Correlations of Donor Specific Antibodies and Acute Rejection with T Cell Subtype Infiltrates in Endomyocardial Biopsies
Renee Frank, Malek Kamoun, Priti Lal. Hospital of the University of Pennsylvania, Philadelphia, PA
Background: Acute antibody-mediated rejection (AMR) is a major complication after heart transplantation, posing a significant risk for allograft failure, cardiac allograft vasculopathy, and poor survival. While the inflammatory mileu of cellular rejection and Quilty lesions are well-known, the immunologic components AMR are not well understood. Our aim was to better define the immunophenotype of infiltrating lymphocytes in biopsies with AMR, specifically in relation to donor specific antibodies to HLA class I, II, or both.
Design: We performed a retrospective analysis of cardiac transplant patients with acute cellular rejection (ACR) who had concurrent endomyocardial biopsies (EMB), DSA measurements and immunofluorescence for C4d at our institution (2005-2011). DSA were evaluated against HLA class I and class II specificities pre and post transplant using flow cytometry and/or Luminex bead assays. ACR and AMR were based on the ISHLT 2005 report, including diffuse interstitial capillary C4d and DSA presence. Immunohistochemical analysis for CD3, CD4, CD8 and CD79a was performed using standard immunohistochemical protocols on one formalin-fixed paraffin embedded EMB from each patient. The number of lymphocytes expressing each protein was enumerated microscopically at 400X. Ratios of T:B cells and CD4:CD8 T cells were then calculated for each EMB.
Results: 76 cardiac transplant patients who had pre and post transplant DSA measurements were analyzed. Of these 76 patients, 37 had DSA against either HLA class I, class II, or both. Of patients with DSA, the average CD4:CD8 ratio in the EMB was 0.80 while those with only acute cellular rejection had a CD4:CD8 ratio of 1.49. Interestingly, the T:B cell ratio in patients with and without DSA was 5.7 and 5.5, respectively.
Conclusions: Cardiac transplant patients with AMR and ACR have more cytotoxic T cells than helper T cells in the EMB lymphocytic infiltrate compared with patients having only ACR. The biologic significance of this ratio is currently unknown but may aid in diagnosis and treatment of AMR. The T cell ratios did not differ by having DSA to class I, II, or both. The inflammatory infiltrate T:B cell ratio was similar in patients both with and without AMR.
Wednesday, March 6, 2013 9:30 AM
Poster Session V # 56, Wednesday Morning