The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda).
Onchocerca volvulus infection usually results in a predominantly immunopermissive reaction called generalized onchocerciasis and characterized by high microfilarial burden and immunological tolerance to the worms. Rarely, however, infection leads to the sowda form of the disease displaying low microfilarial numbers, i.e. microfilarial control, and a T helper 2 (Th2)-type immune response including high immunoglobulin (Ig)E levels, and interleukin (IL)-13 being one of the key cytokines. The aim of this study was to investigate a possible association of a variant of the IL-13 gene, which confers an IgE-independent risk for asthma and atopy, with the immunologically hyper-reactive sowda form of onchocerciasis. Genotyping for the IL-13 variant Arg110Gln revealed a highly significant association of Arg110Gln with the sowda form (relative risk of 2.98, n = 19 patients), whereas the frequency of the variant was significantly lower in patients with generalized onchocerciasis (n = 92 individuals). Sowda patients had higher IgE levels than those with generalized onchocerciasis. Logistic regression analysis revealed that IgE and IL-13 are independent variables, each increasing the relative risk for sowda. Arg110Gln has been suggested to lead to enhanced IL-13 signaling and thus may be involved in shifting the immune reaction towards the hyper-reactivity characteristic for the sowda form, thereby promoting defense mechanisms.
Hoerauf
Achim
A
Bernhard Nocht Institute for Tropical Medicine, 20359 Hamburg, Germany. hoerauf@bni.uni-hamburg.de
Kruse
Susanne
S
Brattig
Norbert W
NW
Heinzmann
Andrea
A
Mueller-Myhsok
Bertram
B
Deichmann
Klaus A
KA
D000483:Alleles; D000818:Animals; D020022:Genetic Predisposition to Disease; D006801:Humans; D007073:Immunoglobulin E / Q000097:blood*; D018793:Interleukin-13 / Q000235:genetics* / Q000378:metabolism; D017181:Onchocerca volvulus / Q000276:immunology* / Q000472:pathogenicity; D009855:Onchocerciasis / Q000235:genetics* / Q000276:immunology / Q000469:parasitology; D011110:Polymorphism, Genetic; D012876:Skin Diseases, Parasitic / Q000235:genetics / Q000276:immunology / Q000469:parasitology
D018793:Interleukin-13; D007073:Immunoglobulin E