학술논문
Antibodies to a Citrullinated Porphyromonas gingivalis Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology
Document Type
article
Author
Natalia Sherina; Charlotte de Vries; Nastya Kharlamova; Natalie Sippl; Xia Jiang; Boel Brynedal; Elin Kindstedt; Monika Hansson; Linda Mathsson-Alm; Lena Israelsson; Ragnhild Stålesen; Saedis Saevarsdottir; Rikard Holmdahl; Aase Hensvold; Gunnar Johannsen; Kaja Eriksson; Federica Sallusto; Anca I. Catrina; Johan Rönnelid; Caroline Grönwall; Tülay Yucel-Lindberg; Lars Alfredsson; Lars Klareskog; Luca Piccoli; Vivianne Malmström; Khaled Amara; Karin Lundberg
Source
Frontiers in Immunology, Vol 13 (2022)
Subject
Language
English
ISSN
1664-3224
Abstract
Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium Porphyromonas gingivalis to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the gum mucosa. To address this hypothesis, we investigated the antibody response to a citrullinated P. gingivalis peptide in relation to the autoimmune ACPA response in early RA, and examined citrulline-reactivity in monoclonal antibodies derived from human gingival B cells. Antibodies to a citrullinated peptide derived from P. gingivalis (denoted CPP3) and human citrullinated peptides were analyzed by multiplex array in 2,807 RA patients and 372 controls; associations with RA risk factors and clinical features were examined. B cells from inflamed gingival tissue were single-cell sorted, and immunoglobulin (Ig) genes were amplified, sequenced, cloned and expressed (n=63) as recombinant monoclonal antibodies, and assayed for citrulline-reactivities by enzyme-linked immunosorbent assay. Additionally, affinity-purified polyclonal anti-cyclic-citrullinated peptide (CCP2) IgG, and monoclonal antibodies derived from RA blood and synovial fluid B cells (n=175), were screened for CPP3-reactivity. Elevated anti-CPP3 antibody levels were detected in RA (11%), mainly CCP2+ RA, compared to controls (2%), p