2016-10-13
Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD
Publication
Publication
Blood , Volume 128 - Issue 15 p. 1979- 1986
Graft-versus-host disease (GVHD) is among the most challenging complications in unrelated donor hematopoietic cell transplantation (HCT). The highly polymorphic MHC class I chain-related gene A, MICA, encodes a stress-induced glycoprotein expressed primarily on epithelia. MICA interacts with the invariant activating receptor NKG2D, expressed by cytotoxic lymphocytes, and is located in the MHC, next to HLA-B. Hence, MICA has the requisite attributes of a bona fide transplantation antigen. Using high-resolution sequence-based genotyping of MICA, we retrospectively analyzed the clinical effect of MICA mismatches in a multicenter cohort of 922 unrelated donor HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 10/10 allele-matched HCT pairs. Among the 922 pairs, 113 (12.3%) were mismatched in MICA. MICA mismatches were significantly associated with an increased incidence of grade III-IV acute GVHD (hazard ratio [HR], 1.83; 95% confidence interval [CI], 1.50-2.23; P < .001), chronic GVHD (HR, 1.50; 95% CI, 1.45-1.55; P < .001), and nonelapse mortality (HR, 1.35; 95% CI, 1.24-1.46; P < .001). The increased risk for GVHD was mirrored by a lower risk for relapse (HR, 0.50; 95% CI, 0.43-0.59; P < .001), indicating a possible graft-versus-leukemia effect. In conclusion, when possible, selecting a MICA-matched donor significantly influences key clinical outcomes of HCT in which a marked reduction of GVHD is paramount. The tight linkage disequilibrium between MICA and HLA-B renders identifying a MICA-matched donor readily feasible in clinical practice.
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| doi.org/10.1182/blood-2016-05-719070, hdl.handle.net/1765/96355 | |
| Blood | |
| Organisation | Erasmus MC: University Medical Center Rotterdam |
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Carapito, R. (Raphael), Jung, N. (Nicolas), Kwemou, M. (Marius), Untrau, M. (Meiggie), Michel, S. (Sandra), Pichot, A. (Angélique), … Bahram, S. (Seiamak). (2016). Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD. Blood, 128(15), 1979–1986. doi:10.1182/blood-2016-05-719070 |
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