Differential distribution of HLA-A, HLA-B, and HLA-DRB1 allele groups in Iranian pediatric and adult patients with acute lymphoblastic Leukemia: A Case-Control study

Farzad Ghandehari; Fatemeh Mirzaei; Seppo Meri; Reza Vojdani; Kurosh Kalantar

doi:10.1016/j.humimm.2026.111770

Differential distribution of HLA-A, HLA-B, and HLA-DRB1 allele groups in Iranian pediatric and adult patients with acute lymphoblastic Leukemia: A Case-Control study

Hum Immunol. 2026 Jun 4;87(8):111770. doi: 10.1016/j.humimm.2026.111770. Online ahead of print.

Authors

Farzad Ghandehari¹, Fatemeh Mirzaei², Seppo Meri³, Reza Vojdani⁴, Kurosh Kalantar⁵

Affiliations

¹ Hematology and Oncology Department, Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
² Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.
³ Department of Bacteriology & Immunology and the Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland.
⁴ Hematology and Oncology Department, Hematology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: kalantark@sums.ac.ir.
⁵ Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Bacteriology & Immunology and the Translational Immunology Research Program (TRIMM), University of Helsinki, Helsinki, Finland; Autoimmune Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran. Electronic address: vojdanir@sums.ac.ir.

PMID: 42242099
DOI: 10.1016/j.humimm.2026.111770

Abstract

Acute lymphoblastic leukemia (ALL) is the most common pediatric cancer. Biological differences between pediatric and adult ALL suggest that inherited immunogenetic factors, such as HLA polymorphisms, may influence susceptibility in an age-dependent manner. We evaluated associations between HLA-A, HLA-B, and HLA-DRB1 allele groups and ALL among pediatric and adult populations in Iran. This case-control study included 383 ALL patients and 379 age- and sex-matched healthy controls, stratified into pediatric (125 cases, 122 controls) and adult (258 cases, 257 controls) groups. HLA typing was performed by low-resolution SSP-PCR. In the pediatric cohort, HLA-A*11 was more frequent in controls than cases (15.16% vs 9.2%; p = 0.04), suggesting a possible protective association, while HLA-B*14 was increased in cases (5.6% vs 1.64%; p = 0.028), indicating potential susceptibility. In the adult cohort, HLA-A*26 (7.2% vs 3.49%; p = 0.008) and HLA-B*41 (4.67% vs 1.55%; p = 0.004) were more frequent in controls, indicating protective associations, whereas HLA-B*57 was more frequent in cases (2.33% vs 0.58%; p = 0.034), suggesting increased risk. In the pooled analysis, HLA-A*11 was more frequent in controls than cases (13.32% vs 9.79%; p = 0.031), suggesting a possible protective association. HLA-A*26 (7.12% vs 3.79%; p = 0.004) and HLA-B*55 (3.56% vs 1.44%; p = 0.008) were more frequent in controls, indicating protective associations. Conversely, HLA-A*24 (12.4% vs 16.84%; p = 0.014), HLA-B*57 (0.66% vs 1.96%; p = 0.026), were increased in cases, indicating risk allele groups. A*01-B*35-DRB1*11 haplotype was enriched in patients, while A*02-B*18-DRB1*11 and A*33-B*18-DRB1*11 were more frequent in controls.. Also, a statistically significant borderline association was detected for HLA-DRB1*13 (4.88% vs 7.31%; p = 0.048). In conclusion, this study identified distinct distribution patterns of HLA allele groups between Iranian pediatric and adult ALL patients.

Keywords: Acute lymphoblastic leukemia; HLA-A; HLA-B; and HLA-DRB1.