Sequence variation in NKG2D, MICA, and MICB affect risk of relapse post-HCT

Petersdorf EW, McKallor C, Malkki M, et al. Role of NKG2D Ligands and Receptor in Haploidentical Related Donor Hematopoietic Cell Transplantation. Blood Advances. 2023; (doi: 10.1182/bloodadvances.2022008922).

After haploidentical hematopoietic cell transplantation (HCT), sequence variation in the NKG2D receptor and its ligands, MICA and MICB, determines the likelihood of relapse. Working with a sample of 1,629 patients and their donors, researchers assessed for MICA residue 129 and the exon 5 short tandem repeat (STR); MICB residues 52, 57, 98, and 189; and for NKG2D residue 72. Favorable outcomes were observed with MICB-52Asp versus MICB-52Asn in patients, with MICA STR-mismatching versus matching in donors, and with NKG2D-72Thr versus NKG2D-72Ala in donors. Investigators discovered that transplant patients fared best when all three traits were present. Based on their findings, they propose that deliberately pairing patients with MICB-52Asp with donors characterized by MICA STR-mismatching and NKG2D-72Thr might increase the chances of survival after haploidentical HCT.

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