Sarcolemmal Staining by Anti-C4d/C3d in Cardiac Transplant Endomyocardial Biopsies and Associated Serum HLA Antibodies and Pathologic Rejection

Abstract

Immunologic evidence of complement fixation in endomyocardial biopsies (EMB) is a feature used to assess pathologic antibody-mediated rejection in cardiac transplants. Uncommonly, sarcolemmal staining (SS) of myocytes is observed. The significance of this is unclear and under-investigated. This study aims to temporally correlate SS with changes in HLA antibodies and pathologic rejection. All EMBs that had SS by anti-C4d and/or C3d on immunofluorescence or immunohistochemistry (Figure 1) were identified via the laboratory information system between 10/1/2016 and 10/1/2019. The HLA antibodies and all other EMB results since time of transplant for each case were reviewed and temporally correlated to the biopsy that showed SS. 28 patients (mean: 31 yrs; range: 6-73 yrs) with 31 SS events were identified. Associated features are summarized in Table 1. Of note, 29/31 events of SS had HLA antibodies measured within a 2 week period before/after the time of biopsy. A temporally associated expansion of HLA Class I/II antibodies was noted in 12 (39%) cases. 21 (68%) cases had prior donor specific antibodies before EMB showing SS, with less immediate temporal association. Sarcolemmal staining of complement split products in EMBs was associated with a concurrent expansion in strength and/or breadth of HLA antibodies in 39% of cases. This is a novel observation that may partially explain the appearance of SS by immunologic assays. Further investigation is required to fully elucidate the significance of SS in EMB.