Body: A 31-year-old white male was diagnosed with MDS and evaluated for an allogeneic stem cell transplant. Upon comparing the HLA and MIC typing of the patient with his biological mother, (a potential donor), a complete mismatch at the MICA locus was observed. The recipient typed as homozygous MICA*008:04, while the mother typed as homozygous MICA*002:01 (Fig1). Sample mix-up was ruled out and we sought an alternate explanation. A literature review that revealed an association between HLA-B and MICA prompted us to further investigate the linkage of MICA and B alleles shared between the recipient and his mother, in this case, B*48:02. The highest prevalence of HLA-B*48:02 has been reported in individuals of Amerindians in South and Central America (allelefrequencies.net). A literature search revealed multiple reports of an association of MICA deletion with HLA-B*48:02. Additionally, a 100-kb deletion, which included the MICA gene, had been reported in the HLA-B48 (B*48:01) haplotype in the Japanese population (doi:10.1007/s002510050658). Ota et al., 2002 also found that MICA deletion was accompanied by a MICB null allele MICB*01:07N in their cohort of eight B48 homozygous individuals (doi:10.1034/j.1399-0039.2000.560309.x). A study by Aida et al. 2002 reported a high frequency of MIC null haplotype HLA-B48-MICA-delMICB*01:07N in Angaite Amerindian community in Paraguay (doi:10.1007/s00251-002-0485-1). We also observed a null MICB allele (MICB*09:01N) in both the recipient and his mother. A comprehensive analysis of our data, using the copy number tool (courtesy of CareDx), revealed a single copy of MICA in both samples evaluated, as indicated by the yellow bar in Fig 2, providing supporting evidence of a MICA del in this case, and consistent with previously published data on the HLA-B48-MICA-del association.
Conclusion: What appeared to be a MICA mismatch and maternal exclusion was instead attributable to a MICA hemizygous loss in the recipient and his mother. Two important points from this case should be considered: 1) while we have the ability to type for MIC A/B as part of the NGS AlloSeq Tx17 panel, such results are not currently reported, although this may change in the future. This case underscores that if such data are reported anomalous results must be questioned and further investigated and, 2) the appreciation of such findings may provide a tool for understanding the impact of such an evolutionary change.
