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Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis

Authors :
R. Camille Brewer
Tobias V. Lanz
Caryn R. Hale
Gregory D. Sepich-Poore
Cameron Martino
Austin D. Swafford
Thomas S. Carroll
Sarah Kongpachith
Lisa K. Blum
Serra E. Elliott
Nathalie E. Blachere
Salina Parveen
John Fak
Vicky Yao
Olga Troyanskaya
Mayu O. Frank
Michelle S. Bloom
Shaghayegh Jahanbani
Alejandro M. Gomez
Radhika Iyer
Nitya S. Ramadoss
Orr Sharpe
Sangeetha Chandrasekaran
Lindsay B. Kelmenson
Qian Wang
Heidi Wong
Holly L. Torres
Mark Wiesen
Dana T. Graves
Kevin D. Deane
V. Michael Holers
Rob Knight
Robert B. Darnell
William H. Robinson
Dana E. Orange
Source :
Science Translational Medicine. 15
Publication Year :
2023
Publisher :
American Association for the Advancement of Science (AAAS), 2023.

Abstract

Periodontal disease is more common in individuals with rheumatoid arthritis (RA) who have detectable anti-citrullinated protein antibodies (ACPAs), implicating oral mucosal inflammation in RA pathogenesis. Here, we performed paired analysis of human and bacterial transcriptomics in longitudinal blood samples from RA patients. We found that patients with RA and periodontal disease experienced repeated oral bacteremias associated with transcriptional signatures of ISG15 + HLADR hi and CD48 high S100A2 pos monocytes, recently identified in inflamed RA synovia and blood of those with RA flares. The oral bacteria observed transiently in blood were broadly citrullinated in the mouth, and their in situ citrullinated epitopes were targeted by extensively somatically hypermutated ACPAs encoded by RA blood plasmablasts. Together, these results suggest that (i) periodontal disease results in repeated breaches of the oral mucosa that release citrullinated oral bacteria into circulation, which (ii) activate inflammatory monocyte subsets that are observed in inflamed RA synovia and blood of RA patients with flares and (iii) activate ACPA B cells, thereby promoting affinity maturation and epitope spreading to citrullinated human antigens.

Subjects

Subjects :
General Medicine

Details

ISSN :
19466242 and 19466234
Volume :
15
Database :
OpenAIRE
Journal :
Science Translational Medicine
Accession number :
edsair.doi...........fe98296461d8cd7e49e173f6484eb349
Full Text :
https://doi.org/10.1126/scitranslmed.abq8476