Sayer David, Nytes James, Jerkins James H, Anderson Matthew W
One Lambda | A ThermoFisher Company, Los Angeles, USA.
Diagnostic Laboratories and Blood Research Institute, Versiti, Milwaukee, WI, USA.
Hum Immunol. 2025 Jan;86(1):111186. doi: 10.1016/j.humimm.2024.111186. Epub 2024 Dec 5.
Donors for patients requiring hematopoietic cell transplant (HCT) are selected based on matching genetic sequences encoding the antigen recognition domain of specific HLA loci. However, differences in transplant outcomes in fully matched unrelated HCT compared with sibling HCT suggest that other genetic regions within the major histocompatibility complex (MHC) may contribute to HCT outcomes.
We sequenced the non-classical MHC loci (NCML) HLA-E, -F, -G, -H, MICA and MICB on a well-characterized retrospective cohort of 157 unrelated donor/recipient HCT pairs to determine the extent of MHC mismatching in matched pairs.
Mismatches were seen in one or more NCML in 131 of the 157 pairs (83 %), including 44 of 60 pairs (73 %) that were matched at 4th field resolution for HLA-A, HLA-C and HLA-B and 3rd field resolution for HLA-DRB1, HLA-DRB3,4,5, HLA-DQA1 and HLA-DQB1. Though not statistically significant, transplant outcome analysis suggested that highly HLA matched/NCML matched recipients had a greater risk of disease relapse and reduced likelihood of progression-free survival than recipients that were highly HLA matched/NCML mismatched.
NCML mismatching is present in HLA-matched unrelated HCT donor and recipient pairs and may contribute to outcomes in unrelated HLA-matched HCT.
对于需要进行造血细胞移植（HCT）的患者，供体是根据编码特定HLA基因座抗原识别域的基因序列匹配来选择的。然而，与同胞HCT相比，完全匹配的无关供体HCT移植结果存在差异，这表明主要组织相容性复合体（MHC）内的其他基因区域可能影响HCT结果。
我们对157对无关供体/受体HCT的特征明确的回顾性队列中的非经典MHC基因座（NCML）HLA-E、-F、-G、-H、MICA和MICB进行了测序，以确定匹配对中MHC不匹配的程度。
157对中的131对（83%）在一个或多个NCML中存在不匹配，包括60对中44对（73%）在HLA-A、HLA-C和HLA-B的第4场分辨率以及HLA-DRB1、HLA-DRB3、4、5、HLA-DQA1和HLA-DQB1的第3场分辨率上匹配。虽然无统计学意义，但移植结果分析表明，与高度HLA匹配/NCML不匹配的受者相比，高度HLA匹配/NCML匹配的受者疾病复发风险更高，无进展生存的可能性更低。
在HLA匹配的无关HCT供体和受体对中存在NCML不匹配，这可能影响无关HLA匹配的HCT结果。
