Role of major histocompatibility complex class I-related molecules A*A5 center dot 1 allele in ulcerative colitis in Chinese patients

Abstract

P>The major histocompatibility complex (MHC) class I-related molecules A (MICA) is a stress-inducible cell surface antigen that is recognized by intestinal epithelial V delta 1 gamma delta T cells, natural killer (NK) cells and CD8(+) T cells with NKG2D receptor participating in the immunological reaction in the intestinal mucosa. The present study aimed to investigate the functions of the MICA*A5.1 allele in the development of ulcerative colitis (UC) in the Chinese population. The microsatellite polymorphisms of MICA were genotyped in 124 unrelated Chinese patients with UC and 172 ethnically matched healthy controls using a semiautomatic fluorescently labelled polymerase chain reaction. MICA*A5.1-expressing Raji cells were generated by gene transfection. Cytotoxicity of NK cells to Raji cells expressing different MICA molecules was detected using the lactate dehydrogenase method. Soluble MICA in the culture supernatant was detected by enzyme-linked immunosorbent assay. The frequency of MICA*A5.1 was significantly higher in UC patients compared with the healthy controls (29 center dot 0% versus 17 center dot 4%, P = 0 center dot 001, corrected P = 0 center dot 005, OR = 1 center dot 936, 95% CI 1 center dot 310-2 center dot 863) and the frequency of a MICA*A5.1/A5.1 homozygous genotype was increased in UC patients (18 center dot 5% versus 7% in healthy controls, P = 0 center dot 0032, corrected P = 0 center dot 048, OR = 3 center dot 036, 95% CI 1 center dot 447-6 center dot 372). Raji cells with MICA*A5.1 expression produced more soluble MICA (t = 5 center dot 75, P < 0 center dot 01) than Raji cells with full-length MICA expression in culture supernatant. Raji cells with MICA*A5.1 expression were more resistant to killing by NK cells than Raji cells with full-length MICA expression. The MICA*A5.1 allele and MICA*A5.1/A5.1 genotype are significantly associated with Chinese UC patients in central China. MICA*A5.1 may play a role in the development of UC by producing more soluble MICA and resistance to NK cells.