HLA class II donor specific antibodies are associated with graft cirrhosis after liver transplant independent of the mea

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RESEARCH ARTICLE

Open Access

HLA class II donor specific antibodies are associated with graft cirrhosis after liver transplant independent of the mean fluorescence intensity level Katharina Willuweit1* , Alexandra Frey1, Lisa Bieniek1, Andreas Heinold2, Matthias Büchter1,3, Peter A. Horn2, Heiner Wedemeyer1 and Kerstin Herzer1

Abstract Background: The importance of donor-specific antibodies (DSA) after liver transplantation (LT) for graft and patient survival is an ongoing controversy. So far it has not been elucidated when and in how far DSA are harmful for graft and patient survival. Therefore, we had the aim to investigate the association of DSA with complications after LT. Methods: Data of 430 LT recipients were collected and statistically analyzed. Detection of HLA antibodies (Ab) was performed by Luminex assay. Results: DSA were detected in 81 patients (18.8%). These were mainly HLA class II Ab (81.5%). HLA class II Ab show a higher MFI (median: 5.300) compared to HLA class I Ab (median: 2.300). There is no association between MFI levels and development of complications after LT. However, cirrhosis occurred significantly more often in DSA positive patients (18%) than in patients without detectable DSA (9%, P = 0.027). All DSA positive patients with cirrhosis of the graft showed HLA class II antibodies (OR: 3.028; 95% CI: 1.51–6.075; P = 0.002). Conclusion: Occurrence of HLA class II DSA after LT is associated with graft cirrhosis and may indicate a higher risk to develop graft damage independent on MFI and requires an individualized risk management. Keywords: Livertransplant, Donor specific antibodies, Complications, Liver cirrhosis, HLA-antibody

Background While DSA are established as risk factor for humoral rejections and lower graft and patient survival after kidney transplant, the role of DSA after LT and their contribution to graft failure and complications is still not clarified and debates remain controversial. Some studies suggested that DSA are harmful after LT and reported associations with acute antibody-mediated rejection (AMR), biliary strictures and long-term complications, * Correspondence: [email protected] 1 Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Hufelandstrasse 55, 45122 Essen, Germany Full list of author information is available at the end of the article

such as graft fibrosis and chronic rejection [1–3]. However, some of the observations may be explained by distinct circumstances and require validation in independent cohorts. We could recently show a higher prevalence of DSA in patients with autoimmune liver diseases (primary sclerosing cholangitis [PSC], primary biliary cirrhosis [PBC], and autoimmunhepatitis [AIH]) as underlying liver disease for LT. On the other hand distinct immunosuppressive drugs may influence the development of DSA as in out cohort an mTor inhibitor based immunosuppressive regimen reduced the risk to develop DSA [4].

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