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Cryoglobulin-induced cytokine production via FcgammaRIIa: inverse effects of complement blockade on the production of TNF-alpha and IL-10. Implications for the growth of malignant B-cell clones.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Immunology. Klinisk immunologi. (Autoimmunitet)
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Immunology. Klinisk immunologi. (Autoimmunitet)
Department of Medical Sciences. Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Immunology.
Department of Medical Sciences. Teknisk-naturvetenskapliga vetenskapsområdet, Faculty of Science and Technology, Biology, Department of Cell and Molecular Biology, Molecular Immunology.
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2005 (English)In: British Journal of Haematology, Vol. 129, no 6, 830-838 p.Article in journal (Refereed) Published
Abstract [en]

Monoclonal antibodies produced by patients with lymphoproliferative diseases sometimes appear as cryoglobulins (CG), immunoglobulins (Ig) that reversibly agglutinate and form immune complexes (IC) when cooled below normal body temperature or through variation in pH and ionic strength. In accordance with our findings of IC-induced cytokine production from peripheral blood mononuclear cells (PBMC) in systemic lupus erythematosus, we investigated whether CG can also induce cytokine production. One IgG and one IgM type I CG from two patients with multiple myeloma and Waldenstrom's macroglobulinaemia were individually purified and added to PBMC cultures. In separate experiments temperature and ionic strength were varied, or FcgammaRIIa, FcgammaRIII and complement activation were blocked; supernatant cytokine levels were then determined by enzyme-linked immunosorbent assay. CG-induced cytokine production from monocytes varied with precipitation induced by changes in temperature and ionic strength and was mediated via FcRIIa- and complement-dependent mechanisms. Complement blockade resulted in increased IgG CG-induced interleukin (IL)-10 production that was inversely correlated with decreased production of tumour necrosis factor-alpha. CG-induced IL-10 might be a growth factor for malignant B-lymphocytes in CG-associated lymphoproliferative diseases with constant complement consumption. Knowledge of mechanisms underlying CG-induced cytokine production can be useful for designing treatments for type I CG-associated pathology in lymphoproliferative diseases.

Place, publisher, year, edition, pages
2005. Vol. 129, no 6, 830-838 p.
Keyword [en]
cryoglobulinemia, Fcgamma receptors, cytokines, immune complex, complement, Aged, Antigens; CD/*immunology, B-Lymphocytes/*immunology/pathology, Cells; Cultured, Complement Inactivator Proteins/immunology, Complement Pathway; Classical/immunology, Cryoglobulinemia/*immunology/pathology, Cryoglobulins/*immunology, Cytokines/*biosynthesis, Female, Humans, Hydrogen-Ion Concentration, Immunoglobulin G/immunology, Immunoglobulin M/immunology, Interleukin-10/biosynthesis, Male, Middle Aged, Monocytes/immunology, Receptors; IgG/*immunology, Temperature, Tumor Necrosis Factor-alpha/biosynthesis, Tumor Stem Cells/pathology
Identifiers
URN: urn:nbn:se:uu:diva-74656DOI: doi:10.1111/jOAI: oai:DiVA.org:uu-74656DiVA: diva2:102566
Available from: 2008-01-28 Created: 2008-01-28 Last updated: 2011-01-11

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Mathsson, LindaNilsson, BoRönnelid, Johan

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