Role of major histocompatibility complex variation in graft-versus-host disease after hematopoietic cell transplantation

Abstract

Graft-versus-host disease (GVHD) remains a significant potentially life-threatening complication of allogeneic hematopoietic cell transplantation (HCT). Since the discovery of the human leukocyte antigen (HLA) system over 50 years ago, significant advances have clarified the nature of HLA variation between transplant recipients and donors as a chief etiology of GVHD. New information on coding and non-coding gene variation and GVHD risk provides clinicians with options to consider selected mismatched donors when matched donors are not available. These advances have increased the availability of unrelated donors for patients in need of a transplant and have lowered the overall morbidity and mortality of HCT.

Genetic Diversity of HLA Class I and Class II Alleles in Thai Populations: Contribution to Genotype-Guided Therapeutics

“…Whereas HLA class II molecules gather exogenously synthesized peptide ligands by endocytic pathway and expressed with antigen-presenting cells (APCs), six main HLA class II genes including HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRA, and HLA-DRB1 (Ulvestad et al, 1994). The HLA system plays a critical role in regulating the immune response, tissue or organ transplantation, autoimmunity, vaccine development, susceptibility or resistance disease, and pharmacogenomics (Anania et al, 2017;Illing et al, 2017;Petersdorf, 2017). Over the past decade, there have been reported associations between various HLA alleles and different adverse drug reactions, especially severe cutaneous adverse reactions (SCARs).…”

Six novel HLA‐B, ‐DRB1, and ‐DQB1 alleles identified in Brazilian individuals

“…Since the discovery of the HLA system over 50 years ago, continuous improvements in the identification of new variants have been achieved for better outcome of allogeneic tissue grafting, including solid organ and hematopoietic stem cell transplantation . In the latter context, understanding of the nature of the HLA variation between recipients and donors has helped reducing the risk of graft‐vs‐host disease, thereby leading to lower transplant‐related mortality …”

“…3,4 In the latter context, understanding of the nature of the HLA variation between recipients and donors has helped reducing the risk of graftvs-host disease, thereby leading to lower transplant-related mortality. 5 The genomic DNA samples described here were extracted from the peripheral blood of six subjects from Minas Gerais state registered in the Brazilian Volunteer Bone Marrow Donors Registry. The HLA typing was performed by sequence-based typing (SBT) using SeCore HLA SBT kits (Invitrogen, Foster City, California).…”

Die Bedeutung von Polymorphismen in MICA und anderen Genen des NKG2D-Signalwegs für die hämatopoetische Stammzelltransplantation

“…Ein Teil dieser Risiken ist genetisch determiniert und kann verschiedenen Faktoren zugeschrieben werden [2]. So ist eine möglichst genaue Übereinstimmung der im Human-Leukocyte-Antigen-Komplex (HLA-Komplex) kodierten Haupthistokompatibilitätsantigene wichtig, um das Risiko einer akuten oder chronischen GvHD zu reduzieren [3]. Die HLA-Klasse-I-Moleküle HLA-A, HLA-B, HLA-C und die HLA-Klasse-II-Moleküle HLA-DR, HLA-DQ und HLA-DP spielen eine entscheidende Rolle bei der Immunantwort, weil sie Peptide binden und diese den CD8 + -bzw.…”

“…Dies ist nicht nur auf eine höhere genetische Ähnlichkeit von Geschwistern in Nicht-HLA-Genen zurückzuführen. Neben HLA-A, HLA-B, HLA-C, HLA-DRB1 und HLA-DQB1 spielen auch weitere im HLA-Komplex kodierte Gene eine Rolle [3]. So beeinflussen Unterschiede zwischen Spender und Empfänger in Mikrosatellitenmarkern [50] oder verschiedenen SNPs [51,52] in der HLA-Region, aber außerhalb der klassischen HLA-Loci, das Ergebnis einer HSCT.…”