Reuben McGregor

Acute rheumatic fever is an autoinflammatory disease

@njmoreland.bsky.social, @rhcmcg.bsky.social report widespread antibody heterogeneity, yet identify a protein expressed in cardiac muscle as an immunodominant autoantigen: doi.org/10.1172/jci....

@njmoreland.bsky.social
@laurencarlton.bsky.social
@insight.jci.org

Summary: Our data supports a model of "epitope spreading" in ARF.

This complexity helps explain why diagnosing and treating the condition is difficult. We likely need to look at multiple pathway level dysfunction rather than single markers.

Read the full paper here doi.org/10.1172/jci....

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Key Finding 3: While patients targeted different specific proteins, these targets converged on shared biological pathways: e.g. sarcomere structure and heart morphogenesis.

The immune system appears to target some common functional areas, but through different antigens.

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Key Finding 2: Despite the variation, we identified specific new targets.

notably, we found enrichment for PPP1R12B, a regulatory subunit of the myosin phosphatase complex expressed in cardiac muscle, alongside previously known collagen targets.

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Key Finding 1: "Public epitopes"—targets shared by many distinct patients—were rare, comprising less than 1% of enriched peptides.

This suggests ARF auto-immune pathogenesis is not driven by a single common antigen, but potentially by a broader breakdown in tolerance.

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New paper out in JCI Insight:
PhIP-Seq uncovers marked heterogeneity in Acute Rheumatic Fever Autoantibodies.

ARF is a serious sequela of Strep A infection. While autoantibodies are known to drive pathogenesis, the specific human protein targets remain unclear.

Link: doi.org/10.1172/jci....
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This deep dive into the clinical phenotype of rheumatic fever highlights extreme diversity in presenting symptoms. An important observation from the START study, and highlights why better diagnostic tests are needed 🧪 @annapralph.bsky.social @rhcmcg.bsky.social

bmjopen.bmj.com/content/15/7...

Decline of antibodies to major viral and bacterial respiratory pathogens during the COVID-19 pandemic Antibodies to respiratory syncytial virus and Group A Streptococcus waned significantly in a longitudinal cohort throughout the pandemic. This waning may h

Following relaxation of #COVID19 restrictions surges in infections from respiratory pathogens like RSV and #StrepA have been seen in many countries including Aotearoa New Zealand.
Did waning immunity contribute? We explored this concept in our latest work, see 🧵 academic.oup.com/jid/advance-...

Finally jumping into 🦋 - and what better way to do than highlighting this super thread. Wonderful to have been involved in this study with our Strep A friends across the Tasman

🎉 I'm a #newPI , and I'm so excited to share our new paper out in Nature Comms today! 🧵
rdcu.be/d2gBV
Quick intro for the new followers:
I'm from Monash Uni in Melbourne, and we study T and B cell responses to viruses, bacteria & parasites with the goal of improving vaccines. #ImmunoSky #MicroSky