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
Alessandro Gambella,
Antonella Barreca,
Simona Osella-Abate,
Emanuel Bottasso,
Manuela Maria Giarin,
Mauro Papotti,
Luigi Biancone,
Jasna Metovic,
Giammarco Collemi,
Paola Cassoni,
Luca Bertero
Affiliations
Alessandro Gambella
Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
Antonella Barreca
Pathology Unit, “Città della Salute e della Scienza di Torino” University Hospital, Via Santena 7, 10126 Turin, Italy
Simona Osella-Abate
Molecular Pathology Unit, “Città della Salute e della Scienza di Torino” University Hospital, Via Santena 5, 10126 Turin, Italy
Emanuel Bottasso
Pathology Unit, “Città della Salute e della Scienza di Torino” University Hospital, Via Santena 7, 10126 Turin, Italy
Manuela Maria Giarin
Pathology Unit, “Città della Salute e della Scienza di Torino” University Hospital, Via Santena 7, 10126 Turin, Italy
Mauro Papotti
Pathology Unit, Department of Oncology, University of Turin, Via Santena 7, 10126 Torino, Italy
Luigi Biancone
Renal Transplantation Center ‘A. Vercellone’, Division of Nephrology Dialysis and Transplantation, Department of Medical Sciences, Città della Salute e della Scienza Hospital and University of Turin, 10124 Torino, Italy
Jasna Metovic
Pathology Unit, Department of Oncology, University of Turin, Via Santena 7, 10126 Torino, Italy
Giammarco Collemi
Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
Paola Cassoni
Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
Luca Bertero
Pathology Unit, Department of Medical Sciences, University of Turin, Via Santena 7, 10126 Turin, Italy
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.
