Study of complement-mediated anaphylaxis in humans: The role of IgG subclasses (IgG1 and/or IgG4) in the complement-activating capacity of immune complexes

Luigi Bergamaschini, Teresa Santangelo, Alessio Faricciotti, Nicola Ciavarella, Pier Mannuccio Mannucci, Angelo Agostoni

Research output: Contribution to journalArticle

Abstract

The role of Ig classes and subclasses in complement activation has been investigated both in vitro and in experimental animals, but not in humans. This study was conducted to determine the immunologic events of post- transfusion anaphylaxis in humans, and the effects of immune complexes of different IgG subclass compositions on complement activation. The ability of immune complexes containing mixed IgG1 and IgG4 or IgG4 Ab only to activate complement was investigated in two patients with von Willebrand's disease (a congenital bleeding disorder). This disease was complicated by precipitating IgG alloantibodies to von Willebrand factor (vWF), which triggered complement-mediated anaphylaxis after infusion of vWF-containing preparations. Complement activation was greater in the presence of mixed IgG1- and IgG4-vWF complexes than with IgG4-vWF alone. In one patient, the generation of large amounts of C4a, C3a, and terminal complement complexes following the formation of mixed IgG1- and IgG4-vWF was associated with life- threatening anaphylaxis. In this patient, IgG4 appeared to have no inhibitory effect on antigen-bound IgG1-mediated complement activation. In the other patient, formation of IgG4-vWF led to a lesser degree of complement activation and was associated with moderately severe anaphylaxis. Since neither patient showed any biochemical alterations indicating the involvement of mast cells or the contact phase of coagulation at any time, it is probable that the pathogenetic mechanism of the clinical syndrome was a direct effect of complement anaphylatoxins on vascular permeability and smooth muscle contraction. In both patients, IgG-vWF bound C4 and C3 (IgG4-vWF to a lesser extent than mixed IgG1-and IgG4-vWF), and this probably prevented serum sickness as a complication.

Original languageEnglish
Pages (from-to)1256-1261
Number of pages6
JournalJournal of Immunology
Volume156
Issue number3
Publication statusPublished - Feb 1 1996

ASJC Scopus subject areas

  • Immunology

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