Publication: “Immunomodulatory drugs have divergent effects on humoral and cellular immune responses to SARS-CoV-2 vaccination in people living with rheumatoid arthritis”

Jenna Benoit (PhD candidate) has published her first, first author paper characterizing how immune responses to vaccination differ in people living with rheumatoid arthritis. We found some interesting new drug-immune interactions.

See the full paper here.

See thread here: https://bsky.app/profile/msmacrophage.bsky.social/post/3kh2uswvqtm2u

or below….

New paper alert! @jennabenoit.bsky.social and team studied COVID-19 vaccinations in people living with rheumatoid arthritis who are on immunosuppressive drugs and found some interesting, and to our knowledge, unknown effects of specific drugs 1/n

Almost all studies of vaccine immunogenicity (i.e., how strong an immune response is to a vaccine) focus on antibody responses. Measuring the amount of antibodies produced is cheap and (relatively) easy; however, in the Omicron-era these are less predictive of protection than you might think 2/n

When investigating anti-receptor binding domain (RBD) antibodies @jennabenoit.bsky.social and team found that -unsurprisingly- people living with RA and men had lower antibody responses (men have lower antibody responses to vaccination in general), and people with COVID had higher responses (i.e., that hybrid immunity you’ve heard so much about) 3/n

What caused these lower antibody responses? DMARDs (disease modifying anti-rheumatic drugs),and anti-TNF were not associated with lower antibody levels, the effect of steroids was not significant, but costimulation inhibitors reduced antibody levels 4/n

Important caveat: The effect of co-stimulation inhibitors was about the same as being a biologic male, so whether this reduction is associated with increased risk of infection or not is not something we can comment on 5/n.

We didn’t see an effect of drugs on neutralizing antibodies (i.e., antibodies that bind the virus really well and prevent it from entering us), but we did not have enough people on some of the drugs to really investigate this 6/n.

My favourite part: CD4+ and CD8+ T cell responses to vaccination are much, much harder to measure (each dot on the graph costs about $350 and 3+ hrs of time – hence the ‘team’ I keep mentioning) but we know that they are important for preventing infection.7/n

We found that people living with RA had lower CD4+ T cell responses (= ‘helper’ cells that support many aspects of the immune response to infection & vaccination), those who had had COVID were higher – more of that hybrid immunity you’ve heard about. 8/n

BUT even though we had a small number of people on JAK inhibitors, those who were on them had markedly lower CD4+ responses. The effect of co-stimulation inhibitors was not as apparent – but again low numbers of participants so hard to say. 9/n

Speculative side note: We use influenza vaccine as a control. Everyone has had exposure as kids so this measures a memory response made prior to having been vaccinated. Co-stim inhibitors don’t affect influenza but JAK inhibitors do – therefore no defect in pre-drug immune responses? 10/n

CD8+ T cell responses (‘killers’ of virus infected cells), were higher in men (previously known), and didn’t seem to be lower in most drugs, except maybe steroids. 11/n

Caveats: Our study was small and due to the fact we were measuring 1,2,3 doses, we were recruiting fast and furious and didn’t capture as many people on some of the drugs as we would have liked,so all results need to be replicated. 12/n

Clinical relevance: Some of these drugs are associated with increased risk of severe disease (see text for references) and by learning which aspects of the immune response they affect, we learn which aspects of the immune response are required for a successful vaccine. 13/n

Deepest appreciation for our research participants, the Canadian Arthritis Patient Alliance (see website for talks on this topic), the SUCCEED investigator team, our technical staff, fundign from the Public Health Agency of Canada, and you for reading to 14/n

Congratulations to Dessi Loukov on successfully defending her PhD!

Congratulations to the newly minted Dr. Loukov on successfully defending her thesis entitled “Age-Associated Inflammation impairs Myeloid Development and Monocyte & Macrophage Function”!

The newly minted Dr. Loukov drinks from the chalice.

Dessi celebrates her thesis defence with one of her mentors Dr. Mark McDermott.

Two doctors.

PDF and PhD position available.

The Bowdish lab is looking for new members to join our team! We currently have an opening for a post-doctoral fellow and a graduate student.

The PDF will project will involve investigating how the upper respiratory tract microbiome changes with age and declining immune function. Applicants must have a strong publication record in the field of immunology, microbiology, systems biology or molecular biology and applicants eligible for PDF funding from http://fhs.mcmaster.ca/mgdfa/ are particularly encouraged to apply (see link for eligibility). Experience in analysis of the microbiome or statistics of large/complex datasets are assets. Please provide a c.v. and a cover letter detailing your interest in the lab that includes contact details for references.

The graduate student position will be studying why aging macrophages are less able to kill bacteria. Applicants interested in beginning studies in January, May or Sept 2018 will be considered. Students aiming to pursue a PhD are preferred but exceptional MSc applicants will be considered. Previous research experience is strongly preferred. Candidates must have relevant courses in molecular/cellular biology, biochemistry, immunology or microbiology. Please include a transcript, a cover letter outlining your previous research experience and a list of references. Foreign students must have a scholarship to be considered.

Come join our strong team!

Bowdish lab scholarship winners 2015/2016: Netusha Thevaranjan (CIHR-PhD), Avee Naidoo (CIHR-PhD), Kyle Novakowski (NSERC-PhD), Pat Schenck (CIHR-PhD), Dessi Loukov (CIHR-PhD), Justin Boyle (NSERC-MSC).

The Bowdish lab is the strongest lab at McMaster and we have the scholarship winners to prove it!

Who’s got the strongest lab at McMaster? I do! We’ve had a great run of success at the Bowdish lab with fully all of our students receiving prestigious scholarships! And that’s not to mention our other successes such as our summer scholarship winners (Jason Fan – IIDR), our students who got their degree and moved on to great things (Dr. Fan Fei – manager of Mass Spec facility, Dr. Mike Dorrington – PDF at the NIH), and our PDF, Dr. Chris Verschoor who got a faculty position!

Who's got the strongest lab at McMaster? I do! Bowdish lab scholarship winners 2015/2016: Netusha Thevaranjan (CIHR-PhD), Avee Naidoo (CIHR-PhD), Kyle Novakowski (NSERC-PhD), Pat Schenck (CIHR-PhD), Dessi Loukov (CIHR-PhD), Justin Boyle (NSERC-MSC).

Bowdish lab scholarship winners 2015/2016: Netusha Thevaranjan (CIHR-PhD), Avee Naidoo (CIHR-PhD), Kyle Novakowski (NSERC-PhD), Pat Schenck (CIHR-PhD), Dessi Loukov (CIHR-PhD), Justin Boyle (NSERC-MSC).

Publication: Tumor necrosis factor drives increased splenic monopoiesis in old mice

bowdish

PhD student Dessi Loukov in the lab of Dr. Dawn Bowdish, recently published a study showing that splenomegaly in old mice is a result of extramedullary hematopoiesis, and that this increased monopoiesis is driven by age-associated increase in TNF. The study compared changes in the microarchitecture and composition of the spleen in old and young mice and found that in old mice, there was an increase in the size and cellularity of the red pulp (the site of hematopoiesis of myeloid precursors). To study the role of TNF in the development of extramedullary hematopoiesis, they used TNF KO mice and found that these mice did not have increased extramedullary monopoiesis. Furthermore, they demonstrated that increased splenic myelopoiesis was a result of the aging microenvironment. This work suggests that strategies which aim to decrease the inflammatory microenvironment that comes with aging, would be effective in reducing inflammatory diseases propagated by cells of the myeloid lineage. Read More

 

The Bowdish lab has a new PhD student! Congrats Avee!

 

 

Avee Naidoo successfully passed her transfer exam today. She now joins the ranks of Fan Fei, Mike Dorrington, Kyle Novakowski, Dessi Loukov, Sara Makaremi, and Pat Schenck as part of the Bowdish lab PhD posse. Well done Avee!

 

Avee-med

Becoming a PhD student in the Bowdish lab is a family affair. Junior lab members  sent their favourite stuffie in to wish Avee luck. It must have worked as she aced it!Becoming a PhD student in the Bowdish lab is a family affair. Junior lab members sent their favourite stuffie in to wish Avee luck. It must have worked as she aced it!

...and a little lab humour. We have both skilled scientists (see picture at bottom) and skilled artists (see whiteboard) in our lab.

…and a little lab humour. We have both skilled scientists (see picture at bottom) and skilled artists (see whiteboard) in our lab.

Alicja Puchta recognized for teaching excellence.

Alicja Puchta (PhD candidate) was recognized for her excellence in graduate teaching at the Faculty of Health Sciences Research Plenary. Alicja has been a dedicated and passionate teaching assistant for both anatomy and immunology courses during the course of her MSc and PhD degrees. She has been asked for by name by multiple instructors and is a clear favourite with her students. Congratulations Alicja!

Alicja Puchta recognized for her excellent TAing

Alicja Puchta recognized for her contributions to teaching. D. Bowdish, Alicja Puchta and Catherine Hayward, Dean of Graduate Studies.