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P.179 ‘Epitope matching’, the must addition in pre-transplant algorithm

Dhanashree Shirish Rahalkar, India

Technlogist
Molecular Medicine
Reliance Life Sciences

Abstract

‘Epitope matching’, the must addition in pre-transplant algorithm

Dhanashree Rahalkar1,2, Karen Dwyer 1, Beata Ujvari1, Shailaja Saxena2, Arnab Kapat2, Shabari Sarang2.

1School of Medicine , Deakin University, Geelong, , Victoria, Australia; 2Molecular Medicine, Reliance Life Sciences, Navi Mumbai, India

Background: Chronic rejection is the leading cause of kidney graft failure. Underpinning transplantation immunology is the Human Leucocyte Antigen (HLA) complex. HLA mismatches are generally considered to give rise to the development of donor specific antibodies. However, not all mismatches ignite an immunogenic reaction and are deemed acceptable; whereas those that lead to donor specific antibodies are unacceptable. This phenomenon can be explained at the epitope level. This includes eplets that are known to elicit antibody production (antibody verified eplets), as well as eplets determined theoretically using modeling with crystalized HLA molecules (non-antibody verified eplets). Matching at epitope level may prove superior to conventional HLA matching and may be used as a tool for predicting allograft outcomes.
Objective:
1.To describe HLA A, B, DR haplotype distribution within states of Indian population.
2. To evaluate epitope mismatches in Indian transplant patients using HLA data and correlation with biopsy findings.
Methods: Data from transplant recipients referred for HLA typing and antibody profile at Molecular Medicine Laboratory of Reliance Life Sciences Pvt. Ltd. (RLS), Navi Mumbai and approved by Deakin University Ethics 2018-330 between years 2010 to 2019 were analyzed. 
HLA typing was performed by using PCR for donors and recipients. This data was subjected to Haplotype distribution using Arlequin software.
Allele level typing results were imputed into HLAMatchmaker computer algorithm (www.HLAMatchmaker.net) to calculate epitope mismatches. This data was correlated with biopsy findings.
Results:
1. The standard deviation for haplotype distribution within states of Indian population noted was very high indicating a high degree of polymorphism.
2. Eplet mismatched score was correlated well with biopsy analysis.  In C4d negative recipients’ class I eplet score for was lower than class l eplet score C4d positive cases. Higher class II eplet score contributes for negative outcomesand exhibit positve C4d expressions.
Conclusion: This study is the first to describe HLA allelic distribution and evaluate donor-recipient compatibility at the epitope level for pan-India population.Considerable HLA diversity was evident among the Indian population studied, which can pose challenges in the transplant context. Donor specific antibodies are not the sole determinant of transplant outcomes. Integration of  eplet analysis with existing protocols will prove novel tool for donor selection algorithms, This will help further in personalizing immunosuppression, which is associated with multiple collateral effects such as an increased risk of malignancy and a lower quality of life.

References:

[1] Eplet Mismatched Score, Epitope Matching, Graft Survival

Presentations by Dhanashree Shirish Rahalkar

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