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MICA-A5.1 weighs in with HLA-DR3/DQ2 in coeliac disease

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People with atypical forms of coeliac disease (CD) have another gene which may influence their disease as well as the already recognised MHC DR3/DQ2 allele. MHC class I chain related gene A (MICA), which specifies an enterocyte protein recognised by T cells and exists in strong linkage disequilibrium with HLA-B, is involved in atypical CD.

Among 133 patients with CD the frequencies of the heterodimer DQA1*0501/DQB1*0201 were similar in patients with typical or atypical CD and much higher than in the controls, as expected. Patients with atypical CD, however, had a significantly greater frequency of the extended haplotype E8.1 (B8/DR3/DQ2) (odds ratio 4.19; 95% confidence interval 1.97 to 8.84) than those with typical CD or the controls, and also of polymorphism MICA-A5.1 (odds ratio 8.63; 3.11 to 23.94).

This relation could not be explained by the linkage disequilibrium known to exist between MICA-A5.1 and extended haplotype E8.1. Although all patients and controls with the extended haplotype E8.1 also had the MICA-A5.1 allele, patients without this haplotype had a significant overrepresentation of the MICA-A5 allele if they had atypical CD (64% (9/14) v 22% (10/47), odds ratio 6.66; 1.82 to 24.36).

The study included 133 consecutive Spanish patients with CD presenting to two hospitals, 79 with typical and 54 with atypical CD according to clinical symptoms, and 116 healthy unrelated controls from the general population. Each was typed for HLA-DRB1, DQA1, DQB1 and exon 5 of the MICA gene by polymerase chain reaction sequence specific primers.