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Insights into the origin of ACPAs in RA

Award Number: R21AI188438
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 01/09/2025
PERIOD OF PERFORMANCE END DATE: 12/31/2026

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Insights into the origin of ACPAs in RA - 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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = $232,875 )
2026	2026	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	2	1/2/2026	NON-COMPETING CONTINUATION	$232,875
														Subtotal = $232,875

Issue Date FY: 2025 ( Subtotal = $187,938 )
2025	2025	THE JOHNS HOPKINS UNIVERSITY	3400 N CHARLES ST	BALTIMORE	MD	21218	BALTIMORE CITY	USA	Allergy and Infectious Diseases Research	000	1	1/9/2025	NEW	$187,938
														Subtotal = $187,938

Grand Total All Awards = $420,813

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Insights into the origin of ACPAs in RA

Award Number: R21AI188438

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 01/09/2025

PERIOD OF PERFORMANCE END DATE: 12/31/2026

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