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Analysis of Human Leucocyte Antigen Class II Expression in Graft Liver Tissue; Donor Specific Antibodies and Graft Liver Fibrosis

Kaneshiro, Masakatsu1; Yoshizawa, Atsushi1; Ueda, Daisuke1; Yagi, Shintaro1; Hata, Koichiro1; Okajima, Hideaki1; Kaido, Toshimi1; Tsuruyama, Tatsuaki2; Uemoto, Shinji1

doi: 10.1097/

1Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan; 2Center for Anatomical Studies, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Introduction: We have previously reported the relationship between donor specific anti-HLA antibodies (DSA) and late liver graft fibrosis. Most of the DSA are against anti-HLA class II. The mechanisms for graft fibrosis have not been elucidated caused by DSA against HLA class II, which are generally expressed on antigen-presenting cells and B cells. We investigated HLA class II expression in graft liver tissue.

Methods: Twenty-one patients after liver transplantation for biliary atresia were involved in this study. The three patients received graft liver from ABO blood type incompatible donors. They had no complication which may cause liver fibrosis, such as surgical complications and late acute rejection. Their liver specimens were taken as a protocol liver biopsy after transplantation. Simultaneously, DSA in the sera were examined using Labscreen® Single Antigen by Luminex analyzer. Liver fibrosis was graded according to METAVIR scoring system. HLA class II expression was detected by immunohistochemical staining of HLA DR in paraffin-bedded specimens obtained by liver biopsy. The expression was separately evaluated in three areas; portal, centrilobular, and sinusoidal areas.

Results: In the DSA+ group, HLA class II expression in liver allograft was significantly higher than the DSA- group (p = 0.0085). In the DSA + fibrosis + group, HLA class II expression in the portal areas was significantly higher than that of the DSA + fibrosis- group (p = 0.042). On the other hand, In the DSA- group, there was no significant difference in expression of HLA DR in the portal area among the patients with and without liver fibrosis. The expression of HLA class II expression in the centrilobular area were significantly correlated with alanine transaminase level.

Conclusion: DSA and fibrosis positivity correlated with class II expression in graft liver tissue. Patients without fibrosis despite of existing DSA had less class II expression in portal area.

HLA-DR positive area

HLA-DR negative area





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