Donor-Specific Anti-HLA Antibodies and Endothelial C4d Deposition—Association With Chronic Liver Allograft Failure. Issue 9 (September 2015)

• Record Type: Journal Article
• Authors: Iacob, Speranta; Cicinnati, Vito R.; Lindemann, Monika; Heinemann, Falko M.; Radtke, Arnold; Kaiser, Gernot M.; Kabar, Iyad; Schmidt, Hartmut H. J.; Baba, Hideo A.; Beckebaum, Susanne
• Is Part Of: Transplantation. Volume 99:Issue 9(2015)
• Publication Date: 2015-09
• Subjects: Transplantation of organs, tissues, etc -- Periodicals; Transplantation immunology -- Periodicals; 617.95
• DOI: 10.1097/TP.0000000000000613
• Languages: English
• ISSNs: 0041-1337

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background</title> <p>The significance of humoral immune response for allograft survival after liver transplantation (LT) is still a matter of debate. The aim of this cross-sectional study was to assess immunological and clinical factors associated with advanced fibrosis (F3-F4) and chronic graft failure in LT recipients.</p> </sec> <sec> <title>Methods</title> <p>Serum samples from 174 patients prospectively enrolled and followed up for 12 months were tested for anti-HLA antibodies and compared against donor HLA types. Immunohistochemical C4d staining was performed on formalin-fixed, paraffin-embedded liver tissue.</p> </sec> <sec> <title>Results</title> <p>Mean time period from LT to enrollment was 66.9 ± 51.9 months. Independent predictive factors for graft failure included donor-positive cytomegalovirus serostatus (<italic>P</italic> = 0.02), donor-specific antibodies (DSA) against HLA class II (<italic>P</italic> = 0.03), donor age (<italic>P</italic> = 0.01), hepatitis C virus allograft reinfection (<italic>P</italic> = 0.0008), and biliary complications (<italic>P</italic> = 0.003). HLA class II DSA and HLA class I antibody positivity, hepatitis C virus reinfection, and mycophenolate mofetil-free regimens were significant risk factors for advanced fibrosis after LT. There was a significant association between C4d deposition on allograft endothelial cells and presence of class II DSA (<italic>P</italic> < 0.0001). Patients with C4d deposits had a 4.3 times higher risk of graft failure than those with negative staining and a significantly lower median time to graft failure (94.6 months [range, 3.6-158.9 months] vs 176.4 months [range, 9.4-217.8 months], <italic>P</italic> < 0.0001).</p> </sec> <sec> <title>Conclusions</title> <p>Screening for HLA DSA might be useful for early identification of LT recipients at increased risk of graft failure who could benefit from closer surveillance and tailored immunosuppressive regimens.</p> </sec> </abstract>