P073 : IMMUNOBIOLOGY OF HLA-G IN SIBLING RELATED HEMATOPOIETIC STEM CELL TRANSPLANTATION

Abstract

Introduction The advancements in pre-transplant conditioning regimens and better immunosuppressive protocols have dramatically improved the outcome of hematopoietic stem cell transplantation (HSCT), however various complications faced by recipients include graft versus host disease (GvHD), conditioning related toxicity, and infections of which GvHD is the major cause of morbidity and mortality. Since GVHD is the most common cause of morbidity and mortality in HSCT recipients, identifying biomarkers for prediction of GVHD is important to improve transplant outcomes. Nonclassical human leukocyte antigen (HLA) class I molecule, HLA-G has been identified as a key mediator of tolerance. The 3’UTR, particularly the 14bp insertion/deletion polymorphism in exon 8, influences the HLA-G expression and soluble HLA-G levels and modulate the immune system to except the allograft. Aim The present study was performed to understand the clinical relevance of HLA-G in HSCT. Methods We evaluated 40 recipients who underwent HLA-identical sibling HSCT at our cenetr and 125 healthy controls. The 14bp polymorphism in the HLA-G exon 8-3’UTR and soluble HLA-G levels at different time points were evaluated. Of the 40 recipients, 37% patients manifested acute GVHD. Results We observed that in the healthy cohort ( N = 125), 50% were heterozygous del/ins followed by equal distribution of del/del and ins/ins (25% each). Genotype analysis of 14bp INDEL polymorphism, ins/ins 14bp allele was more frequent in the cohort that did not develop GVHD in comparison to those who develop GVHD (40% vs 11%). Further we observed sHLA-G levels were high (113 U/ μ l) in the group with ins/ins 14bp polymorphism in healthy. Next we observed that among the recipients that did not experience GvHD the sHLA-G levels gradually increased from 14 U/ μ l pre-transplant to 26 U/ μ l at day 30 and was as high as 38 U/ μ l at day 90. Whereas, in recipients who developed GvHD, the sHLA-G level decreased to 16 U/ μ l at day 30 and further decreases 10 U/ μ L at the time of GvHD. So this Indicate that increased sHLA-G levels may have influenced the inhibited manifestation of GvHD. Conclusion The leads indicate that increased sHLA-G levels may have influenced alloreactivity and the outcome of HSCT in our study cohort.