RESUMO
Fibrillary glomerulonephritis (FGN) is a rare glomerular disease characterized by a challenging diagnostic workup requiring ultrastructural identification of 20 nm-thick randomly oriented fibrillar deposits. However, the recent introduction of DNAJB9 as a putative diagnostic marker of FGN could thoroughly improve this diagnostic scenario. This study aims to assess the DNAJB9 immunohistochemical expression in a large series of FGN cases and to eventually confirm its role as a diagnostic marker of FGN. We evaluated the immunohistochemical expression of DNAJB9 (Rabbit Polyclonal, ThermoFisher) in a series of 77 FGN and 128 non-FGN cases diagnosed between January 1992 and June 2022 at the Pathology Unit of the AOU Città della Salute e della Scienza Hospital. DNAJB9 was expressed in 73 of the 74 evaluable FGN cases, mostly showing a strong glomerular positivity (68 cases). Additionally, DNAJB9 resulted positive in all challenging scenarios [early-stage (6), congophilic (4), combined (4), and uncertain (4) cases of FGN)]. DNAJB9 was negative in all non-FGN cases, eventually resulting in a specificity of 100% and sensitivity of 99%. In conclusion, we confirmed the role of DNAJB9 as a diagnostic marker of FGN. Its adoption in the clinical routine will allow a faster, more feasible, and more accurate FGN diagnosis.
RESUMO
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.