Relevance of HLA Expression Variants in Stem Cell Transplantation

HLA‐B*38:55Q: a new alternatively expressed allele identified in a three‐generation Italian family

“…Matching donor and recipient for class I and II HLA antigens is crucial to the success of allogeneic hematopoietic stem cell transplantation (HSCT), as transplantation not perfectly matched will lead to the development of T‐cell responses to the mismatched HLA molecules, resulting in graft‐versus‐host disease (GvHD) or graft rejection in patients with insufficient immune suppression. Therefore, HLA null alleles or expression variants represent an increasingly debated topic as, if misdiagnosed as normally expressed variants, may result in HLA mismatches that are highly likely to stimulate allogeneic T cells and trigger GvHD (Eiz‐Vesper & Blasczyk, ). HLA class I molecules are stabilized by disulphide bonds located in the alpha‐2 and alpha‐3 domains between cysteine (C) residues at amino acid positions 101/164 and 203/259, respectively.…”

“…HLA null and expression variants are typically identified by the discrepancy between serological and molecular typing results, but molecular typing techniques have nearly displaced serological methods and many expression variants are likely to be overlooked (Eiz‐Vesper & Blasczyk, ). As in allogeneic HSCT expression variants can strongly impact transplant‐related mortality, increasing knowledge of the expression behaviour of HLA polymorphisms such as L and Q alleles will help to improve HLA allogenicity prediction algorithms.…”

A new non‐expressed allele HLA‐A*03:168N, identified by serological and sequence‐based typing in a voluntary Norwegian hematopoietic stem cell donor

“…In the setting of stem cell transplantation it is generally accepted that mismatches between human leukocyte antigen (HLA) null alleles and expressed variants should be avoided because of the strong likelihood of stimulating allogeneic T cell responses and triggering severe graft‐versus‐host disease (GVHD) or graft rejection . To date, the IMGT/HLA database (Release 3.13.1 July 2013) describes 113 null HLA‐A alleles, of which 12 belong to the group A*03 .…”