IgG2 containing IgM-IgG immune complexes predominate in normal human plasma, but not in plasma of patients with warm autoimmune haemolytic anaemia.

TLDR: The data presented here therefore extend the physiological function of IgG2, which is the protective immune response towards carbohydrate antigens in bacterial infections, and suggest IgG 2‐dependent regulation of immune responses to self‐immunoglobulin in humans.

Abstract: The different physicochemical and sterical properties of IgG subclasses may favour a selective enrichment of defined IgG subclasses in IgM-IgG immune complexes (IC) of human plasma under physiological conditions. Such enrichment of IgG subclasses in IgM-IgG IC of plasma may differ from the normal IgG subclass distribution in plasma itself, and contribute to the physiological functions of IgM-IgG IC. Systematic studies on the IgG subclass distribution in IgM-IgG IC in humans are lacking. Using specific analytical techniques to characterise IgM-IgG IC in human plasma (i.e. fast protein liquid chromatography, enzyme-linked immunosorbent assay, affinity biosensor technology), and taking warm autoimmune haemolytic anaemia (WAIHA) of humans as a disease model, we here demonstrate that: (i) IgG2 is the predominant IgG subclass in IgM-IgG IC under physiological conditions, (ii) the predominance of IgG2 within IgM-IgG IC may get lost in polyclonal IgG-mediated autoimmune disease and (iii) the IgG subclass distribution in IgM-IgG IC influences the interaction between IC and blood cells involved in antigen presentation. The data presented here therefore extend the physiological function of IgG2, which is the protective immune response towards carbohydrate antigens in bacterial infections, and suggest IgG2-dependent regulation of immune responses to self-immunoglobulin in humans. The disturbed IgG subclass distribution in IgM-IgG IC of patients with WAIHA might influence activity of self-reactive B cells involved in the pathophysiology of the disease.