The variant Arg110Gln of human IL-13 is associated with an immunologically hyper-reactive form of onchocerciasis (sowda)

被引:47
作者
Hoerauf, A
Kruse, S
Brattig, NW
Heinzmann, A
Mueller-Myhsok, B
Deichmann, KA
机构
[1] Bernhard Nocht Inst Trop Med, D-20359 Hamburg, Germany
[2] Univ Freiburg, Childrens Hosp, Freiburg, Germany
关键词
onchocerciasis; sowda; helminths; IL-13; IgE; polymorphism; allelic variant;
D O I
10.1016/S1286-4579(01)01507-6
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Onchocerca volvidus 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. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.
引用
收藏
页码:37 / 42
页数:6
相关论文
共 36 条
[21]   Genetic variants of IL-13 signalling and human asthma and atopy [J].
Heinzmann, A ;
Mao, XQ ;
Akaiwa, M ;
Kreomer, RT ;
Gao, PS ;
Ohshima, K ;
Umeshita, R ;
Abe, Y ;
Braun, S ;
Yamashita, T ;
Roberts, MH ;
Sugimoto, R ;
Arima, K ;
Arinobu, Y ;
Yu, B ;
Kruse, S ;
Enomoto, T ;
Dake, Y ;
Kawai, M ;
Shimazu, S ;
Sasaki, S ;
Adra, CN ;
Kitaichi, M ;
Inoue, H ;
Yamauchi, K ;
Tomichi, N ;
Kurimoto, F ;
Hamasaki, N ;
Hopkin, JM ;
Izuhara, K ;
Shirakawa, T ;
Deichmann, KA .
HUMAN MOLECULAR GENETICS, 2000, 9 (04) :549-559
[22]   Onchocerciasis in a nonendemic population: Clinical and immunologic assessment before treatment and at the time of presumed cure [J].
Henry, NL ;
Law, M ;
Nutman, TB ;
Klion, AD .
JOURNAL OF INFECTIOUS DISEASES, 2001, 183 (03) :512-516
[23]   Endosymbiotic bacteria in worms as targets for a novel chemotherapy in filariasis [J].
Hoerauf, A ;
Volkmann, L ;
Hamelmann, C ;
Adjei, O ;
Autenrieth, IB ;
Fleischer, B ;
Büttner, DW .
LANCET, 2000, 355 (9211) :1242-1243
[24]  
Hogarth PJ, 1998, J IMMUNOL, V160, P5436
[25]   An IL13 coding region variant is associated with a high total serum IgE level and atopic dermatitis in the German Multicenter Atopy Study (MAS-90) [J].
Liu, X ;
Nickel, R ;
Beyer, K ;
Wahn, U ;
Ehrlich, E ;
Freidhoff, LR ;
Björkstén, B ;
Beaty, TH ;
Huang, SK .
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 2000, 106 (01) :167-170
[26]  
MANTEL N, 1959, J NATL CANCER I, V22, P719
[27]   A distinct role for interleukin-13 in Th2-cell-mediated immune responses [J].
McKenzie, GJ ;
Bancroft, A ;
Grencis, RK ;
McKenzie, ANJ .
CURRENT BIOLOGY, 1998, 8 (06) :339-342
[28]  
McMahon J. E., 1996, Manson's tropical diseases., P1321
[29]   HLA-D ALLELES ASSOCIATED WITH GENERALIZED DISEASE, LOCALIZED DISEASE, AND PUTATIVE IMMUNITY IN ONCHOCERCA-VOLVULUS INFECTION [J].
MEYER, CG ;
GALLIN, M ;
ERTTMANN, KD ;
BRATTIG, N ;
SCHNITTGER, L ;
GELHAUS, A ;
TANNICH, E ;
BEGOVICH, AB ;
ERLICH, HA ;
HORSTMANN, RD .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (16) :7515-7519
[30]  
Ott J., 1999, ANAL HUMAN GENETIC L