Category Archives: Immunology

Board of Trustees to be created at RSPC for pediatric oncology, hematology and immunology – TVR

The Board of Trustees will monitor the development of the center: it will coordinate the work of the business and the healthcare system and will inform the population. Natalia Kochanova expressed her wish for all the senators to be involved. The chairwoman of the Upper House visited young patients and held a round table discussion on the implementation of the pilot project, housing construction for employees, improving the working conditions of young specialists with the representatives of the Ministry of Health.

Vladimir Karanik, Minister of Health of Belarus: "We are in the top twenty countries in the cure rate of the children in the world. In general, 75% of childrens oncology diseases are cured. This figure has not reached 100 percent, but we will continue to work to improve the results."

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Board of Trustees to be created at RSPC for pediatric oncology, hematology and immunology - TVR

Probiotics: Don’t Buy the Online Hype – HealthDay

WEDNESDAY, Jan. 15, 2020 (HealthDay News) -- Many people turn to the internet with health questions, but how reliable is the information you find? When it comes to probiotics, a new study urges caution.

The research found that of 150 websites that came up with a search of probiotics, most were commercial sites, hoping to sell a product. Others were news sites or health portals (providing links to other sites). Many of these sites mentioned potential benefits of probiotics, though not all had scientific evidence to back up those claims. And just 1 in 4 of the websites mentioned any potential side effects from taking probiotics.

"This study demonstrates that a number of online claims on the health benefits of probiotics are not supported by scientific evidence," said study co-author Dr. Michel Goldman, a professor of immunology at the Universite Libre de Bruxelles in Belgium.

Probiotics are "good" bacteria found in yogurt and other fermented foods and in dietary supplements, according to the U.S. National Center for Complementary and Integrative Health. Some of these bacteria are also found naturally in the human body. They may help digest food, fight germs that can cause disease, or produce vitamins.

"Probiotics can clearly be helpful in the management of infectious diarrhea, in pregnant women with gestational diabetes, and as an adjunct to food allergy desensitization therapy," Goldman said. He added that probiotics might also be helpful for the skin condition eczema and for some urinary or genital infections in women.

But his team saw some broad claims online about probiotics' benefits, such as being beneficial in treating cancer. There's no scientific evidence to support those claims.

For the study, Goldman and his colleagues looked at the first 150 pages brought up by Google in response to a search for "probiotics." They reviewed the information on these pages for reliability and searched a large database of clinical trials for evidence supporting those claims.

One bright spot was that Google appears to prioritize more reliable sources of information over commercial websites.

Still, consumers should be wary of health information they get online.

"Consumers should look whether there is scientific information published in peer-reviewed medical journals supporting claims to probiotics and over-the-counter health products that are not regulated as rigorously as prescription drugs. They should discuss with their doctors, the benefits they can expect from probiotics," Goldman said.

Dr. Melinda Ring, executive director of the Osher Center for Integrative Medicine at Northwestern University in Chicago, said she wasn't surprised by the findings.

"This is a big problem in the natural product and dietary supplement area. There's a preponderance of less reputable information from sales and commercial sources," said Ring, who wasn't part of the research.

"People really need to look at the claims websites are making. Are they promising unrealistic cures? Are they referencing scientific data?" she said.

One area where probiotics may be helpful is in maintaining the body's natural balance of beneficial bacteria -- the gut microbiome. "We know the human microbiome is incredibly important to our health and the development of disease, but we're just in the infancy of understanding how to manipulate the microbiome," Ring said.

If you're interested in improving your gut's microbiome, the first place to start is improving your diet, because what you eat is also food for your microbiome, Ring said. Focus on vegetables, fruits and whole grains.

A number of foods have probiotics, such as yogurt and fermented foods. But sometimes the probiotics that occur naturally in foods can be destroyed by processing and preserving. Ring recommended looking for "live cultures" on the packaging.

If you take probiotic supplements, she suggested sticking with reputable brands, and perhaps taking more than one product to make sure you're getting a diversity of probiotics.

Andrea Wong is senior vice president of scientific and regulatory affairs for the Council for Responsible Nutrition (CRN), which represents the supplement industry. She said that research demonstrates that probiotics are safe and have health benefits.

"When it comes to reliable information on probiotics and other dietary supplements, doctors and other health care practitioners are the most trusted sources. CRN encourages consumers to be smart shoppers and do their due diligence when looking for dietary supplement information," Wong said.

The findings were published Jan. 15 in Frontiers in Medicine.

More information

Learn more about probiotics from the U.S. National Center for Complementary and Integrative Health.

SOURCES: Michel Goldman, M.D., Ph.D., professor, immunology, Universite Libre de Bruxelles, and co-director, 13th Institute, Belgium; Melinda Ring, M.D., executive director, Osher Center for Integrative Medicine, Northwestern University, Chicago; Andrea Wong, Ph.D., senior vice president, scientific and regulatory affairs, Council for Responsible Nutrition; Jan. 15, 2020, Frontiers in Medicine

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Probiotics: Don't Buy the Online Hype - HealthDay

Lucid Group expands its presence in the north-west with six new hires – PMLiVE

Healthcare 21, a Lucid Group company, continues to strengthen its editorial and medical writing team with six new additions to its Macclesfield office.

Rosanna Farrell joins HealthCare 21 as a Senior Editorial Assistant. Rosanna has 7 years experience in editorial, working with TimeOut London, The Big Issue and The London 2012 Olympics programmes.

Becca Winkle joins HealthCare 21 as an Editorial Assistant. Becca has an MA in English Literary Studies, English Literature and Literary Theory as well as previous teaching and editorial experience. Becca comments I became interested in MedComms because, as someone with a passion for English Language and Literature, I recognise the importance of the style and functionality of language when conveying information about complex subjects or issues. As an Editorial Assistant at HealthCare21, Im excited to be part of a process that ultimately leads to a better experience for healthcare professionals and patients receiving care.

Alex Nicholson joins HealthCare 21 as an Editorial Assistant. Alex has a degree in English and French and a PGCE in Modern Languages and he is currently studying for his StEP Proofreading 2: Headway. Alex previously worked as a freelance transcriber for a document service company and runs a blog on popular culture, sport and current affairs.

Nicole Scullion joins HealthCare 21 as a Trainee Medical Writer. Nicole has an MRes in Biomedical Sciences and Translation Medicine from the University of Liverpool where she focussed on cancer biology and the response of uveal melanoma.

Sophie Day also joins HealthCare 21 as a Trainee Medical Writer. Sophie has a BSc in Biology from the University of Manchester where she completed her dissertation in Science Media and Communication.

Areeba Ali joins HC21 as a trainee medical writer. Originally from Ireland she moved to Manchester to pursue a Masters in Clinical Immunology. Areeba comments, Im very excited to be joining such a people-centric organisation with such a focus on transforming patients lives.

If you are interested in being part of something magical, get in touch.

Contact Dan Newbury, Talent Acquisition ManagerEmail: Daniel@lucid-group.co.ukTel: 01494 755495

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Lucid Group expands its presence in the north-west with six new hires - PMLiVE

CIMZIA approved for use by Health Canada – Spinal News International

Syringe with Certolizumab pegol

UCB Canada has announced that CIMZIA (certolizumab pegol) for the treatment of adults with severe active non-radiographic axial spondyloarthritis (nr-axSpA), has been approved for use by Health Canada.

The treatment is targeted at adults with objective signs of inflammation as indicated by elevated C-reactive protein (CRP) and/or magnetic resonance imaging (MRI) evidence who have had an inadequate response to, or are intolerant to nonsteroidal anti-inflammatory drugs (NSAIDs).

Health Canadas approval is based on data from C-AXSPAND5, a Phase 3, multicentre, double-blind, placebo-controlled 52-week study that randomised 317 adult patients to receive either CIMZIA or placebo plus common background medications, which included NSAIDs, corticosteroids, analgesics and slow-acting anti-rheumatic drugs. The study met its primary endpoint, with 47.2% of patients treated with CIMZIA demonstrating major improvement response in Ankylosing Spondylitis Disease Activity Score (ASDAS-MI) at week 52, compared to 7.0% of patients treated with placebo. Detailed findings from the study were published online in Arthritis & Rheumatology in March 2019.

Were pleased to see this important advance for the spondyloarthritis community. Greater awareness, earlier diagnosis and more treatment options will help deliver better outcomes for Canadians living with this painful disease which often falls through the cracks, and carries with it a significant burden, said Gerald Major, president, Canadian Spondylitis Association.

The approval marks the fifth indication for CIMZIA, which is the only Fc-free, PEGylated anti-TNF option available for the treatment of the disease where significant unmet need currently exists, UCB said in a press release.

The journey patients face from symptom onset to diagnosis and receiving appropriate treatment can be extremely lengthysometimes up to 10 years. So having a new and effective option for nr-axSpA is welcome news, both for those suffering and their physicians who are seeking a proven treatment to reduce the severe pain, stiffness, and other burdensome symptoms of the disease, said Walter Maksymowych, professor and medical scientist in the Department of Medicine, Division of Rheumatology at the University of Alberta (Edmonton, Canada).

The approval of CIMZIA for nr-axSpA is an important treatment advance which builds on more than a decade of market experience and proven efficacy and safety, said Lionel Houle, head of immunology, UCB Canada.

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CIMZIA approved for use by Health Canada - Spinal News International

JPM, Day 3: AbbVie duo’s $20B ambitions, GSK and Pfizer’s what-next moment and Amarin’s clear runway – FiercePharma

We're not gonna lieWednesdays at the J.P. Morgan Healthcare Conference feel a bit anticlimactic. Two days of meetings, presentations, panels and cocktail hours are past, and we can see the end in sight.

But that doesn't mean the action has come to a halt. Indeed, we picked up some unprecedented talk from AbbVie CEO Rick Gonzalez first thing Wednesday morning, and by day's end had heard some even bigger numbers from a GlaxoSmithKline vaccines exec.

Now, our JPM on-site team is dispersing, recapping and digging through notebooks for quotes that captured the whirlwind conference-in-progress. Here's what we heardand what we're thinkingafter Day 3.

Artificial Intelligence in the Pharma Industry

How far has the adoption of AI technology come in Life Sciences? Share your thoughts in this brief, 8-minute survey. Let your voice be heard.

Missed our previous roundups? Here areDay 1 and Day 2. And check out our collectedJPM coverage: FierceBiotech's here and FiercePharma's here.

GlaxoSmithKline and Pfizer seem to have contradictory visions for their consumer health joint venture. During a Tuesday presentation, Pfizer chief Albert Bourla said he believes the JV is heading toward an IPO within three to four years in a move that provides the New York pharma a clear exit strategy. Maybe not, GSKs chief strategy officer David Redfern saidin an interview with Bloomberg the following day. "And its entirely our decision, Redfern said. Story

At Wednesdays first presentation, AbbVie CEO Richard Gonzalez talked up the potential of two thedrugmakersnew immunology launchesSkyriziandRinvoq. While only approved in psoriasis and rheumatoid arthritis right now, respectively, Gonzalez said he expects the meds to pick up newindications toeventually match or best Humira, AbbVies almost-$20 billionmegablockbuster. If pricing holds steady, he could envision the meds reaching $20 billion in sales or more, easily picking up where Humira leaves off as biosimilars enter the U.S.in 2023. Story

GSKsShingrixgenerated blockbuster sales quickly after its launch, but numberstouted by thedrugmakerthis weekshow the size of the remaining opportunityand how much supply constraints have held the rollout back.The company figures a massive 115 million people in the U.S. alone would be eligible for Shingrix,GSKs vaccines presidentRoger Connor toldFiercePharma at JPM. The company'slooking everywhere to increase capacity, but its started to hit a bottleneck," with true relief several years away. Story

Amarin's been revving up for Vascepa's big CVlaunch in the U.S., and now thatAstraZenecas Epanova flopped a major trial, its field is clear of competitors. In Europe, Vascepa is still awaiting its regulatory review for CV risk reduction, but that hasn't stoppedother drugmakers from sniffing around for possible licensing opportunities, CEO John Thero told investors Wednesday. Not interested, Thero saidat least not yet. Amarin sees more value in waiting out the regulatory process before considering a deal. Its still a bit premature to get too far along in these conversations as we think the value will increase as the regulatory process proceeds in Europe, he said. Story

MichaelGoettler, CEO-to-be of the newViatris, said the combination of Mylan and Upjohn will have global scale and geographic reach, and will be a partner of choice for midsizeddrugmakersseeking to reach new markets. The combination makes sense because together the companies will have a sustainable and diverse portfolio,plusstrong commercial capabilities and financialperformance,Goettlersaid.

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JPM, Day 3: AbbVie duo's $20B ambitions, GSK and Pfizer's what-next moment and Amarin's clear runway - FiercePharma

JPM: How will Amgen make its $13.4B Otezla buy pay off? New launches, for one, CEO says – FiercePharma

SAN FRANCISCOWhen Amgen shelled out $13.4 billion late last year to pick up Celgene's blockbuster immunology med Otezla, it made a calculated guess the drug had some untapped fuel in its commercial tank. Now, Amgen is looking to rev up sales with new indications and launches in new international markets.

Although scant on details, Amgen CEO Bob Bradway forecast Tuesdaythat Amgen could squeeze more out of Otezla in the coming yearsafter the drug hit $547 million in sales in the third quarterassuming Amgen can follow its own mantra and execute.

"In biopharma, the focus is on innovation, innovation, innovation, and Amgen is execution, execution, execution," Bradway told investors at the annual J.P. Morgan Healthcare Conference in San Francisco.

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In Bradway's telling, Otezla helped Amgen flesh out its immunology portfolio as a counterpart to stalwart Enbrel.

"We think the stars really aligned for us in 2019 when we were able to acquire Otezla," Bradway said. "Otezla is a great medicine, it has great valuefor us, and it came at a great time."

RELATED:Amgen, maker of Enbrel, to pick up Celgene's Otezla for $13.4B. Will FTC hit back?

Amgen picked up Otezla in a$13.4 billion deal with Celgene in August as the latter worked to secure its$74 billion merger with Bristol-Myers Squibb.

Bristol was forced to sell Otezla to win the Federal Trade Commission's clearance simply because it overlappedwith BMS own investigational TYK-2 inhibitor, BMS-986165. Despite Amgen's blockbuster Enbrel operating in the same market, the deal passed muster.

At the time, Amgen expected Otezla could enjoy at least low double-digit sales growth on average over the next five years. The Streets consensus currently has it reaching $2.5 billion in peak sales before presumably going off patent in the U.S. in 2028. At that rate,Amgen will at least be able to get its investment back in full by around 2024.

Looking ahead, Amgen expects phase 3 data for Otezla in mild to moderate psoriasis will read out this year, and the drugmaker hopes to launch the drug beyond the30-oddinternational markets where it's currently approved, Bradway said.

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JPM: How will Amgen make its $13.4B Otezla buy pay off? New launches, for one, CEO says - FiercePharma

Why There’s No Such Thing as a Truly Hypoallergenic Dog – Healthline

If you become congested and start to sneeze anytime youre near a dog, youre not alone. The American College of Allergy, Asthma, and Immunology (ACAAI) reports that almost 10 million people are allergic to their pets.

For many pet owners, buying a hypoallergenic dog sounds like the perfect solution. No more allergy pills or shots and you can still have a cute, furry friend. It sounds perfect, right?

However, when Healthline asked several allergy experts about hypoallergenic dogs, they all gave us a very emphatic no.

Theres no such thing as a truly hypoallergenic dog.

However, there are many options to consider that may allow you to own a dog without triggering a reaction if youre a person living with pet allergies.

According to allergist Dr. Tania Elliott, a spokesperson for the ACAAI, people can develop allergic reactions to pet dander (similar to dandruff in humans), saliva, urine, and hair.

When exposed to these substances, our body can mistakenly see certain proteins within them, called allergens, as a threat. To protect us, our body develops antibodies against those proteins.

When were exposed to those proteins again, we then have an allergic response. Our immune system will be activated, causing the release of histamine.

Histamine causes symptoms, such as sneezing and increased mucus production, which protect us from the invading protein.

These symptoms are what cause the discomfort we associate with an allergy.

In the case of a dog allergy, Elliott says you could develop symptoms such as itchy eyes, runny nose, asthma attacks, sneezing, and/or congestion.

You might also develop hives if youve been touched or licked by a dog.

According to Dr. Jill A. Poole, professor, division chief of allergy and immunology at the department of medicine at the University of Nebraska Medical Center, theres no such thing as a hypoallergenic dog because all dogs produce the same proteins.

Its those proteins to which youre reacting. Thats why even a so-called hypoallergenic dog can still trigger an allergic reaction.

It would be more appropriate, Poole said, to call these shedding versus non-shedding dogs.

Shedding dogs release more dog hair into their environment, leading to a buildup of dog hair in your home.

Non-shedding dogs tend to not shed their hair as easily. They must be regularly groomed to prevent matting.

When dogs shed, some people can develop an irritant response to the hair.

While the symptoms can be the same, an irritant response is different from an allergic response. Irritation doesnt trigger the production of antibodies the way an allergy does.

If you experience an irritant response to dog hair, having a dog that sheds less would reduce this.

Being vigilant about keeping loose dog hair cleaned up would also help those who are experiencing an irritant response, says Poole.

Poole says your first step in getting tested for a dog allergy would be to talk with a doctor or allergist about your symptoms and medical history. If these indicate a possible dog allergy, they can order a test for you.

This testing would be either a skin test or a blood test.

Skin and blood tests are similar in that they can detect the antibodies in your skin and blood that trigger an immune response to a particular allergen.

In a skin test, a small amount of a diluted allergen is placed under your skin, either by pricking the skin or by injection.

If you develop a red, itchy bump, called a wheal, within about 15 minutes, youre considered to be allergic to that particular allergen.

A blood test would involve drawing blood and testing it in a laboratory for the presence of antibodies.

While theres no such thing as a hypoallergenic dog, it appears that some people with dog allergies may not be allergic to all dogs.

Theres recent research indicating that people who are allergic to a specific dog protein called Can f 5 might only react to intact male dogs.

Poole explains this means that some people with dog allergies could potentially own either a female or a neutered male dog and wouldnt have an allergic reaction.

There are six different proteins that have been been identified as causing allergies in dogs: Can f 1 to 6.

Can f 5 is only produced in the prostate gland of the male.

Because of this fact, a female dog wouldnt produce an allergic reaction in people who are allergic to only this one allergen.

A neutered male produces less of this protein and might also be a safe choice.

About 30 percent of people with dog allergies are allergic to only the Can f 5 protein, Poole says.

Dr. Princess Ogbogu, director of allergy and immunology at Ohio State University Wexner Medical Center, does caution that its a bit premature to make this a standard clinical recommendation.

It is a hypothesis and not well established yet, Ogbogu said.

However, if youd like to explore this avenue further, you can speak with your doctor about testing.

A test for allergy to the Can f proteins was approved by the Food and Drug Administration in May 2019.

Poole says its important that youre tested for all of the Can f allergens and not just Can f 5. You could be allergic to more than one of them.

If youre not one of the lucky few who are only allergic to Can f 5, there are several other steps you can take that may allow you to have a canine in your home.

Poole suggests the first place to start is to try limiting your exposure to the offending allergens through environmental controls.

According to the ACAAI, environmental controls could include such things as:

Another step you can take is to use medications to manage your allergy symptoms.

Your allergist can recommend which medications will be best for you, depending on your individual symptoms.

Medications your doctor might prescribe include:

Finally, although it can be time-consuming, immunotherapy does offer more of a permanent solution to dog allergies.

Poole explains it takes about 3 to 5 years to desensitize a person to an allergen.

The protocol involves giving the person a gradually increasing dose of the allergen once or twice a week until they reach a maintenance dose.

At this point, theyd then need an injection every 2 to 4 weeks over the course of about 3 to 5 years.

Each injection is given subcutaneously (in the fat layer between the skin and muscle).

The person is then observed by a medical professional for 30 minutes in case they have an adverse reaction to the allergen.

Immunotherapy can greatly reduce, or even completely eliminate, your allergy symptoms.

Many people who love dogs are unfortunately allergic to them.

While a hypoallergenic dog might seem like a good solution, allergy experts say theres really no such thing as a hypoallergenic dog.

However, this doesnt mean youre without options. There are ways to reduce or eliminate your exposure to dog allergens. You can also take medications that manage your symptoms or have immunotherapy to desensitize you to dog allergens.

An allergist can help you learn more about your options.

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Why There's No Such Thing as a Truly Hypoallergenic Dog - Healthline

Gilead Backs Startup Kyverna Therapeutics with Financing, Collaborative Agreement – BioSpace

Gilead Sciencesis boosting support for a Bay Area startup looking to develop a new class of therapies for autoimmune diseases. Gilead, along with two venture capital groups, provided Kyverna Therapeutics with an infusion of $25 million and also struck a collaboration with the fledgling company.

On Monday, Kyverna announced it had closed a $25 million Series A investment from Gilead, Vida Ventures and Westlake Village BioPartners, which will be used to advance the companys platform that combines advanced T cell engineering and synthetic biology technologies to suppress and eliminate autoreactive immune cells at the root cause of inflammatory disease. In addition to the cash, Gilead and Kyverna entered into a collaboration and license agreement to develop engineered T cell therapies for the treatment of autoimmune disease based on Kyverna's synthetic Treg platform and synNotch technology from Gilead subsidiary Kite Pharma. Kyverna will be responsible for conducting research activities and initial clinical studies through proof-of-concept. Gilead will be granted an option to continue to develop and potentially commercialize any product that comes from the research.

Under terms of this agreement, Gilead will pay Kyverna $17.5 million in upfront cash. Kyverna could earn an additional $570 million in development and commercialization milestones, depending on how the research goes.

Dominic Borie, chief executive officer of Kyverna, called it one of the most exciting times in the industry when a new modality has the potential to become the backbone of treatment for a variety of severe immune-related diseases. Borie is an immunologist and transplant surgeon who joins Kyverna from Horizon Therapeutics where he served as head of External Research and Development. Prior to Horizon, Borie served in numerous leadership functions within Genentech focused on global clinical development of immunology therapies including two anti-CD20 molecules (rituximab and obinutuzumab) in development for orphan immunology indications. Before that, Borie was with Amgen where he served as Medical Director and Global Development Leader for Inflammation.

In addition to Borie, the Kyverna team includes Jeffrey Greve, who will serve as the companys chief scientific officer. Prior to Kyverna, Greve founded and served as CSO of Delinia, an autoimmune disease company acquired by Celgene in 2017.

As part of the $25 million Series A, Fred Cohen, co-founder and senior managing director of Vida Ventures will serve as chairman of Kyvernas board of directors.

We are just beginning to see the potential for cell therapy and the opportunity to change the course of disease... At Vida, we have a long-standing commitment to advancing cell therapy. We believe the team at Kyverna, under Dominic's stewardship and in partnership with Dr. Greve, the architect of the Kyverna scientific platform, has the ability to develop a new class of therapies for serious autoimmune diseases, Cohen said in a statement.

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Gilead Backs Startup Kyverna Therapeutics with Financing, Collaborative Agreement - BioSpace

Attack of the Clones? Memory CD8+ T Cells Stalk the AD, PD Brain – Alzforum

14 Jan 2020

As if the neurodegenerative brain didnt have enough troubles, a study published in Nature on January 8 reports that it may be swarming with highly trained cellular henchmen. Researchers led by Tony Wyss-Coray at Stanford University found cytotoxic CD8+ T cells in the cerebrospinal fluid and brain tissue of people with Alzheimers and Parkinsons disease. Far from merely surveying the brain, they had multipliedclonally expanded, in immunology parlancesuggesting they were fighting specific antigens. To what were they responding? For most of the clones, this remains a mystery. However, a small proportion of T cells in three AD patients recognized a snippet of Epstein-Barr virus, a herpesvirus known to infect cells of the CNS.

This beautiful study shows, for the first time, a close association between T cells, cognition, and neurodegenerative disease in humans, wrote Jonathan Kipnis of University of Virginia in Charlottesville. These elegant findings on expansion of Epstein-Barr virus-reactive CD8 T cells in the CSF of AD patients are extremely interesting and intriguing, he added.

Neuroinflammation has moved to center stage in neurodegenerative disease research, but most work focuses on the innate, rather than adaptive, immune system. Still, evidence implicating the adaptive immune system has been quietly trickling in over the years. For example, scientists detected T cells specific for A and -synuclein in the blood of AD and PD patients, respectively (Bongioanni et al., 1997; Monsonego et al., 2003; Jun 2017 news).While dogma holds that T cells are scarce in the brain, a recently discovered lymphatic drainage system there carries T cells, making it clear that adaptive immune cells can, and do, frequent the CNS (Louveau et al., 2015; Oct 2017 news; Oct 2019 news). Some studies detected more T cells in the brains of people with neurodegenerative disease than in healthy brains (Togo et al., 2002; Town et al., 2005; Sept 2009 news).

In the new study, first author David Gate and colleagues set out to clarify what the adaptive immune system might do in Alzheimers. First, they took stock of immune cell populations in the blood, reporting that people with MCI or AD had more of a subtype of CD8+ T cells than did cognitively unimpaired controls. Specifically, high numbers of a subset of T effector memory cells expressing CD45RA, turned up in AD and MCI. Also known as T-EMRA cells, they are renowned for their killing efficiency, Gate told Alzforum. They rapidly dispense with any cells they recognize and also secrete a slew of proinflammatory cytokines.

In a separate cohort, the researchers found that the more circulating T-EMRA cells a person with AD or MCI had, the worse he or she performed on cognitive tests. Numbers of circulating T-EMRA cells predicted MCI or AD with 80 percent accuracy, suggesting that this particular subset of T cells in the blood was somehow tied to the neurodegenerative process in the brain.

Infiltrating the AD Brain. CD8+ T cells (green) congregate in blood vessels laden with cerebral amyloid angiopathy, and around Aplaques (red). [Courtesy of Gate et al., Nature, 2020.]

Could these cells also be in the brain, then? Immunohistochemistry on postmortem brain samples identified more CD8+ T cells in hippocampal parenchyma and adjacent leptomeninges of seven AD patients than of seven controls. The cells congregated around A plaques and neuronal processes. Gate also found numerous CD8+ T cells associated with the blood vessels affected by cerebral amyloid angiopathy in three AD patients, but found nary a T cell around the vasculature of controls. Gate did not measure other markers to determine whether these were T-EMRA cells.

Caught in the Act? A CD8+ T cell (red) in the hippocampus of an AD brain contains cytotoxic granules loaded with Granzyme A, a protein that kills target cells. [Courtesy of Gate et al., Nature, 2020.]

Gate spotted adaptive immune cells in the CSF as well. Most were T cells, but he was surprised to find 20 percent were CD8+, and of those, again 20 percent were T-EMRA. Were they just passing through, or carrying out an immunological hit? To find out, the researchers sequenced T cell receptor genes of individual T cells, which are unique due to the recombination that generates the TCRs. The existence of even two cells with identical receptor sequence indicates clonal expansion, and this occurs only when the killers encounter their cognate antigen (aka prey).

The scientists report evidence of numerous expanded clones in the CSF of 12 people with either MCI or AD (see image below). Clonal expansion was far less common among 10 controls. While one out of 10 healthy controls had a highly expanded clonei.e., one that comprised at least 3 percent of all TCR sequencesfour of six AD patients and one of five people with MCI did.

Moreover, individual clones detected in AD CSF had expanded to a greater degree than those from controls. One AD patient had a CD8+ T cell clone that comprised a whopping 44 percent of all CD8+ T cells in their CSF. Roughly two-thirds of all expanded CD8+ T cell clones belonged to the T-EMRA subset; the other third were T effector memory (T-EM) cells.

Clonal Expansion. Doughnuts show the T-cell pool in the CSF. While a majority of T cells from healthy controls were unique, i.e. not expanded (white), a majority of T cells in AD CSF had clonally expanded two to four times (orange), five to nine times (blue), or more than 10 times (green). For expanded clones, each colored wedge represents the percentage of total TCRs in the pool. Being too numerous, unique clones (white) are not represented by wedges. [Courtesy of Gate et al., Nature, 2020.]

The researchers also found more clonal expansions in the CSF of six people with PD, including two people with highly expanded clones, than in 10 controls. This suggested the phenomenon is not limited to AD.

The cells did not appear benign. Using single-cell RNA sequencing, the researchers found that the most highly expanded T-cell clones in the CSF expressed a bevy of pro-inflammatory cytokine and cytotoxic proteins, including Granzyme A, also made by CD8+ T cells in AD patients. The findings imply that these CNS T cells were killing cells that waved their specific antigenic flags in the brain, commented Terrence Town of the University of Southern California in Los Angeles. Granzyme A is the smoking gun, Town added.

To which antigens were these clones responding? For most of the clones, this question is unanswered. Employing TCR sequencing with a large helping of computational wizardry, the researchers identified T-cell clones in two people with AD and one with MCI that carried the T-cell receptors recognizing the same antigenan epitope from the EBNA3 protein in Epstein-Barr virus. EBV is a herpes virus known to infect the brain. Using an unbiased machine-learning approach, the researchers also picked up T cells in two other patients that reacted to yet another epitope from EBVthis one came from the EBV trans-activator protein BZLF1. No common expanded TCRs were found among controls.

The presence of the EBV-specific T cells is intriguing, but in no way establishes a link between EBV and AD, wrote Howard Weiner and Dennis Selkoe of Brigham & Womens Hospital in Boston in a joint comment to Alzforum. Weiner and Selkoe previously identified T cells specific for A and -synuclein in the blood of AD and PD patients.

The findings dont implicate EBV in the pathogenesis of AD. However, Gate speculated that stress and inflammation in the diseased brain could trigger reactivation of latent EBV, which could lead to recruitment of EBV-specific T cells and the slaughter of any infected neurons. Alternatively, or perhaps additionally, changes at the blood-brain barrier could let more T cells into the brain, Gate added. Town wondered whether damage to the integrity of the blood-brain barrier in vessels wracked with cerebral amyloid angiopathy could explain how CD8+ T cells gained access to those regions.

Guillaume Dorothe of INSERM in Paris said that the T-cell clones in the CSF could reflect clonal expansion that took place outside the brain. Perhaps the cells were responding to peripheral antigens, and then were unselectively recruited to the CSF of inflamed brain, he said. A direct comparison of T-cell clones in the blood and CSF of the same patients could help clarify this point, he added. Defining whether parenchymal T cells share antigen specificities with the clones patrolling the CSF will also be important, Dorothe noted. Regardless of what drove the cells into the CSF and brain, their presence supports the idea that T cells play some part in the neurodegenerative process, and that targeting them could alter the course of disease, he said. Dorothes previous studies in AD mice suggest that amplifying regulatory T cells, which control immune responses including T-cell immunity, slowed disease progression (Dansokho et al., 2016).

Gate did not test how many of the patients had been infected with EBV, nor directly measure EBV infection in brain samples. In a commentary accompanying the paper, Michael Heneka of the German Center for Neurodegenerative Diseases in Bonn urged caution in interpreting the findings. He noted that more than 95 percent of people are infected by EBV in their lifetime, but a previous study detected EBV DNA in only 6 percent of AD brains (Carbone et al., 2014).

Several studies have tied Alzheimers to various viruses, particularly herpes, though their connection to AD pathophysiology remains controversial (Itzhaki et al., 1997; Jun 2018 news;Jun 2018 news).Jessica Shugart

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Attack of the Clones? Memory CD8+ T Cells Stalk the AD, PD Brain - Alzforum

Black Country babies at risk as they miss out on vital jabs – expressandstar.com

The British Society for Immunology has urged the government to deliver on its promise to develop the UKs first vaccine strategy to protect communities against nasty diseases.

Young children should get the so-called six-in-one jab, which protects against six serious infections including polio, whooping cough and diphtheria, in the first few months of their lives.

But new Public Health England data shows that the uptake rate for the West Midlands over the period was 92.2 per cent the second-lowest of any region in the country. It compares to one of the best regions, the North East, where 95.4 per cent of children are immunised.

A further breakdown of the figures show that in Wolverhampton, just 89.7 per cent of babies who had their first birthday in the six months to September were vaccinated. It means 173 children missed out, with the area falling way short of the 95 per cent rate recommended by the World Health Organisation to prevent outbreaks.

In Walsall the figure was 93.1 per cent, with 131 children missing out, and in Sandwell it was 90.2 per cent, with 223 children not getting vaccinated. Dudley was one of the best areas, with 96 per cent of one-year-olds having the jabs, and only 75 babies missing out.

Over in Staffordshire it was 94.7 per cent, just shy of the recommended 95 per cent rate. About 224 children missed out on being vaccinated.

Low levels of vaccination coverage matter as it means these diseases have the potential to spread within our communities, infecting unvaccinated people, with young babies and people with compromised immune systems particularly at risk, said Dr Doug Brown of the British Society for Immunology.

We urge the new government to deliver on its promise to develop the UKs first vaccine strategy and to fully fund immunisation services to ensure our communities are protected against these preventable diseases.

But he also urged parents to make sure their children get the jabs, adding: If anyone is worried their child hasnt received all the doses of the six-in-one vaccine, they should make an appointment at their GP surgery. Its much better to get your child vaccinated than put them at risk.

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Black Country babies at risk as they miss out on vital jabs - expressandstar.com