title: Evidence of the Immune Relevance of Prevotella copri, a Gut Microbe, in Patients With Rheumatoid Arthritis.
abstract: Prevotella copri, an intestinal microbe, may overexpand in stool samples from patients with new-onset rheumatoid arthritis (RA), but it is not yet clear whether the organism has immune relevance in RA pathogenesis.
  
  
  
  HLA-DR-presented peptides (T cell epitopes) from P copri were sought directly in the patients' synovial tissue or peripheral blood mononuclear cell (PBMC) samples using tandem mass spectrometry. The antigenicity of peptides or their source proteins was examined in samples from the RA patients or comparison groups. T cell reactivity was determined by enzyme-linked immunospot assay; antibody responses were measured by enzyme-linked immunosorbent assay, and cytokine/chemokine determinations were made by bead-based assays. Serum and synovial fluid samples were examined for 16S ribosomal DNA for P copri using nested polymerase chain reaction analysis.
  
  
  
  In PBMCs, we identified an HLA-DR-presented peptide from a 27-kd protein of P copri (Pc-p27), which stimulated Th1 responses in 42% of patients with new-onset RA. In both new-onset RA patients and chronic RA patients, 1 subgroup had IgA antibody responses to either Pc-p27 or the whole organism, which correlated with Th17 cytokine responses and frequent anti-citrullinated protein antibodies (ACPAs). The other subgroup had IgG P copri antibodies, which were associated with Prevotella DNA in synovial fluid, P copri-specific Th1 responses, and less frequent ACPAs. In contrast, P copri antibody responses were rarely found in patients with other rheumatic diseases or in healthy controls.
  
  
  
  Subgroups of RA patients have differential IgG or IgA immune reactivity with P copri, which appears to be specific for this disease. These observations provide evidence that P copri is immune-relevant in RA pathogenesis.
authors.affiliation: Massachusetts General Hospital and, Harvard Medical School, Boston, Massachusetts.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Pianta
authors.affiliation: Massachusetts General Hospital and, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sheila
authors.initials: S
authors.lastname: Arvikar
authors.affiliation: Massachusetts General Hospital and, Harvard Medical School, Boston, Massachusetts.
authors.forename: Klemen
authors.initials: K
authors.lastname: Strle
authors.affiliation: Massachusetts General Hospital and, Harvard Medical School, Boston, Massachusetts.
authors.forename: Elise E
authors.initials: EE
authors.lastname: Drouin
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Boston University School of Medicine, Boston, Massachusetts.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Costello
authors.affiliation: Massachusetts General Hospital and, Harvard Medical School, Boston, Massachusetts.
authors.forename: Allen C
authors.initials: AC
authors.lastname: Steere
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000382:microbiology; D001426:Bacterial Proteins / Q000276:immunology*; D004275:DNA, Ribosomal / Q000235:genetics / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D058501:Enzyme-Linked Immunospot Assay; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009946:Organothiophosphorus Compounds / Q000276:immunology; D010455:Peptides / Q000276:immunology; D016133:Polymerase Chain Reaction; D018720:Prevotella / Q000235:genetics / Q000276:immunology*; D013582:Synovial Fluid / Q000378:metabolism; D013583:Synovial Membrane / Q000276:immunology*; D053719:Tandem Mass Spectrometry; D018417:Th1 Cells / Q000276:immunology; D055815:Young Adult
chemical_list: D001426:Bacterial Proteins; D004275:DNA, Ribosomal; D018984:Epitopes, T-Lymphocyte; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D009946:Organothiophosphorus Compounds; D010455:Peptides; C002301:phosfolan