MICA paired with mismatches in other loci that may lead to increased risk of GVHD5 are also warranted.

The strength of the 2-locus linkage disequilibrium may differ in different HLA alleles and haplotypes; it is possible that some HLA-B alleles or haplotypes including specific HLA-B alleles show weaker linkage disequilibrium with MICA than others. We found that one or more of the alleles B*1801, B*3501, or B*3801 were present in 8 of 9 donor/recipient pairs matched in 10/10 alleles of HLA-A, B, C, DRB1 and DQB1 loci and presented one mismatch in MICA; in contrast, those HLA-B alleles were present in 28% (35 of 158) of the pairs fully matched in MICA and HLA-A/B/C/DRB1/DQB1 loci. The different distribution of HLA-B*1801, B*3501, and B*3801 in MICA matched and mismatched pairs was highly significant (P .001), suggesting that haplotypes or haplotype fragments bearing these alleles show higher grades of diversity, which, in turn, result in MICA mismatches in pairs otherwise matched in other HLA alleles. Anderson et al extended the analysis to a larger cohort of HLA 8/8 matched pairs (n 1676), in which MICA allele assignment was made putatively on the basis of the most common HLA-B/MICA associations, not on actual typing. D is a measurement of linkage disequilibrium. The tightest link has a value of 1.0, and a value close to 0 indicates random association. The D between HLA-B and MICA ranges in 0.87 to 0.95 in randomly selected persons with either African American or white ancestry.4 These values are lower than the estimations of D made by Anderson analyzing patients with a 12/12 allelematched donor. The predictions of MICA alleles in these patients may be less accurate than those made for patients matching in DQ and DP in addition to the 8/8 alleles. In addition, their analysis identified only statistically nonsignificant trends for the association of MICA polymorphisms and gastrointestinal GVHD. Similarly, our study failed to identify an association between presence of MICA*008 and outcomes. Therefore, the polymorphism in MICA molecules by themselves may play a small if any role in determining susceptibility/ resistance to acute GVHD and other outcomes in allogeneic hematopoietic stem cell transplantation. In summary, MICA mismatches are uncommon in 10/10 or 12/12 allele-matched pairs. However, our study indicates that MICA may be a transplantation locus, a finding that deserves evaluation in larger cohorts. Studies investigating mismatches in