IgG4 antibodies from patients with asymptomatic bancroftian filariasis inhibit the binding of IgG1 and IgG2 to C1q in a Fc-Fc-dependent mechanism

Abstract

A striking feature of lymphatic filariasis (LF) is the clinical heterogeneity among exposed individuals. While endemic normals (EN) remain free of infection despite constant exposure to the infective larvae, a small group of patients, generally microfilaria free (Mf-) develops severe pathology (CP) such as lymphedema or hydrocele. Another group of infected individuals remains asymptomatic while expressing large amounts of microfilariae (Mf+). This Mf+ group is characterized by an immune-suppressed profile with high levels of anti-inflammatory cytokines and elevated IgG4. This particular immunoglobulin is unable to activate the complement. The complement system plays a critical role in both innate and adaptive immunity. However, its importance and regulation during LF is not fully understood. Using affinity chromatography and solid-phase-enzyme-immunoassays, we investigated the ability of antibody isotypes from LF clinical groups to bind C1q, the first element of the complement’s classical pathway. The results indicate that while C1q is similarly expressed in all LF clinical groups, IgG1–2 in the plasma from Mf+ individuals presented significantly lower affinity to C1q compared to EN, Mf−, and CP. In addition, selective depletion of IgG4 significantly enhanced the affinity of IgG1–2 to C1q in Mf+ individuals. Strikingly, no effect was seen on the ability of IgG3 to bind C1q in the same conditions. More interestingly, papain-generated IgG4-Fc-portions interacted with Fc portions of IgG1–2 as revealed by far-western blot analysis. These data suggest that while being unable to bind C1q, IgG4 inhibits the first steps of the complement classical pathway by IgG1 or IgG2 via Fc-Fc interactions.Electronic supplementary materialThe online version of this article (10.1007/s00436-019-06451-2) contains supplementary material, which is available to authorized users.

Antibody Subclass and Glycosylation Shift Following Effective TB Treatment

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Avidity in antibody effector functions and biotherapeutic drug design

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Adoptive Transfer of Immune Cells Into RAG2IL-2Rγ-Deficient Mice During Litomosoides sigmodontis Infection: A Novel Approach to Investigate Filarial-Specific Immune Responses

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