Impact of HLA-C matching on acute graft-versus-host disease in allogenic hematopoietic hematopoietic stem cell transplantation

Abstract EN

Objective : Outcome of unrelated donor marrow transplantation is influenced by donor / recipient matching for HLA.

Prior studies assessing the effect of mismatch at specific HLA loci have yielded conflicting results.

Disparity for HLA-A or HLA-B antigens increases the risk of poor marrow graft outcome, but little is known about the relevance of HLA-C matching.

This work aimed to evaluate the effect of HLA-C matching on hematopoietic stem cell transplant outcome specifically on the acute graft versus host disease .(aGVHD) Methods : Seventy patients given hematopoietic stem cell transplant (HSCT) in different transplant centers with their relevant donors were included in the study.

HLA class I (HLA-A, -B) and class II (DRB1, DQB1, DPB1) typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probe (PCR-SSOP) and HLA-C typed by PCR-sequence specific priming (PCR-SSP) technique.

The risk of aGVHD during the first three months after HSCT was estimated.

Results : Fifty two (74.3 %) donor / recipient pairs were mismatched for HLA class I alleles, eighteen (34.6 %) of them experienced aGVHD.

While no history of aGVHD was reported in eighteen HLA class I full matched pairs (25.7 %).

Higher incidence of aGVHD was observed with isolated HLA-A mismatch (28.6 %), and for isolated HLA-B and HLA–C locus mismatch, the incidence were 25% and 16.7 % respectively.

The incidence of aGVHD was elevated if HLA-A or HLA–B mismatch is associated with HLA-C mismatch (40 % and 37.5 % respectively).

Much higher incidence of aGVHD was associated with combined HLA-A,–B and–C mismatch (44.4 %).

The estimated odds ratio (OR) of aGVHD for total HLA-C mismatch relative to matched pairs (invariable model) was 5.0 (95% CI, 1.3-19.4; P = 0.01).

The degree of HLA-C allele mismatch (one or two alleles mismatch) were significantly related to aGVHD outcome (OR, 3.9, P = 0.03; OR, 10.8; P = 0.009 respectively).

HLA-A or HLA-B allele disparity was also associated with aGVHD.

As regard the analysis of total HLA-A and –B mismatched pairs with their corresponding matched locus, they demonstrated significant adverse effect on aGVHD (OR, 2.8; P = 0.04 ; OR, 3.0; P = 0.03).

Conclusion : it was concluded that HLA-C may function as a powerful transplantation antigen.

HLA-C compatibility should be incorporated into algorithms for donor selection to improve the outcome especially in patients who have an increased risk.

The presence of HLA-C mismatch with either HLA-A or HLA-B mismatch leads to a synergistic increase in cytotoxic responses and poor graft outcomes (the development of aGVHD) ; however, isolated HLA-C mismatch may be acceptable with respect to T-cell mediated all reactivity.