Abstract

The role of genetic factors predisposing to the occurrence of coeliac disease was supported by the demonstration of differences in the distribution of many genetic markers Ñ HLA system. The aim of the study was an attempt of genetic analysis of the existence of specific familial and allelic interrelationship in the secretion of certain class I HLA antigens (sHLA-I) in coeliac disease. The analysis included sHLA-I concentrations with reference to the associations between phenotype expression of certain HLA-I antigens (A1, B8) and disease manifestation. The study included: 425 serum samples obtained from children with coeliac disease (n=69), 319 serum samples obtained from their healthy siblings (n=49), 549 serum samples from probands' parents (n=91). Antigens HLA loci ABC were typed in a two-gradual microcytotoxic test according to NIH. Immunogenetic comparative analysis was related to the frequency of phenotypes and haplotypes in 1152 and 616 unrelated healthy persons, respectively. The following indices were determined: relative risk (RR) according to Svejgaard et al, etiologic fraction (EF, EFe) and preventive fraction (PF, PFE) according to Green. The level of sHLA-I determined in a semi-quantitative microabsorption test according to McLean et al. was compared with that obtained in 1515 sera of 248 persons forming control population. sHLA level for 13 antigens from locus A, 19 from locus B, 7 from locus C and markers of biallelic Bw4/Bw6 system was given as a sum of points of the inhibition of cytotoxic reaction. Positive associations  (p<0.0000...1) were observed for the following: HLA-A1, -B8,-Cw7, while negative associations were observed for HLA-A2. Haplotype HLA-A1-B8-Cw7 occurred significantly more frequently than in control group (p<0.000013Ð0.0000...1). There was a highly significantly lower
level of sHLA-ABC (p<0.0000...1) in sera of children with coeliac disease for: HLA-A1, A11, A32, B13, B27, B44, B51, Bw6, Cw1 and Cw3, while there was a significantly lower level of sHLA for sHLA-B38 (p<0.0052), B55 (p<0.0312) and Cw6 (p<0.0442). Significantly higher secretion was proved for sHLA-A23, Bw4 and Cw2. In the sera of siblings and parents, significantly lower differences of sHLA-I concentrations were observed in both cases for 3 antigens HLA-A (A11, A24, A32), 7 HLA-B (B13, B38, B39, B44, B51, B57, Bw6) and 3 HLA-C (Cw1, Cw3, Cw6). The detection of the presence of antigens HLA-A1, -B8 is a predisposing factor to the occurrence of hypersensitivity to gluten. Familial occurrence of decreased secretion of the same antigens may indicate the existence of common immunogenetic background for coeliac disease in this respect.

Keywords: soluble form of class I HLA antigens (sHLA-I), coeliac disease, HLA system, MHC