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Oral mucosal breaks trigger anti-citrullinated bacterial and human protein antibody responses in rheumatoid arthritis.
Brewer, R Camille; Lanz, Tobias V; Hale, Caryn R; Sepich-Poore, Gregory D; Martino, Cameron; Swafford, Austin D; Carroll, Thomas S; Kongpachith, Sarah; Blum, Lisa K; Elliott, Serra E; Blachere, Nathalie E; Parveen, Salina; Fak, John; Yao, Vicky; Troyanskaya, Olga; Frank, Mayu O; Bloom, Michelle S; Jahanbani, Shaghayegh; Gomez, Alejandro M; Iyer, Radhika; Ramadoss, Nitya S; Sharpe, Orr; Chandrasekaran, Sangeetha; Kelmenson, Lindsay B; Wang, Qian; Wong, Heidi; Torres, Holly L; Wiesen, Mark; Graves, Dana T; Deane, Kevin D; Holers, V Michael; Knight, Rob; Darnell, Robert B; Robinson, William H; Orange, Dana E.
Afiliación
  • Brewer RC; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Lanz TV; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Hale CR; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Sepich-Poore GD; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Martino C; Department of Neurology, Medical Faculty Mannheim, University of Heidelberg, Mannheim 68167, Germany.
  • Swafford AD; Rockefeller University, New York City, NY 10065, USA.
  • Carroll TS; Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA.
  • Kongpachith S; Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA.
  • Blum LK; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA 92093, USA.
  • Elliott SE; Bioinformatics and Systems Biology Program, University of California, San Diego, La Jolla, CA 92093, USA.
  • Blachere NE; Center for Microbiome Innovation, University of California San Diego, La Jolla, CA 92093, USA.
  • Parveen S; Bioinformatics Resource Center, Rockefeller University, 1230 York Ave., New York, NY 10065, USA.
  • Fak J; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Yao V; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Troyanskaya O; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Frank MO; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Bloom MS; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Jahanbani S; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Gomez AM; Rockefeller University, New York City, NY 10065, USA.
  • Iyer R; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
  • Ramadoss NS; Rockefeller University, New York City, NY 10065, USA.
  • Sharpe O; Rockefeller University, New York City, NY 10065, USA.
  • Chandrasekaran S; Department of Computer Science, Rice University, Houston, TX 77005, USA.
  • Kelmenson LB; Department of Computer Science, Princeton University, Princeton, NJ 08544, USA.
  • Wang Q; Department of Computer Science, Princeton University, Princeton, NJ 08544, USA.
  • Wong H; Lewis-Sigler Institute of Integrative Genomics, Princeton University, Princeton, NJ 08544, USA.
  • Torres HL; Flatiron Institute, Simons Foundation, New York, NY 10010, USA.
  • Wiesen M; Rockefeller University, New York City, NY 10065, USA.
  • Graves DT; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Deane KD; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Holers VM; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Knight R; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Darnell RB; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
  • Robinson WH; VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
  • Orange DE; Division of Immunology and Rheumatology, Stanford University, Stanford, CA 94305, USA.
Sci Transl Med ; 15(684): eabq8476, 2023 02 22.
Article en En | MEDLINE | ID: mdl-36812347
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+HLADRhi and CD48highS100A2pos 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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Periodontales / Artritis Reumatoide Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Enfermedades Periodontales / Artritis Reumatoide Límite: Humans Idioma: En Revista: Sci Transl Med Asunto de la revista: CIENCIA / MEDICINA Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos