Humoral responses to a secretory Onchocerca volvulus protein: differences in the pattern of antibody isotypes to recombinant Ov20/OvS1 in generalized and hyperreactive onchocerciasis

Abstract

The Onchocerca volvulus secretory protein Ov20/OvS1 represents a dominant antigen expressed in the infective larvae, microfilariae and adult stages of the parasite. The humoral responses to this protein have not yet been analysed in the polar clinical and immunological forms of onchocerciasis. Analysis by ELISA of class and subclass antibodies to Ov20/OvS1 in persons with the generalized or the hyperreactive form of onchocerciasis revealed similar strong responses of IgG1, IgG4 and IgM antibody levels in both forms of onchocerciasis and significant differences were observed in the IgE and IgA antibody classes. Computation of the ratios of antibodies showed that persons with the generalized form exhibited significantly higher ratios of IgG4 to IgG1, IgG4 to IgE, and IgM to IgE than patients with the hyperreactive form. To investigate the isotype recognition of antigenic sites on Ov20/OvS1 protein, three recombinantly expressed fragments (F1-3) of Ov20/OvS1 were probed using sera which strongly reacted with intact recombinant Ov20/OvS1. Epitope(s) on F1 comprising amino acid residues 1-63 were significantly recognized by IgG1 and IgE, while IgM recognized epitopes on all three fragments. The strongest reaction of IgM occurred with epitope(s) formed by residues 108-171 (F3). In contrast, IgG4 type antibodies were not reactive with either of the three OvS1 fragments, but they reacted with intact Ov20/OvS1 protein. Generalized onchocerciasis, unable to eliminate microfilariae, and hyperreactive onchocerciasis, with a high potency to eliminate or to reduce parasite loads, can be distinguished by a distinct pattern of isotype responses to Ov20/OvS1.

Immunohistology of ectopic secondary lymph follicles in subcutaneous nodules from patients with hyperreactive onchocerciasis (sowda)

“…The predominance of B lymphocytes in the SLF corresponds to the strong antibody responses documented for the hyperreactive onchocerciasis (Brattig 2004; Brattig et al 1994; Büttner et al 1982; Gallin et al 1995; Mpagi et al 2000). The characteristic IgE network of FDCs expressing the low-affinity IgE (epsilon) receptor correlated well to the IgE presence in onchocercomas, lymph nodes and peripheral blood and represents a key feature of hyperreactive onchocerciasis (Racz et al 1983; Timmann et al 2003).…”

“…The characteristic IgE network of FDCs expressing the low-affinity IgE (epsilon) receptor correlated well to the IgE presence in onchocercomas, lymph nodes and peripheral blood and represents a key feature of hyperreactive onchocerciasis (Racz et al 1983; Timmann et al 2003). The IgE antibodies mainly refer to polyclonal IgE and in addition to Onchocerca protein-specific IgE (Mpagi et al 2000). No intracytoplasmatic expression of IgG subclasses was observed in the SLF although two subclasses are present in high concentrations in sera from hyperreactive patients (Brattig et al 1994).…”

Life Cycle Stage-resolved Proteomic Analysis of the Excretome/Secretome from Strongyloides ratti—Identification of Stage-specific Proteases

“…Sera from 10 rats taken before and 32 days after infection with S. ratti iL3 were analyzed by ELISA (27) for IgG antibodies reactive against S. ratti proteins in the E/S products from iL3, pF and flS. Polystyrene microtiter plates (Maxi-Sorb, Nunc) were coated with Strongyloides protein samples at a concentration of about 200 ng/well in carbonate buffer (pH 9.6), sealed with Saran wrap and incubated overnight at 4 °C.…”

Hyperreactive onchocerciasis exhibits reduced arachidonate and linoleate levels in serum triglycerides.

“…5 Prostaglandin E 2 , an eicosanoid produced or induced by filarial worms, 11 was reported to suppress the production of immunoglobulin E (IgE) antibodies 38 and type 1 T-helper cell (Th1) cytokines, particularly IL-2 and interferon gamma. 8,39 Interestingly, our previous observations showed significantly elevated total 24 and specific IgE antibodies 40 and elevated IL-2 41 levels in patients with hyperreactive onchocerciasis when compared to patients with the generalized form. Our earlier findings, mentioned previously, with profound implications on the host's antibody-dependent cytotoxicity mechanism, appear to support the hypothesis presented in this study that inadequate elaboration of eicosanoids by O. volvulus may prevent down-regulation of cellular and humoral responses to the parasite in persons with hyperreactive onchocerciasis.…”