Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFalpha-dependent and Fc-receptor-independent way.

Jarius, S; Eichhorn, P; Albert, MH; Wagenpfeil, S; Wick, M; Belohradsky, BH; Hohlfeld, R; Jenne, DE; Voltz, R

doi:10.1182/blood-2005-12-019604

2007

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Title:: Intravenous immunoglobulins contain naturally occurring antibodies that mimic antineutrophil cytoplasmic antibodies and activate neutrophils in a TNFalpha-dependent and Fc-receptor-independent way.
Document type:: Evaluation Studies; In Vitro; Journal Article; Research Support, Non-U.S. Gov't
Author(s):: Jarius, S; Eichhorn, P; Albert, MH; Wagenpfeil, S; Wick, M; Belohradsky, BH; Hohlfeld, R; Jenne, DE; Voltz, R
Abstract:: Intravenous immunoglobulin (IVIg) preparations are increasingly used for therapy of several neuroimmunologic diseases. IVIg therapy is considered safe, although serious side effects like aseptic meningitis, cerebral vasospasm, or ischemic encephalopathy have been reported. These side effects are frequently associated with neutrophilic pleocytosis in the cerebrospinal fluid (CSF), suggesting a neutrophil-mediated mechanism. To elucidate the potential role of neutrophil activation, we analyzed IVIg preparations from 5 different commercial sources for the presence of antineutrophil cytoplasmic antibody (ANCA)-like immunoglobulins against ethanol-fixed peripheral-blood neutrophils, purified human antigens, and a panel of human and nonhuman tissues. All IVIg batches tested (n = 13) contained atypical ANCAs (IgG titer up to 1:2048, IgA up to 1:512). Moreover, all preparations were capable of inducing hydrogen peroxide production in TNFalpha-primed human neutrophils, with a significant correlation (P < .005) between atypical ANCA titers in IVIg preparations and neutrophil activation. Fc-mediated binding and activation was ruled out by the use of IVIg-F(ab')(2) fragments. Our findings strongly suggest that in vivo activation of TNFalpha-primed neutrophils by atypical ANCAs of IVIg may contribute to the side effects of IVIg therapy and for the first time demonstrate that the activation of neutrophil granulocytes by IVIg occurs in an Fc receptor (FcR)-independent, hence antigen-dependent, way.
Journal title abbreviation:: Blood
Year:: 2007
Journal volume:: 109
Journal issue:: 10
Pages contribution:: 4376-82
Language:: eng
Fulltext / DOI:: doi:10.1182/blood-2005-12-019604
Pubmed ID:: http://view.ncbi.nlm.nih.gov/pubmed/17264299
Print-ISSN:: 0006-4971
TUM Institution:: Institut für Medizinische Statistik und Epidemiologie
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mediaTUM Gesamtbestand Einrichtungen Schools TUM School of Medicine and Health Departments Clinical Medicine Institut für KI und Informatik in der Medizin (Prof. Rückert)2007