DEVELOPMENT OF ALLERGY TO LABORATORY-ANIMALS IS ASSOCIATED WITH PARTICULAR GM AND HLA GENES

To find out whether IgG genes are involved in atopy we studied 26 of 1 01 laboratory technicians who had developed laboratory animal allergy (LAA). The genes for the constant region of the heavy chains of IgG su bclasses were analyzed by serum Gm allotypes, representing products on allelic level of the IGHCG1, IGHCG2 and 1GHCG3 on chromosome 14q32. T here was a significantly increased frequency of-the Gm(f,f;n,n;b,b) ge notype (57.7 instead of 22.3%, p<0.001) representing IgG1, IgG2 and Ig G3 molecules and in particular increased frequency of Gm genotypes wit h the homozygous expression of G2m (n,n) (69.2 instead of 27.4%, p<0.0 01) and of the Gm(f,n,b) haplotype (75 instead of 44.8%, p <0.001) com pared to a normal Caucasian population. An increased HLA-DR4 content o f the LAA group (61.5 instead of 33.7%, p<0.01) was further investigat ed for Gm allotypes. Among 16 HLA-DR4 LAA individuals, the Gm(f,f;n,n; b,b) genotype (56.3 instead of 22.3%, p<0.01) and the Gm genotypes wit h the homozygous expression G2m(n,n) (62.6 instead of 27.4%, p<0.01) d ominated. However, the HLA-DR4 frequency among Gm(f,f;n,n;b,b) of I,AA patients did not deviate from the frequency of healthy individuals of the same Gm genotype. The increased frequency of HLA-DR4 antigen in L AA patients might be due to its association to the Gm(f,f;n,n;b,b) gen otype. This study supports the following concept: the susceptibility o f developing LAA is associated with Gm allotypes Glm(f) expressed from IGHCGl, G2m(n) from IGHCG2 and G3m(b) from IGHCG3 on both alleles sit uated close to IGHCE on chromosome 14q32. The association of LAA to Gm allotypes [Gm(f,f;n,n;b,b)] expressed from chromosome 14q32 and of HL A class II antigens (HLA-DR4) expressed from chromosome 6P21.3 further confirms the polygenic inheritance of the immune response in atopy.