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Immune complexes from rheumatoid arthritis synovial fluid induce FcγRIIa dependent and rheumatoid factor correlated production of tumour necrosis factor-α by peripheral blood mononuclear cells
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology.
2006 In: Arthritis Research and Therapy, ISSN 16569263, Vol. 8, no 3, R64- p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2006. Vol. 8, no 3, R64- p.
URN: urn:nbn:se:uu:diva-95381OAI: oai:DiVA.org:uu-95381DiVA: diva2:169566
Available from: 2007-01-19 Created: 2007-01-19Bibliographically approved
In thesis
1. Immune Complex Regulated Cytokine Production in Rheumatic and Lymphoproliferative Diseases
Open this publication in new window or tab >>Immune Complex Regulated Cytokine Production in Rheumatic and Lymphoproliferative Diseases
2007 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Immune complexes (ICs) are produced during normal immune responses and facilitate clearance of foreign antigens. ICs not efficiently cleared from the circulation can cause tissue damage. This might happen if ICs are formed with autoantibodies and autoantigens. Well described effects of ICs are neutralization of antigen, classical complement activation or FcR-mediated phagocytosis, whereas cytokine inducing effects of ICs in human clinical settings are less well described. I have investigated cytokine-inducing properties in vitro of ICs from patients with rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and cryoglobulinemia in association with lymphoproliferative diseases.

Cryoglobulin (CG)-induced cytokine production varied with changes in temperature and ionic strength in parallel to CG precipitation. IgG CG-induced cytokine production was also mediated via FcγIIa on monocytes. Blockade of the complement system, resembling the in vivo situation of complement consumption in CG-associated diseases, increased IgG CG induced IL-10 and decreased TNF-α production. This represents hitherto not described mechanisms for CG-associated inflammation.

ICs from SLE patients induced IL-10 and IL-6 production from PBMC cultures via FcγRIIa. Occurrence of anti-SSA autoantibodies and signs of in vivo complement activation contributed to increased levels of circulating ICs in SLE patients, corresponding to increased amounts of IC-induced IL-10 in vitro. This represents a possible vicious cycle that might perpetuate antibody dependent pathology in SLE, and put anti-SSA in a new pathological context.

RF-associated ICs from RA joints and ICs formed with antibodies against collagen type II from RA serum induced pro-inflammatory cytokine production from monocytes via FcγRIIa, showing how specific autoantibodies might induce or perpetuate joint inflammation in RA.

I have described how ICs can induce significant amounts of pathophysiologically important monocyte-derived cytokines in three major IC-dependent diseases. Blockade of FcγRIIa and suppression of monocytes/macrophages might be a means of reducing pathogenic IC-induced cytokine production in these diseases.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2007. 51 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 218
Immunology, Immune complex, Cytokines, Rheumatic diseases, Lymphoproliferative diseases, Immunologi
urn:nbn:se:uu:diva-7446 (URN)978-91-554-6780-6 (ISBN)
Public defence
2007-02-09, Rudbecksalen, Rudbecklaboratoriet, Dag Hammarskjöldsväg 20, Uppsala, 09:15
Available from: 2007-01-19 Created: 2007-01-19 Last updated: 2011-02-15Bibliographically approved

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