Caveolin-1 in Kidney Chronic Antibody-Mediated Rejection: An Integrated Immunohistochemical and Transcriptomic Analysis Based on the Banff Human Organ Transplant (B-HOT) Gene Panel

Abstract

Caveolin-1 overexpression has previously been reported as a marker of endothelial injury in kidney chronic antibody-mediated rejection (c-ABMR), but conclusive evidence supporting its use for daily diagnostic practice is missing. This study aims to evaluate if Caveolin-1 can be considered an immunohistochemical surrogate marker of c-ABMR. Caveolin-1 expression was analyzed in a selected series of 22 c-ABMR samples and 11 controls. Caveolin-1 immunohistochemistry proved positive in peritubular and glomerular capillaries of c-ABMR specimens, irrespective of C4d status whereas all controls were negative. Multiplex gene expression profiling in c-ABMR cases confirmed Caveolin-1 overexpression and identified additional genes (n = 220) and pathways, including MHC Class II antigen presentation and Type II interferon signaling. No differences in terms of gene expression (including Caveolin-1 gene) were observed according to C4d status. Conversely, immune cell signatures showed a NK-cell prevalence in C4d-negative samples compared with a B-cell predominance in C4d-positive cases, a finding confirmed by immunohistochemical assessment. Finally, differentially expressed genes were observed between c-ABMR and controls in pathways associated with Caveolin-1 functions (angiogenesis, cell metabolism and cell–ECM interaction). Based on our findings, Caveolin-1 resulted as a key player in c-ABMR, supporting its role as a marker of this condition irrespective of C4d status.

Spectrum of Kidney Injury Following COVID-19 Disease: Renal Biopsy Findings in a Single Italian Pathology Service

“…No electron-dense deposits and viral particles were observed on EM. Caveolin-1 (Cav1) immunohistochemistry demonstrated diffuse positivity both in peritubular and glomerular capillaries, as previously reported by our group in TMA [ 98 ].…”

“…Original slides and ultrastructural images were retrieved and reviewed by expert renal pathologists. At the time of diagnosis, histopathological, immunohistochemical (IHC), and immunofluorescence (IF) analyses were performed according to our laboratory clinical protocols, as previously described [ 98 ]. IHC and IF antibodies are detailed in Supplementary Methods .…”

The Proteome of Antibody-Mediated Rejection: From Glomerulitis to Transplant Glomerulopathy

“…A recent transcriptomic and immunohistochemical study highlighted caveolin-1 as potential marker of chronic ABMR, found on the endothelium surface of both glomeruli and peritubular capillaries [50]. Herein we did not detect caveolin-1 by mass spectrometry, and so our findings could not support this result.…”

Extracorporeal Photopheresis Reduces Fibrotic and Inflammatory Transcriptomic Biological Marker of Chronic Antibody-mediated Kidney Rejection

“…19–21 Indeed, 2 studies reported that donor CAV1 single nucleotide variation could influence graft fibrosis and long-term outcome after kidney transplantation. 20,21 In a recent study, Gambella et al 22 reported that Caveolin-1 is overexpressed in cABMR and could be a key marker in patients with cABMR. Overexpression of CAV1 could thus be a compensatory mechanism to the fibrotic lesions induced by cABMR but both its kinetics and prognostic significance remain to be determined.…”