Heightened Measures of Immune Complex and Complement Function and Immune Complex–Mediated Granulocyte Activation in Human Lymphatic Filariasis

Abstract

The presence of circulating immune complexes (CICs) is a characteristic feature of human lymphatic filariasis. However, the role of CICs in modulating granulocyte function and complement functional activity in filarial infection is unknown. The levels of CICs in association with complement activation in clinically asymptomatic, filarial-infected patients (INF); filarial-infected patients with overt lymphatic pathologic changes (CPDT); and uninfected controls (EN) were examined. Significantly increased levels of CICs and enhanced functional efficiency of the classical and mannose-binding lectin pathways of the complement system was observed in INF compared with CPDT and EN. Polyethylene glycol–precipitated CICs from INF and CPDT induced significantly increased granulocyte activation compared with those from EN, determined by the increased production of neutrophil granular proteins and a variety of pro-inflammatory cytokines. Thus, CIC-mediated enhanced granulocyte activation and modulation of complement function are important features of filarial infection and disease.

Changes in Cytokine, Filarial Antigen, and DNA Levels Associated With Adverse Events Following Treatment of Lymphatic Filariasis

“…Other studies suggested that AEs may be related to circulating immune complexes (CICs) that form when filarial antigens are released by dying parasites [ 16 , 17 ]. CICs from plasma of LF-infected individuals have been shown to be proinflammatory when added to granulocytes [ 18 ]. A recent clinical trial provided us with the opportunity to use 21st-century methods to revisit the issue of AE pathogenesis.…”

Detection of drug specific circulating immune complexes from in vivo cynomolgus monkey serum samples

“…however, each of these assays uses some unique characteristic of immune complexes such as complement opsonization for quantification and their clinical significance is not well established (Van Hoeyveld and Bossuyt, 2000). Concentration of immune complexes in circulation of normal human individual ranges between 2.3 μg/mL (Senbagavalli et al, 2011) and 5 μg Eq/mL (Quidel, MicroVue, CIC-RAJI EIA, Cat # A002) depending on the method used. Therefore, IC may be present in circulation of normal individuals without causing disease, indicating steady state clearance of foreign or abnormal antigens.…”

Lymphatic Filariasis: Perspectives on Lymphatic Remodeling and Contractile Dysfunction in Filarial Disease Pathogenesis

“…Senbagavalli et al . have shown that high levels of circulating antigen, in combination with antigen‐specific antibodies, activate the complement system in asymptomatic persons, whereas the reduced status of complement activity in patients with chronic pathologic changes may aggravate disease morbidity . Studies in murine models suggest the involvement of both the Th1 and Th2 arms of immunity in resistance to filarial parasites .…”