ANNOUNCEMENT

NOBEL PRIZE 2026

This year's laureates, their fields, and the discoveries that earned them the prize.Live nowSee the winners
Moonbase
← Back to Awards
NIHNATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES

Insights into the origin of ACPAs in RA

Active
Institution
Johns Hopkins University, MD
Principal investigator
Felipe Andrade
Funding
$188K
Duration
2025–2026
Open portfolio

Moonbase score

Still being scored

Abstract

PROJECT SUMMARY/ABSTRACT Citrullination is a physiologic post-translational modification found across multiple normal human tissues. Why this modification is the most important target of antibodies in rheumatoid arthritis (RA) is unknown. While the pathogenic role of anti-citrullinated protein antibodies (ACPAs) remains uncertain, the striking association between ACPAs and RA has raised the possibility that understanding the origin of these antibodies may shed light on the cause of RA. Interestingly, our preliminary studies provide evidence that ACPAs may originate from a distinct antibody targeting a different but structurally similar modification, known as carbamylation. Our overarching hypothesis is that ACPAs can arise during affinity maturation of germline encoded antibodies to carbamylated proteins. In this proposal, we will use RA-derived monoclonal ACPAs to support or discard this novel hypothesis. If the proposal is successful, this work may uncover a mechanism for why citrullinated proteins become immunogenic and potentially to support germline encoded antibodies to carbamylated proteins as initial players in the development of RA.

LOADING MOONBASE SCORE

NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASESR21Hypersensitivity, Autoimmune, and Immune-mediated Diseases Study Section[HAI]encodedmodificationorigingermlineantibodiespathogenic rolenormal humansuccessful work

Questions for Johns Hopkins University

Answered by the team behind this research.

No questions yet. Sign in to ask the first one

Related grants

Same researchers, same institution, same topic, scored first.