HLA allele and haplotype polymorphisms among Croatian patients in an unrelated hematopoietic stem cell donor search program

• Investigation of HLA profile and matching among Croatian patients in unrelated HSCT
• No difference in frequency of HLA alleles among patients and controls was observed.
• 10/10 donors were found for 64.8% patients; most MMs were observed for HLA-DRB1 and -C.
• HLA-B*15:01, B*18:01, and B*51:01 are associated with MMs at the HLA-C locus.
• DRB1*11:04 might be also considered as a limiting factor in finding a 10/10 donor.

The aim of the present study was to investigate HLA alleles and haplotypes among Croatian patients in an unrelated HSCT program, and to analyze HLA matching in patient/donor pairs. Analysis was performed on a group of 105 patients and their donors, and 4000 unrelated donors from our registry (CBMDR) served as controls. PCR-SSO and PCR-SSP high-resolution methods for HLA-A, -B, -C, -DRB1, and -DQB1 loci were used for typing patient/donor pairs. Donors from CBMDR were tested for HLA-A, -B, and -DRB1 by PCR-SSO. No difference in frequency at HLA tested loci among patients and donors from CBMDR was observed. A fully matched donor (10/10) was found for 68 (64.8%) patients, and the highest number of mismatches was found for HLA-DRB1 and HLA-C alleles. The presence of HLA-B alleles (B*15:01, B*18:01, and B*51:01) associated with two or more HLA-C alleles as well as the presence of unusual HLA-B/HLA-C (B*35:01-C*07:01 and B*35:01-C*14:02) combinations resulted in mismatches at the HLA-C locus. Additionally, mismatches at the DRB1 locus were in most cases found for DRB1*11 alleles. The results suggest that the DRB1*11:04 allele might be considered as a limiting factor in finding a 10/10 matched donor. These data may help in the improvement of the searching protocol for unrelated donors for Croatian patients.