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Expression of sHLA-G Identifies Favorable Outcome in Renal Transplant Recipients

Tyagi, Shweta1; Kanga, Uma1; Agarwal, Sanjay2; Bansal, V.K.3; Maurya, Manish1

doi: 10.1097/01.tp.0000520334.92669.aa
118.6
Free

1Department of transplant Immunology and Immunogenetics, All India Institute of Medical Sciences, New Delhi, India; 2Department of Nephrology, All India Institute of Medical Sciences, New Delhi, India; 3Department of Surgical Operations, All India Institute of Medical Sciences, New Delhi, India.

All India Institute of Medical Sciences, New Delhi. Indian Council of Medical Research, India.

Introduction: HLA-G is a non-classical HLA molecule and better known to play a crucial role in allogenic situations such as pregnancy or allograft transplantation. The higher expression of this molecule is related with better outcome in allograft transplantation.

Objective: The aim of the study was to investigate the role of HLA-G in North Indian patients undergoing renal transplantation.

Materials and Methods: A total of 39 recipient-donor pairs were enrolled in the study (Department of Nephrology/Surgery) and results were compared with 50 healthy controls. Of the 39 recipient-donor pairs enrolled, 11 subjects experienced graft rejection episodes. HLA-G exon 8- 14 bp INDEL polymorphism was tested by PCR-SSP and sequencing. Serum soluble HLA-G levels (pre-transplant, day 15, 30, 60, and 90) were measured using ELISA.

Results: The distribution of HLA-G 14 bp genotype among the healthy controls was exon 8-14 bp ins/del-46%, del/del-24% and ins/ins-30%. Among the recipients, the genotype data was evaluated on segregation of recipients in rejection and non-rejection groups. In non-rejection group, higher percentage of recipients carried ins/ins genotype as compared to the rejection group (32.1% vs 20% respectively). 60% of recipients in rejection and 46.4% of recipients in non-rejection group carried the heterozygous genotype. Distribution of del/del genotype was similar in both groups. The median sHLA-G level was 31.7 U/ml in healthy controls. sHLA-G levels were higher in the individuals with ins/ins genotype in comparison to del/del or ins/del genotype. It was observed that the sHLA-G levels were significantly high in renal transplant recipients when compared with healthy controls. sHLA-G levels were lower in the recipient cohort which experienced a rejection episode (median-105.4 U/ml) as compared to recipients maintaining well-functioning grafts (median- 260.4 U/ml). In the group with well-functioning graft, the sHLA-G levels were better maintained throughout the post-transplant period, whereas in the rejection group, the sHLA-G levels improved only after anti-rejection therapy, however, the levels were lower than well-functioning group.

Discussion: It is evident that HLA-G 3’UTR genotyping and serial monitoring of sHLA-G levels in serum/plasma may be useful tests for predicting any adverse event like rejection.

All India Institute of Medical Sciences, New Delhi. Indian Council of Medical Research, India.

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