Matching for the nonconventional MHC-I MICA gene significantly reduces the incidence of acute and chronic GVHD

Abstract

Key Points• Matching for MICA significantly reduces the incidence of acute and chronic GVHD in otherwise HLA 10/ 10-matched unrelated-donor HCT.• Our results formally define MICA as a novel major histocompatibility complex-encoded human transplantation antigen.

Matching for the MICA-129 polymorphism is beneficial in unrelated hematopoietic stem cell transplantation

“…10 Although Anderson et al have questioned this relationship, the recent report of Carapito et al conclusively confirmed this association. 33,34 We also saw higher rates of aGVHD in patients mismatched for MICA-129. However, Carapito et al also described a higher risk for cGVHD and a lower relapse rate in MICA mismatched cases, which we could not confirm for MICA-129 mismatched cases.…”

“…However, Carapito et al also described a higher risk for cGVHD and a lower relapse rate in MICA mismatched cases, which we could not confirm for MICA-129 mismatched cases. 34 We therefore speculate that an impaired NK-alloreactivity in the subgroup of MICA 1 MICA-129 mismatched cases, as opposed to MICA-mismatched 1 MICA-129 matched patients, may account for this difference. Carapito et al also analyzed matching for MICA-129 and saw no differences for all end points.…”

“…Carapito et al also analyzed matching for MICA-129 and saw no differences for all end points. 34 Given the low frequency of MICA-129 mismatched cases, the absence of a difference in this subanalysis may be a result of low case numbers or random sampling. In the 10/10 and 9/10 HLA-matched groups, Kaplan-Meier analysis indicated an increase in mortality around 6 months after transplant, which may correlate to late-onset aGVHD or progressive onset of cGVHD in MICA-129 mismatched cases, possibly requiring prolonged intensive immunosuppression treatment in these patients.…”

Which factors influence the development of GVHD in HLA-matched or mismatched transplants?

“…These results suggest that when HLA-A, B, C, DRB1 or DQB1-mismatched donors are available, additional testing of DRB3/4/5 may help to lower risks. Most recently, mismatching for the non-classical class I gene, MICA, has been shown to impact GVHD and survival in some [6,7], but not other, studies [8]. …”

Allogeneic transplantation of hematopoietic stem cells: Perspectives and alternatives, own experience

“…Кроме того, целесообразно учитывать уже известные минорные антигены, кото-рые также могут оказывать влияние на течение РТПХ. Так, в исследовании результатов алло-ТГСК (n = 922) от полностью (10/10) HLA-совместимых неродствен-ных доноров (R. Carapito et al, 2016) идентифициро-ван антиген MICA (MHC class I chain-related gene A), несовместимость по которому (n = 113) увеличивала риск острой (III-IV степени) и хронической РТПХ, а также смертности, не связанной с рецидивом, соот-ветственно в 1,83, 1,5 и 1,35 раза [97]. В то же время у пациентов с MICA-несовместимостью было отмече-но уменьшение риска рецидива при 6-летней медиане наблюдения (10,2 % против 18,3 %).…”