The immunohistochemical expression of von Willebrand factor, T-cadherin, and Caveolin-1 is increased in kidney allograft biopsies with antibody-mediated injury

• Published in: Clinical and experimental nephrology Vol. 25; no. 3; pp. 305 - 314
• Main Authors: Teixeira, André Costa, Távora, Fábio, de Deus e Silva, Melissa Lou Fagundes, Prado, Renan Martins Gomes, de Matos Esmeraldo, Ronaldo, de Sandes-Freitas, Tainá Veras
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01-03-2021; Springer Nature B.V
• Subjects: Antibodies; Atrophy; Biopsy; Cadherins; Capillaries; Caveolin; Caveolin-1; Fibrosis; Graft rejection; Immunohistochemistry; Inflammation; Kidney transplantation; Medicine; Medicine & Public Health; Microvasculature; Nephrology; Original Article; T-cadherin; Urology; Von Willebrand factor; Caveolin-1; Immunohistochemistry; T-cadherin; Von willebrand factor; Antibody-mediated rejection
• ISSN: 1342-1751; 1437-7799
• DOI: 10.1007/s10157-020-01994-6

Background
There are only a few reports evaluating the applicability of endothelial-damage markers analysis by immunohistochemistry (IHC) in kidney allograft samples. This study analyzed the expression of Caveolin-1 (Cav), von Willebrand factor (Vwf), and T-cadherin (Cad) in kidney biopsies and their association with antibody-mediated injury.
Methods
In this retrospective study, 114 cases with antibody-mediated changes (Banff, 2020) and 72 with interstitial fibrosis/tubular atrophy were selected. IHC for Cav, Vwf and Cad was performed and evaluated according to their qualitative expression in peritubular capillaries. The cases were grouped according to the presence of microvascular inflammation (MVI), donor-specific antibodies (DSA), C4d positivity and antibody-mediated rejection (AMR). A level of significance < 0.05 was adopted.
Results
Vwf expression was associated with MVI (
p
 < 0.001), DSA (
p
 = 0.016), C4d (
p
 < 0.001) and AMR (
p
 < 0.001), and was higher in DSA+/C4d+ cases despite MVI (
p
 < 0.001). The expression of Cad correlated with MVI (
p
 = 0.015), C4d (
p
 = 0.005) and AMR (
p
 = < 0.001). Cad was more expressed in chronic AMR compared with acute/active cases (
p
 = 0.001). Cav expression was associated with MVI (
p
 = 0.029) and AMR (
p
 = 0.016) and was also higher in chronic AMR (
p
 = 0.049). A combined score of Vwf and Cad was higher in AMR when compared with C4d without rejection and IF/TA cases (
p
 < 0.001).
Conclusion
Vwf, Cad and Cav expression shows association with antibody-mediated injury and may be helpful to support AMR diagnosis.