PMID- 7558279 OWN - NLM STAT- MEDLINE DCOM- 19951030 LR - 20210526 IS - 0019-9567 (Print) IS - 1098-5522 (Electronic) IS - 0019-9567 (Linking) VI - 63 IP - 10 DP - 1995 Oct TI - Differential antibody isotype reactivity to specific antigens in human lymphatic filariasis: gp15/400 preferentially induces immunoglobulin E (IgE), IgG4, and IgG2. PG - 3772-9 AB - Lymphatic filarial infection in humans is associated with a strong skewing of the immune response towards the TH2 arm, with prominent interleukin 4-producing cells and elevated levels of immunoglobulin G4 (IgG4) and IgE antibodies in peripheral blood. To determine how such a generalized TH2 imbalance governs responses to individual parasite antigens, the profiles of isotypes of antibodies to two recombinant proteins of Brugia spp. were studied. One molecule was the C-terminal portion of the filarial heat shock protein 70 (Bpa-26), representative of a cytoplasmic protein, and the second antigen was a single unit of the tandem repeats of a Brugia polypeptide (BpL-4), a secreted product which is prominently exposed to the immune system. Serum samples from 146 individuals resident in areas in which brugian filariasis is endemic were used, and it was found that whereas the levels of IgG1 and IgG3 responses to both Bpa-26 and BpL-4 were high, IgG4 and IgE antibodies to only BpL-4, not to Bpa-26, were prominent. Thus, an antigen which is chronically exposed to the immune system elicited a TH2-dependent isotype switch, as manifested by increased IgG4 and IgE responses. Moreover, IgG4 and IgE responses to BpL-4 showed a strong negative association, suggesting that mediators other than interleukin 4 must be responsible for such differential regulation of these two isotypes. When the data were analyzed as a function of clinical status, a striking association between elevated levels of IgG3 antibodies to Bpa-26 and manifestation of chronic obstructive disease was found; elephantiasis patients showed significantly higher levels of IgG3 antibodies to Bpa-26 than microfilaremics and asymptomatic amicrofilaremics. This indicates that an imbalance of isotypes of antibodies to particular filarial antigens might play a role in the pathogenesis of chronic disease. FAU - Yazdanbakhsh, M AU - Yazdanbakhsh M AD - Department of Parasitology, University of Leiden, The Netherlands. FAU - Paxton, W A AU - Paxton WA FAU - Brandenburg, A AU - Brandenburg A FAU - Van Ree, R AU - Van Ree R FAU - Lens, M AU - Lens M FAU - Partono, F AU - Partono F FAU - Maizels, R M AU - Maizels RM FAU - Selkirk, M E AU - Selkirk ME LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Infect Immun JT - Infection and immunity JID - 0246127 RN - 0 (Antibodies, Helminth) RN - 0 (Antigens, Helminth) RN - 0 (Helminth Proteins) RN - 0 (Immunoglobulin G) RN - 0 (Immunoglobulin Isotypes) RN - 37341-29-0 (Immunoglobulin E) SB - IM MH - Adolescent MH - Adult MH - Aged MH - Animals MH - Antibodies, Helminth/*biosynthesis MH - Antigens, Helminth/*immunology MH - Brugia/*immunology MH - Elephantiasis, Filarial/*immunology MH - Female MH - Helminth Proteins/*immunology MH - Humans MH - Immunoglobulin E/biosynthesis MH - Immunoglobulin G/biosynthesis/classification MH - Immunoglobulin Isotypes/*biosynthesis MH - Male MH - Middle Aged MH - Th1 Cells/immunology MH - Th2 Cells/immunology PMC - PMC173530 EDAT- 1995/10/01 00:00 MHDA- 1995/10/01 00:01 PMCR- 1995/10/01 CRDT- 1995/10/01 00:00 PHST- 1995/10/01 00:00 [pubmed] PHST- 1995/10/01 00:01 [medline] PHST- 1995/10/01 00:00 [entrez] PHST- 1995/10/01 00:00 [pmc-release] AID - 10.1128/iai.63.10.3772-3779.1995 [doi] PST - ppublish SO - Infect Immun. 1995 Oct;63(10):3772-9. doi: 10.1128/iai.63.10.3772-3779.1995.