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

Publication: Monocyte activation is elevated in women with knee-osteoarthritis and associated with inflammation, BMI and pain.

Dr. Dawn Bowdish and her PhD student Dessi Loukov  collaborated with Dr. Monica Maly and Sara Karampatos (Rehabilitation Science) and found that monocytes were more activated and pro-inflammatory in women with osteoarthritis, and that elevated inflammation and body mass index were associated with increased monocyte activation. Further, the team found that women with osteoarthritis and more activated monocytes experienced worse pain than individuals with less activated monocytes. These findings highlight the importance of modulating inflammation and body mass to manage osteoarthritis and open up new avenues for therapeutic research.

Read the full publication in the Osteoarthritis Research Society International (OARSI) Journal

As featured in Eureka Alert: https://www.eurekalert.org/pub_releases/2017-11/mu-rul112717.php

A guide to Bioinformatics for Immunologists

Congratulations to Fiona Whelan (MSc, Bowdish lab; PhD student, Surette lab) for publishing the review article “A guide to bioinformatics for immunologists” in Frontiers Immunology. The idea of this article spawned from the research that Fiona conducted in the Bowdish lab on the elucidation of the evolutionary history and relationships between the members of the class A scavenger receptors, proteins required for host defense and homeostasis. During this time, Fiona used multiple bioinformatic techniques and tools to form hypotheses as to the function of one under-annotated member of this family, SCARA3.  Even though most of these tools are easy-to-use and require little computational knowledge, Fiona and Dawn discovered through their interactions with other immunologists that these tools were being under utilized.  Thus, they decided to write a review of how bioinformatic techniques can help the average immunologist in their quest for knowledge about the structure of their protein of interest, how to find SNPs that may correlate with disease phenotype, and how to conduct sequence alignments in order to find areas that are conserved across various genes.

This review article is written as a case study that follows Fiona’s research into SCARA3 that begins with obtaining the NCBI Reference FASTA sequence of the protein, predicting post-translational modifications, identifying conserved motifs, hypothesizing as to the structure of the protein, examining SCARA3’s transcriptomic profile in different immunological cell types, and analyzing any potential SNPs within the DNA sequence of SCARA3 that may correlate with disease. The article is written with the immunologist in mind and includes the use of only “point and click” tools that require no computational background whatsoever.

Is Fiona’s paper is Open Access? Of course it is! Enjoy reading it here and reading the description on the Surette lab website here.

The laboratories of both Dr. Bowdish and Dr. Surette are always interested in undergraduate and graduate students interested in exploring the impact bioinformatics can have on immunological and microbiological research.

Congratulations to Julie Kaiser on successfully defending her MSc!

Bowdish lab associate member (technically she’s supervised by Dr. Mike Surette but we think of her as one of our own), Julie Kaiser, successfully defended her MSc thesis “Host responses to the Strepotococcus Milleri Group”. To see a photo of Julie in her post exam bliss/haze click here. Julie is moving on to a PhD at UWO in Dr. Dave Heinrichs lab. We’re sending Dave on of our best & brightest – we expect a thank you card any day now.

The Bowdish lab enters a collaborative agreement with Qu Biologics.

The lab of Dr. Dawn Bowdish at the McMaster University Immunology Research Centre (MIRC) has recently begun collaboration with the Vancouver-based pharmaceutical company Qu Biologics on preclinical studies investigating the role of macrophage dysfunction in chronic inflammation.

Qu Biologics has developed Site Specific Immunomodulators (SSIs), which aim to “reboot” the body’s innate immune system in targeted organs or tissues to reverse chronic inflammation.

“Macrophages are important cells of the innate immune system. There is growing evidence that macrophage dysfunction underlies many important common chronic diseases, including cancer and autoimmune disease,” said Dr. Hal Gunn, CEO of Qu Biologics. “This collaboration will be invaluable to assist in our understanding of the benefits of SSI therapy on macrophage function as it relates to chronic inflammation and immune dysfunction.” Dr. Gunn added.

The studies will test whether a lung-specific SSI therapy can restore normal lung and bone marrow-derived macrophage function using a variety of in vivo and in vitro assays.

Dr. Bowdish adds “This is an ambitious and exciting project that takes a fundamentally different approach to tackling the problem of chronic inflammation, which has been very resistant to therapeutic intervention. My team is thrilled to be working together on a problem that affects the lives of so many Canadians.”  This work capitalizes on the resources and immunology expertise of the McMaster Immunology Research Centre and Dr. Bowdish’s research interests in how inflammation impairs macrophage function.

About Qu Biologics

Qu Biologics develops Site Specific Immunomodulators (SSI), a novel class of immunotherapies that aim to reboot the body’s immune system. SSIs are designed to stimulate an immune response in targeted organs or tissues to potentially reverse the chronic inflammation underlying many conditions including cancer and autoimmune disease. The company recently launched a Phase 1/2 clinical trial to research SSI therapy for the treatment of Crohn’s disease.

Backed by a prestigious group of scientific advisors and board members, Qu Biologics is led by a management team that includes co-founder and CEO Dr. Hal Gunn, a physician and expert on the body’s immune response to chronic disease; and Chief Medical Officer Dr. Simon Sutcliffe, former CEO of the BC Cancer Agency and a distinguished clinician, scientist and leader in cancer control in Canada and internationally.  For more information, visit www.qubiologics.com and www.qucrohnstrial.com.

For more details and to see the original press release here:

http://www.qubiologics.com/qu-biologics-begins-research-with-mcmaster-university-to-study-chronic-inflammation-associated-with-macrophage-dysfunction/

 

 

Collaborator update: Fan Fei wins “Glasgow Polyomics & University of Strathclyde Young Scientist Award” at the 9th Annual Conference of the Metabolomics Society!

Fan Fei (PhD candidate), under the supervision of Dr. Brian McCarry, and in conjunction with Bowdish lab undergraduate Keith Lee, studies age related changes in the inflammatory response from a metabolomics perspective. Funded by the Russell Bell Travel Scholarship award, she attended the  9th Annual conference of the Metabolomics Society. July 1-4, 2013, SECC Glasgow. She won the “Glasgow Polyomics & University of Strathclyde Young Scientist Award” for outstanding poster presentation of research in the field of metabolomics at the Metabolomic Conference 2013 in Glasgow Scotland for her work “Comprehensive Metabolomic Analysis Reveals Major Differences in the Macrophage Inflammatory Response Between Young and Aged Mice”. Way to go Fan!

 

Dawn receives funding from the IIDR to study the role of macrophages in pneumococcal disease

The IIDR has awarded the Bowdish lab seed money to study the role of macrophages in host response to colonization by Streptococcus pneumoniae. S. pneumoniae infections can range from treatable (respiratory tract infections, otitis) to life-threatening (meningitis, sepsis). The introduction of the pneumococcal conjugate vaccine (PCV) has shifted the epidemiology of S. pneumoniae infections but not eliminated them.  In humans, colonization of the upper respiratory tract is the initial step in pathogenesis. This is accompanied by a robust antibody response, which is generally believed to be required for clearance (and thus prevention of infection); however, data for this is not supported by clinical observations in which high levels of antibodies are not associated with clearance or in which immunodeficient patients susceptible to pneumococcal infections can produce robust anti-pneumococcal antibody responses while still being prone to recurrent systemic infections.  The aim of this project is to assess the importance of macrophages in the recognition and clearance of S. pneumoniae in the upper respiratory tract.   This work will be done in collaboration with Prof. Jeffrey Weiser at the University of Pennsylvania who is a world leader in the field of S. pneumoniae pathogenesis. Dawn will be travelling to his lab in July to learn from his lab members.  The Bowdish lab is currently recruiting graduate students and post-docs who are interested in the host response to S. pneumoniae infection and colonization.