IgM and IgA Rheumatoid Factors Purified from Rheumatoid Arthritis Sera Boost the Fc Receptor– and Complement-Dependent Effector Functions of the Disease-Specific Anti–Citrullinated Protein Autoantibodies
| Autor: | Mireille Sebbag, Géraldine Offer, Cyril Clavel, Guy Serre, Florence Anquetil |
|---|---|
| Přispěvatelé: | CARBILLET, Véronique, Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Toulouse [Toulouse] |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Lipopolysaccharides
Male Fc receptor Arthritis Receptors Fc MESH: Inflammation / chemically induced MESH: Lipopolysaccharides / pharmacology MESH: Immunoglobulin G* / isolation & purification Arthritis Rheumatoid MESH: Complement Activation / drug effects 0302 clinical medicine MESH: Macrophages / pathology MESH: Immunoglobulin G* / pharmacology immune system diseases MESH: Arthritis Rheumatoid / immunology [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Arthritis Rheumatoid / pathology Immunology and Allergy MESH: Immunoglobulin M* / pharmacology skin and connective tissue diseases Complement Activation 0303 health sciences Synovitis biology Chemistry MESH: Complement System Proteins / immunology MESH: Inflammation / pathology MESH: Macrophages / immunology [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases MESH: Receptors Fc / immunology Cytokines Tumor necrosis factor alpha Female medicine.symptom musculoskeletal diseases MESH: Synovitis / immunology Immunology Inflammation MESH: Complement Activation / immunology 03 medical and health sciences Immune system Rheumatoid Factor medicine Humans MESH: Rheumatoid Factor* / isolation & purification MESH: Cytokines / immunology MESH: Synovitis / pathology 030304 developmental biology MESH: Inflammation / immunology MESH: Humans Macrophages Autoantibody Complement System Proteins MESH: Immunoglobulin M* / isolation & purification medicine.disease MESH: Male Complement system Immunoglobulin M Immunoglobulin G biology.protein TLR4 MESH: Rheumatoid Factor* / pharmacology MESH: Female 030215 immunology |
| Zdroj: | Journal of Immunology Journal of Immunology, 2015, 194 (8), pp.3664-3674. ⟨10.4049/jimmunol.1402334⟩ Journal of Immunology, Publisher : Baltimore : Williams & Wilkins, c1950-. Latest Publisher : Bethesda, MD : American Association of Immunologists, 2015, 194 (8), pp.3664-3674. ⟨10.4049/jimmunol.1402334⟩ |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.1402334⟩ |
| Popis: | Rheumatoid factors (RF) and the disease-specific anti–citrullinated protein autoantibodies (ACPA) coexist in the joints of rheumatoid arthritis (RA) patients where they probably contribute to synovitis. We investigated the influence of IgM and IgA RF on the FcR- and complement-dependent effects of ACPA immune complexes (ACPA-IC). When stimulated by ACPA-IC formed in the presence of IgM RF or IgA RF fractions purified from RA serum pools, M-CSF–generated macrophages skewed their cytokine response toward inflammation, with increases in the TNF-α/IL-10 ratio and in IL-6 and IL-8 secretion, and decreases in the IL-1Ra/IL-1β ratio. In the IgM RF-mediated amplification of the inflammatory response of macrophages, the participation of an IgM receptor was excluded, notably by showing that they did not express any established receptor for IgM. Rather, this amplification depended on the IgM RF-mediated recruitment of more IgG into the ACPA-IC. However, the macrophages expressed FcαRI and blocking its interaction with IgA inhibited the IgA RF-mediated amplification of TNF-α secretion induced by ACPA-IC, showing its major implication in the effects of RF of the IgA class. LPS further amplified the TNF-α response of macrophages to RF-containing ACPA-IC. Lastly, the presence of IgM or IgA RF increased the capacity of ACPA-IC to activate the complement cascade. Therefore, specifically using autoantibodies from RA patients, the strong FcR-mediated or complement-dependent pathogenic potential of IC including both ACPA and IgM or IgA RF was established. Simultaneous FcR triggering by these RF-containing ACPA-IC and TLR4 ligation possibly makes a major contribution to RA synovitis. |
| Databáze: | OpenAIRE |
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