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Immune complexes from SLE sera induce IL10 productionfrom normal peripheral blood mononuclear cells by anFcvicious cycle maintaining B cell hyperactivity in SLEgRII dependent mechanism: implications for a possible vicious cycle maintaining B cell hyperactivity in SLE
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Autoimmunitet)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Autoimmunitet)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology. (Autoimmunitet)
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology, Clinical Immunology.
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2003 (English)In: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 62, no 1, 37-42 p.Article, review/survey (Other academic) Published
Abstract [en]

BACKGROUND: Raised interleukin (IL)6 and IL10 levels are thought to contribute to the pathogenesis of systemic lupus erythematosus (SLE) by enhancing autoantibody production and immune complex (IC) formation. These immune complexes can then stimulate cellular reactions through Fc and complement receptors. OBJECTIVE: To investigate whether circulating SLE ICs stimulate type 2 cytokine production. METHODS: Twenty serum samples from patients with active SLE were compared with sera from 18 healthy controls. Sera and polyethylene glycol (PEG) precipitates from sera were added to peripheral blood mononuclear cell (PBMC) cultures, and the production of IL10 and IL6 was investigated by enzyme linked immunospot assay (ELISPOT) and enzyme linked immunosorbent assay (ELISA). Fc gamma receptor (FcgammaR) antibodies were used in blocking experiments, and flow cytometry was used to assess the correlation between monocyte FcgammaR expression and IC-induced cytokine production. RESULTS: Ten per cent dilutions of the SLE sera induced a significantly increased number of IL10-producing cells in comparison with control sera (median, 11.75 v 1.25 spot forming cells/50 000 PBMC; p<0.0001). PEG precipitates from SLE sera also induced significantly increased levels of IL10 (p=0.016) and IL6 (p=0.042) in comparison with control PEG precipitates. IL10 production induced by SLE PEG precipitates or by artificial ICs could be blocked by anti-FcgammaRII antibodies, and the FcgammaRII expression on CD14+ monocytes correlated with the IC-induced production of IL10 and IL6. CONCLUSIONS: SLE sera stimulate IL10 and IL6 production from PBMC, and this effect is at least partly explained by precipitable ICs acting through FcgammaRII. This effect provides a possible mechanism for the enhanced production of IL10 in SLE, whereby B cell activation, antibody production, IC stimulated monocytes/macrophages, and type 2 cytokines create a vicious cycle that may help to maintain B cell hyperactivity in SLE.

Place, publisher, year, edition, pages
2003. Vol. 62, no 1, 37-42 p.
Keyword [en]
Arthritis; Rheumatoid/*diagnosis/immunology, Autoantibodies/*blood, Citrulline/*immunology, Humans, Prognosis, Rheumatoid Factor/blood, Sensitivity and Specificity
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Medical and Health Sciences
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URN: urn:nbn:se:uu:diva-64398DOI: 10.1136/ard.62.1.37PubMedID: 12480667OAI: oai:DiVA.org:uu-64398DiVA: diva2:92309
Available from: 2008-01-28 Created: 2008-01-28 Last updated: 2017-11-30Bibliographically approved

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Rönnelid, JohanMathsson, LindaNilsson Ekdahl, KristinaNilsson, Bo

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