106-P

• Published in: Human immunology Vol. 73; p. 117
• Main Authors: Zhang, Aiwen, Dunlap, Megan, Nowacki, Amy, Thomas, Dawn, Kawczak, Paul, McMichael, John, Sobecks, Roanld, Askar, Medhat
• Format: Journal Article
• Language: English
• Published: 01.10.2012
• Subjects: Allergy and Immunology
• ISSN: 0198-8859
• DOI: 10.1016/j.humimm.2012.07.232

Aim Natural killer (NK) cells are key players in immune surveillance against malignancies. Major histocompatibility complex (MHC) class I related chain A (MICA) is a cognate ligand for the activating receptor NKG2D expressed on the surface of NK, NKT, CD8+ and TCR γδ+ T cells. Allelic variants of MICA due to a single amino acid substitution at position 129 with a methionine (M) or valine (V) in the alpha2 domain have been reported to result in large differences in NKG2D binding, which may be related to acute and chronic GvHD. The utility of MICA-129 genotype as a genetic marker in association with clinical outcomes is linked to whether a sizable proportion of the population is represented in different genotypes. Methods We investigated the MICA 129 genotype distribution among two cohorts. Cohort I consisted of 388 bone marrow and solid organ donors (351 Cauc and 37 AF) as a random sample of the population. Cohort II consisted of 530 sequential BMT recipients (507 Cauc & 23 AF). The genotype distribution of both cohorts is shown in Tables 1 and 2. Results Our analysis indicated that at least 8% of cohorts analyzed represented the least frequent genotype (MM) and a racial difference in genotype distribution among Cauc and AF in cohort I (p-value <0.0001) and in cohort II (p-value = 0.06). We also observed a significantly different prevalence of MM genotype among bone marrow recipients (8%) and cohort I (20%) (p-value <0.0001). Conclusions These results indicate a sizable representation of MICA-129 genotypes in different populations which increases its clinical utility as a candidate biomarker. Observed differences among Cauc vs. AF and HSCT recipients vs. random population samples warrant further investigation on larger cohorts including other races.