Pathogenicity and impact of HLA class I alleles in aplastic anemia patients of different ethnicities

Abstract

Acquired aplastic anemia (AA) is caused by autoreactive T-cell-mediated destruction of early hematopoietic cells. Somatic loss of human leukocyte antigen (HLA) Class I alleles was identified as a mechanism of immune escape in surviving hematopoietic cells of some AA patients. However, pathogenicity, structural characteristics and clinical impact of specific HLA alleles in AA remain poorly understood. Here, we evaluated somatic HLA loss in 505 AA patients from two multi-institutional cohorts.Using a combination of HLA mutation frequencies, peptide-binding structures, and association with AA in an independent cohort of 6,323 patients from the National Marrow Donor Program, we identified 19 AA risk alleles and 12 non-risk alleles and established a novel AA HLA pathogenicity stratification.Our results define pathogenicity for the majority of common HLA-A/B alleles across diverse populations. Our study demonstrates that HLA alleles confer different risks of developing AA, but once AA develops, specific alleles are not associated with response to immunosuppression or transplant outcomes. However, higher pathogenicity alleles, particularly HLA-B*14:02, are associated with higher rates of clonal evolution in adult AA patients. Our study provides novel insights into the immune pathogenesis of AA, opening the door to future autoantigen identification and improved understanding of clonal evolution in AA.

CD Markers and HLA Expression in Chronic Lymphocytic Leukemia Patients: correlations and clinical relevance

“…Within our cohort, we observed a statistically significant correlation between CD22 and the HLA-B*49:01:01, HLA-C*07:01:01, HLA-DPB1*02:01:02 and HLA-DRB1*07:01:01 alleles. Among these alleles, existing literature highlights associations between aplastic anemia and HLA-B*49:01:01 [56], acute myeloid leukemia and HLA-C*07 [57], childhood common acute lymphoblastic leukemia and HLA-DPB1*02:01 [58]. Regarding the involvement of HLA-DRB1*07:01:01 in the occurrence of CLL, the study conducted by Aung et al [59] concludes that HLA-DRB1*07 is more quickly involved in the occurrence of follicular lymphoma and does not increase the risk of CLL.…”

“…In our study group, we noted a statistically significant correlation between CD22 and HLA-B*49:01:01, HLA-DRB1*11:04:01, HLA-DRB1*15:02:01 and HLA-DPA1*01:03:01. While the literature lacks extensive documentation on the relationship between HLA-B*49:01:01 and CLL, as noted in the context of its association with CD22, this particular allele, appears to serve as a promising marker for aplastic anemia [56]. As for the role of HLA-DRB1*11:04:01 in disease occurrence, evidence suggests its implication in acute lymphoblastic leukemia (ALL) [82] and hairy cell leukemia, with hemolytic uremic [83].…”