POSITIVE AND NEGATIVE ASSOCIATIONS OF MICA POLYMORPHISM WITH COELIAC DISEASE.
Naipal A.1, P. Hanifi Moghaddam1, J.B.A. Crusius 2, A.S. Peña 2, F. Koning 1, C.J.J. Mulder 3, F.H.J. Claas1, and I.I.N. Doxiadis1. 1 Department of Immuno-haematology and Blood Bank, Leiden University Medical Center, Leiden 2 Dept. of Gastroenterology, Free University Amsterdam, 3 Rijnstate Hospital, Arnhem, The Netherlands.
MICA, a stress induced non-classical MHC class I like gene, is expressed by epithelial and endothelial cells. It is a ligand for gamma/delta T cells in the gut. The numbers of gamma/delta T cells are elevated in intestinal biopsies of coeliac disease (CD) patients where they may recognize the stress induced MICA gene product. Since several MICA alleles exist we have questioned whether specific MICA alleles are involved in CD, in addition to the well accepted HLA-DQ2 and DQ8 association. We first established a microsatellite typing technique for the three nucleotide repeats in exon five of the MICA gene. Five alleles were observed named A4, A5, A5.1, A6, and A9. In the control population (N=98) the allele frequencies were as follows: 23.0, 0.1, 36.2, 31.6, and 8.2 % respectively. In a double blind manner we typed 41 patients with well defined CD. The respective frequencies were: 3.5, 5.8, 69.8, 16.3, 4.7 %. In this cohort of patients the allele A5.1 was significantly associated with CD (69.8 vs. 36.2 % in the controls) while the allele A4 seems to be protective (3.5 vs. 23.0 % in the controls). The present data open a possible new way in understanding CD. A5.1 encodes a glycoprotein with shortened transmembrane segment and no cytoplasmic tail, which probably is not expressed on the cell surface. It is variously linked to HLA-B7, B8, B13, B44, B47, and B60. The results indicate that CD patients preferably possess a particular MICA allele which suggest that a specific interaction between gamma/delta T cell and this MICA allele in the gut of patients could contribute to disease development. Alternatively, the reported MICA allele might be part of the CD associated MHC haplotype.