Evidence for Immune Relevance of Prevotella copri, a Gut Microbe, in Patients with Rheumatoid Arthritis
| Autor: | Klemen Strle, Sheila L. Arvikar, Qi Wang, Elise E. Drouin, Allen C. Steere, Catherine E. Costello, Annalisa Pianta |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Immunoglobulin A Adult Male Enzyme-Linked Immunospot Assay medicine.medical_treatment Immunology Prevotella Epitopes T-Lymphocyte Enzyme-Linked Immunosorbent Assay DNA Ribosomal Polymerase Chain Reaction Immunoglobulin G Article Arthritis Rheumatoid 03 medical and health sciences Young Adult Immune system Rheumatology Bacterial Proteins Tandem Mass Spectrometry Synovial Fluid medicine Immunology and Allergy Synovial fluid Humans Aged Aged 80 and over biology Synovial Membrane Organothiophosphorus Compounds Middle Aged Th1 Cells biology.organism_classification Gastrointestinal Microbiome 030104 developmental biology medicine.anatomical_structure Cytokine biology.protein Leukocytes Mononuclear Female Antibody Synovial membrane Peptides |
| Popis: | Objective 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. Methods 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. Results 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. Conclusion 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. |
| Databáze: | OpenAIRE |
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