[HLA-DRB1/DQA1/DQB1 alleles and haplotypes in Czech children with celiac sprue]

The celiac disease (CD) is a multifactor disease resulting from a life time abnormal immune response to gluten accompanied by autoimmune characteristics, which can in sensitive individuals evoke small bowel mucosa morphologic changes. The genetically sensitive individual to CD has not been defined yet, it is obvious, however, that this illness is closely linked to the HLA class II genes. The objective of our study was to detect associations of HLA class II alleles and haplotypes DRB1/DQA1/DQB1 in Czech CD children.

A group of Czech CD children diagnosed according to ESPGHAN criteria was genotyped HLA for alleles of DRB1/DQA1/DQB1 loci. Genotyping of the HLA-DRB1/DQB1 haplotypes proved statistically significant association CD with haplotypes and alleles of this genetic system. 92.9% of patients have in their HLA phenotype allele DQA1*0501 in either cis or trans configuration with the DQB1 allele *0201/*0202. The extended HLA haplotype DRB*0301/DQA1*0501/DRB1*0201 as well as the haplotype DRB1*0701/DQA1*0201/DQB1*0202, are presented in 63.6% or in 61.0% CD patients respectively. The individual HLA class II alleles DRB*0301, *0701, DQA1*0201, *0501, DQB1*0201, *0202 and the above mentioned HLA haplotypes inclusively provide genotypic frequencies significantly different from healthy Czech individuals (P < or = 0.06 +/- 0.001). These results support the opinion that the HLA molecule expressed on the cellular surface as a alpha beta heterodimer encoded by the DQA1*0501 and DQB1*0201/02 alleles in either cis or trans configuration is responsible for the primary sensitivity to this disease. We were, however, not able to find an association of various clinical forms of the CD with a certain HLA haplotype in the followed group.

The CD patients have in comparison with healthy population significantly different frequency of HLA class II haplotypes. Though the finding of these alleles is not sufficient for an explicit confirmation of this diagnosis, the proof of this risky haplotype/s may notably contribute to it, namely in case of potential or latent forms of this disease.