In:
Nature Medicine, Springer Science and Business Media LLC, Vol. 28, No. 5 ( 2022-05), p. 989-998
Abstract:
The identity of histocompatibility loci, besides human leukocyte antigen ( HLA ), remains elusive. The major histocompatibility complex (MHC) class I MICA gene is a candidate histocompatibility locus. Here, we investigate its role in a French multicenter cohort of 1,356 kidney transplants. MICA mismatches were associated with decreased graft survival (hazard ratio (HR), 2.12; 95% confidence interval (CI): 1.45–3.11; P 〈 0.001). Both before and after transplantation anti-MICA donor-specific antibodies (DSA) were strongly associated with increased antibody-mediated rejection (ABMR) (HR, 3.79; 95% CI: 1.94–7.39; P 〈 0.001; HR, 9.92; 95% CI: 7.43–13.20; P 〈 0.001, respectively). This effect was synergetic with that of anti-HLA DSA before and after transplantation (HR, 25.68; 95% CI: 3.31–199.41; P = 0.002; HR, 82.67; 95% CI: 33.67–202.97; P 〈 0.001, respectively). De novo-developed anti-MICA DSA were the most harmful because they were also associated with reduced graft survival (HR, 1.29; 95% CI: 1.05–1.58; P = 0.014). Finally, the damaging effect of anti-MICA DSA on graft survival was confirmed in an independent cohort of 168 patients with ABMR (HR, 1.71; 95% CI: 1.02–2.86; P = 0.041). In conclusion, assessment of MICA matching and immunization for the identification of patients at high risk for transplant rejection and loss is warranted.
Type of Medium:
Online Resource
ISSN:
1078-8956
,
1546-170X
DOI:
10.1038/s41591-022-01725-2
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2022
detail.hit.zdb_id:
1484517-9
Bookmarklink