denwalt, Staff writer

Visit link:
Outlook 2020: 'Passionate about helping to train the next generation of physicians, scientists,' Judith James says - Oklahoman.com

Immunology

New research gives further evidence that autoimmunity plays a role in Parkinsons disease – Newswise

Newswise LA JOLLAA new study co-led by scientists at the La Jolla Institute for Immunology (LJI) adds increasing evidence that Parkinsons disease is partly an autoimmune disease. In fact, the researchers report that signs of autoimmunity can appear in Parkinsons disease patients years before their official diagnosis.

The research could make it possible to someday detect Parkinsons disease before the onset of debilitating motor symptomsand potentially intervene with therapies to slow the disease progression.

The study, published in the April 20, 2020, issue of Nature Communications, was co-led by LJI professor Alessandro Sette, Dr. Biol. Sci, and Professor David Sulzer, Ph.D., of the Columbia University Medical Center.

Scientists have long known that clumps of a damaged protein called alpha-synuclein build up in the dopamine-producing brain cells of patients with Parkinsons disease. These clumps eventually lead to cell death, causing motor symptoms and cognitive decline.

Once these cells are gone, theyre gone. So if you are able to diagnose the disease as early as possible, it could make a huge difference, says LJI research assistant professor Cecilia Lindestam Arlehamn, Ph.D., who served as first author of the new study.

A 2017 study led by Sette and Sulzer was the first to show that alpha-synuclein can act as a beacon for certain T cells, causing them to mistakenly attack brain cells and potentially contribute to the progression of Parkinsons. This was the first direct evidence that autoimmunity could play a role in Parkinsons disease.

The new findings shed light on the timeline of T cell reactivity and disease progression. The researchers looked at blood samples from a large group of Parkinsons disease patients and compared their T cells to a healthy, age-matched control group. They found that the T cells that react to alpha-synuclein are most abundant when patients are first diagnosed with the disease. These T cells tend to disappear as the disease progresses, and few patients still have them ten years after diagnosis.

The researchers also did an in-depth analysis of one Parkinsons disease patient who happened to have blood samples preserved going back long before his diagnosis. This case study showed that the patient had a strong T cell response to alpha-synuclein ten years before he was diagnosed with Parkinsons disease. Again, these T cells faded away in the years following diagnosis.

This tells us that detection of T cell responses could help in the diagnosis of people at risk or in early stages of disease development, when many of the symptoms have not been detected yet, says Sette. Importantly, we could dream of a scenario where early interference with T cell responses could prevent the disease from manifesting itself or progressing.

Sulzer added, One of the most important findings is that the flavor of the T cells changes during the course of the disease, starting with more aggressive cells, moving to less aggressive cells that may inhibit the immune response, and after about 10 years, disappearing altogether. It is almost as if immune responses in Parkinsons disease are like those that occur during seasonal flu, except that the changes take place over ten years instead of a week.

In fact, already therapies exist to treat inflammation from autoreactive T cells, and these TNF therapies are associated with lower incidence of Parkinsons disease. Going forward, the researchers are especially interested in using a tool called a T cell-based assay to monitor patients already at risk for Parkinsons to see if they could benefit from TNF therapies. These patients include people with REM sleep disorders and certain genetic mutations.

The researchers hope to study more Parkinsons patients and follow them over longer time periods to better understand how T cell reactivity changes as the disease progresses.

The study, titled -Synuclein-specific T cell reactivity is associated with preclinical and early Parkinsons disease, was supported by the National Institutes of Healths (NIH) National Institute of Neurological Disorders and Stroke (R01NS095435, P50NS108675), the NIH National Institute on Aging (P50AG08702), the Parkinsons Foundation, the Michael J. Fox Foundation, JPB Foundation, William F. Richter Foundations, and the UCSD-LJI Program in Immunology.

Additional study authors included Rekha Dhanwani, John Pham, Rebecca Kuan, April Frazier, Juliana Rezende Dutra, Elizabeth Phillips, Simon Mallal, Mario Roederer, Karen S. Marder, Amy W. Amara, David G. Standaert, Jennifer G. Goldman, Irene Litvan, and Bjoern Peters.

DOI: 10.1038/s41467-020-15626-w

About La Jolla Institute for Immunology

The La Jolla Institute for Immunology is dedicated to understanding the intricacies and power of the immune system so that we may apply that knowledge to promote human health and prevent a wide range of diseases. Since its founding in 1988 as an independent, nonprofit research organization, the Institute has made numerous advances leading toward its goal: life without disease.

###

Read the original:
New research gives further evidence that autoimmunity plays a role in Parkinsons disease - Newswise

Anatomy

Bolton 1-3 Reading FC: The Anatomy Of A Perfect Away Day – The Tilehurst End

Its an age-old conversation topic for football fans that can easily fill an evening in the pub, or multiple for the die-hard. Whats your favourite ever away game?

Reading fans are pretty blessed in this regard. The obvious answers include Southampton and West Ham away in 2012, the play-off demolition of Cardiff a year earlier, and the Bryniesta inspired beating Liverpool in the FA Cup.

But every fan has their personal favourites, those perfect days that rest in the lower tiers of Reading folklore. Mine include the 3-1 promotion six-pointer win at Birmingham in 2008, the 1-1 draw at Old Trafford earned by our second-string XI in the 2006/07 FA Cup. And then theres Bolton.

On April 21, 2007, 13 years ago as I sit here today, Steve Coppells side found themselves 1-0 down to Bolton at the Reebok Stadium with 83 minutes on the clock. On the face of it, this isnt a particularly impressive prologue to a Lazarus-esque tale.

But Reading were dreaming of Europe in their first season of Premier League football, and Sam Allardyces side were a major rival with established faces such as Nicolas Anelka, Kevin Nolan and El Hadji-Diouf in their ranks. It was also a chance to see how the other half lives. A decade-and-a-half earlier, Bolton were not an intrinsically bigger team and their rise in that period set the blueprint for the Royals own ambitions - having featured something of a fork in the road 12 years earlier.

The hosts had generally been the better team for those 83 minutes. Anelkas second-half opener came via an unfortunate attempted block from Nicky Shorey but couldnt really be argued with. Readings best chance came in an agonising goalmouth scramble that suggested a typically tough day in the life of a small fish in a big pond.

Then the last six minutes happened. Kevin Doyles frankly rude insistence on running at goal brought an errant leg from Abdoulaye Meite. That was the thing about that Reading team, they didnt care who you played for, they just turned up and beat you. They didnt know they were born. The Irishman picked himself up to slot home the equaliser.

Bolton keeper Jussi Jaaskelainen prepared to take a goal kick a minute later and took his time, earning a hounding from his own supporters desperate to re-take the lead. If only they knew what he knew. In the 89th minute, a cross from the right floated over to Doyle whose brazen arrogance allowed time for the ball to settle perfectly on the six-yard line, Bolton studs stabbing at his heels, before belting it home.

Reading had the lead but the fun wasnt over. Shorey tricked his way down the left wing and a perfect cross was only inches over the head of a hat-trick hunting Doyle. That left Shane Long with a free header to make it 3-1. Little did he know Stephen Hunt was barrelling in at 100mph, blinkers on, to headbutt the ball into the back of the net.

The atmosphere in the away end was next level. Its best shown by the photo at the top of this article as Doyle celebrates the equaliser, I can see 13-year-old me and my dad celebrating, split by the fan in the row above whose somehow been lifted six feet in the air. The final whistle rang around a suddenly empty Reebok Stadium - sending the home fans back down the stairs early being one of the finest and most unique joys of following football on the road.

There was still one Bolton fan looking on in disbelief, as the boxer Amir Khan stood in his executive box near the away end, and received hundreds of playful taunts by joyous visitors singing of a dream European Tour. It was also our first win on their turf since a certain day in 1995, a memory no doubt resonating in the minds of many that day.

For myself, 2006/07 was my first season on the road with Reading and Im sure Ive never beaten the W3 D1 L1 record I witnessed that campaign. With our family connections up north, my mum had come up with us and visited the retail park next door during the game. All that loud cheering, she was worried we had received a battering... until we told her it was the away end going bananas.

It is also timely that the anniversary of that beautiful Lancastrian day lands on an equally lovely day in our very different world. On these football-less times, memories like these remind us why we all cant wait to do it all again.

Read this article:
Bolton 1-3 Reading FC: The Anatomy Of A Perfect Away Day - The Tilehurst End