Influence of Preformed Antibodies in Liver Transplantation.

Isabel Legaz,Alfredo Minguela,Francisco Sánchez-Bueno,Manuela López,Santiago Llorente,Francisco Boix,Rafael Alfaro,Pablo Ramírez,Jose A Campillo,María R Moya-Quiles,José A Galián,José A Pons,Manuel Muro,Carmen Botella

doi:10.3390/jcm9030708

Abstract

The significance of human leukocyte antigen (HLA) matching and preformed donor-specific antibodies (DSAs) in liver transplantation remains unclear. The aim of this study was to analyze the presence of DSAs in a large cohort of 810 liver recipients undergoing liver transplant to determine the influence on acute (AR) or chronic liver rejection (CR), graft loss and allograft survival. DSAs were identified using complement dependent cytotoxicity crossmatch (CDC-CM) and multiplexed solid-phase-based flow cytometry assay (Luminex). CDC-CM showed that a 3.2% of liver transplants were positive (+CDC-CM) with an AR frequency of 19.2% which was not different from that observed in negative patients (−CDC-CM, 22.3%). Only two patients transplanted with +CDC-CM (7.6%) developed CR and suffered re-transplant. +CDC-CM patients showed a significantly lower survival rate compared to −CDC-CM patients (23.1% vs. 59.1%, p = 0.0003), developing allograft failure within the first three months (p < 0.00001). In conclusion, we have demonstrated a relationship between the presence of preformed DSAs and the low graft liver survival, indicating the important role and the potential interest of performing this analysis before liver transplantation. Our results could help to detect patients with an increased risk of graft loss, a better choice of liver receptors as well as the establishment of individualized immunosuppressive regimens.

Highlights

Acute humoral rejection in organ transplantation is generally a result of the presence, in the recipient, of preformed antibodies against donors human leukocyte antigens (HLA), referred to as donor-specific antibodies (DSAs) [1]
Out of 810 liver recipients, Acute rejection (AR) was reported in 27.4% patients, with a 78.8% of episodes occurring within the first month after transplantation
Before the end of the first post-transplant year, most liver recipients with +Complement dependent cytotoxicity crossmatch (CDC-CM) suffered from allograft failure with an allograft loss rate of 69.2%. Because this highest incidence of graft failure shown within the first year post-transplantation, we further investigated the potential effect of the presence of preformed DSA as risk factor for graft loss during the first 12 months post-transplant

Summary

Introduction

Acute humoral rejection in organ transplantation is generally a result of the presence, in the recipient, of preformed antibodies against donors human leukocyte antigens (HLA), referred to as donor-specific antibodies (DSAs) [1]. The association between progressive fibrosis and the presence of DSAs in paediatric and adult liver-transplant recipients [10,11], the impact of DSAs in short- and long-term liver transplant outcome remains poorly understood [12,13,14,15,16]. Increasing evidence suggests that DSA are associated with both acute and chronic liver allograft rejection [17,18,19]. For these reasons, it seems prudent to re-examine the impact of DSA on liver allograft structure and function, including short- and long-term liver transplant outcome. Recent studies have reported several genetic markers and soluble molecules as potential surrogate biomarkers for the outcome of liver transplantation [20,21,22,23] and allosensitization could be important for an improvement in liver transplant outcome [24]

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