PMID- 25440957 OWN - NLM STAT- MEDLINE DCOM- 20160316 LR - 20150513 IS - 1879-1336 (Electronic) IS - 1054-8807 (Linking) VI - 24 IP - 3 DP - 2015 May-Jun TI - Correlations of lymphocyte subset infiltrates with donor-specific antibodies and acute antibody-mediated rejection in endomyocardial biopsies. PG - 168-72 LID - S1054-8807(14)00143-4 [pii] LID - 10.1016/j.carpath.2014.11.001 [doi] AB - 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 milieu of cellular rejection and Quilty lesions is well known, the immunologic components of 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 human leukocyte antigen (HLA) class I, II, or both. METHOD: We performed a retrospective analysis of cardiac transplant patients with concurrent endomyocardial biopsies (EMB), donor-specific antibody (DSA) measurements, and immunofluorescence for C4d at our institution (2005-2011). DSA was evaluated against HLA class I and class II specificities pre- and posttransplant using flow cytometry and/or Luminex bead assays. Acute cellular rejection (ACR) and pathologic AMR (pAMR) were based on the International Society for Heart and Lung Transplantation 2005/2013 reports. 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: Seventy-nine cardiac transplant patients who had pre- and posttransplant DSA measurements were analyzed. Of these 79 patients, 37 had DSA against HLA class I, HLA class II, or both. Of patients with DSA, the average CD4:CD8 ratio in the EMB was 0.80, while those with only ACR 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. CONCLUSION: Cardiac transplant patients with DSA against HLA have more CD8 cytotoxic T cells than CD4 helper T cells in the EMB lymphocytic infiltrate compared with patients without DSA against HLA. The inflammatory infiltrate T:B cell ratio was similar in patients both with and without DSA. The relative increase of cytotoxic T cells in EMB while the patient has DSA suggests a possible pathogenic role of these cells and may aid in the diagnosis and treatment of AMR. CI - Copyright (c) 2014 Elsevier Inc. All rights reserved. FAU - Frank, Renee AU - Frank R AD - Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, United States. Electronic address: renee.s.frank@gmail.com. FAU - Dean, Stephanie A AU - Dean SA AD - Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, United States. FAU - Molina, Maria R AU - Molina MR AD - Heart Failure and Cardiac Transplant Program, Division of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, United States. FAU - Kamoun, Malek AU - Kamoun M AD - Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, United States. FAU - Lal, Priti AU - Lal P AD - Pathology and Laboratory Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, United States. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20141107 PL - United States TA - Cardiovasc Pathol JT - Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology JID - 9212060 RN - 0 (Antibodies) SB - IM MH - Adult MH - Aged MH - Allografts/immunology MH - Antibodies/*immunology MH - Biopsy MH - CD4-Positive T-Lymphocytes/*immunology MH - CD8-Positive T-Lymphocytes/*immunology MH - Female MH - Flow Cytometry MH - Graft Rejection/*immunology/pathology MH - Heart Transplantation/adverse effects MH - Humans MH - Immunohistochemistry MH - Immunophenotyping MH - Lymphocyte Subsets/immunology MH - Male MH - Middle Aged MH - Myocardium/immunology MH - Retrospective Studies MH - Tissue Donors MH - Young Adult OTO - NOTNLM OT - Antibody-mediated rejection OT - Cardiac transplantation OT - Donor-specific antibody OT - Endomyocardial biopsy EDAT- 2014/12/03 06:00 MHDA- 2016/03/17 06:00 CRDT- 2014/12/03 06:00 PHST- 2014/07/09 00:00 [received] PHST- 2014/10/31 00:00 [revised] PHST- 2014/11/03 00:00 [accepted] PHST- 2014/12/03 06:00 [entrez] PHST- 2014/12/03 06:00 [pubmed] PHST- 2016/03/17 06:00 [medline] AID - S1054-8807(14)00143-4 [pii] AID - 10.1016/j.carpath.2014.11.001 [doi] PST - ppublish SO - Cardiovasc Pathol. 2015 May-Jun;24(3):168-72. doi: 10.1016/j.carpath.2014.11.001. Epub 2014 Nov 7.