Expression of VWF and Interferon γ in renal allograft biopsies and correlation with inflammatory cells. Single center experience.
Keywords:Renal allograft biopsy; VWF; IFNγ; PCR; Kidney transplantation
Objective: Gene expression profiling by microarrays or RT PCR has been studied in certain western centers to enhance the diagnostic accuracy of allograft biopsy, however, such sophisticated tests are difficult to apply in developing countries. This study was conducted to evaluate the expression of von Willebrand factor (VWF) and Interferon-gamma (IFNγ) as an end PCR product in renal allograft biopsy with different pathological categories.
Methods: Forty-nine (49) indicated renal allograft biopsies were analyzed histologically by the Banff 2017 classification, inflammatory cell infiltration was analyzed by immunohistochemistry study for CD4, CD8, CD16, and CD68 markers, and a fresh tissue used for molecular study.
Results: The biopsy findings were acute T-cell mediated rejection (A-TCMR) 30.6%, interstitial fibrosis and tubular atrophy 22.4%, C4d-Transplant glomerulopathy 12.2%, calcineurin inhibitor toxicity 10.2%, C4d+antibody mediated rejection 10.2% and normal histology 14.3%. The only significant difference in VWF expression was between acute TCMR and normal, P=0.01, Spearman’s correlation also showed a significant relationship between VWF and acute TCMR (r=0.53, P=0.01), and VWF was found to correlate with the numbers of interstitial CD4+ (r=0.29, P=0.03) and CD68+ (r=0.37, P=0.007) cells. IFNγ expression was significant in acute TCMR versus normal, P=0.009. Spearman’s pair-wise testing showed that INFγ correlated with CD8 in both the glomerular (r=0.38, P=0.006) and interstitial (r=0.30, P=0.04) compartments and with CD16+ interstitial cells (r=0.36, P=0.01).
Conclusions: Molecular and immunohistochemistry data of this study distinguish acute TCMR from other forms of transplant pathology and mildly dysfunctional kidneys with normal histology.
2. Zhou J, D'Agati V, Laszik Z, Nadasdy T. Silva's diagnostic renal pathology. Cambridge: Cambridge University; 2016.
3. Parajuli S, Aziz F, Garg N, Panzer S, Joachim E, Muth B et al. Histopathological characteristics and causes of kidney graft failure in the current era of immunosuppression. World Journal of Transplantation. 2019;9(6):123-1
4. Williams W, Taheri D, Tolkoff-Rubin N, Colvin R. Clinical role of the renal transplant biopsy. Nature Reviews Nephrology. 2012;8(2):110-121.
5. Haas M, Loupy A, Lefaucheur C, Roufosse C, Glotz D, Seron D et al. The Banff 2017 Kidney Meeting Report: Revised diagnostic criteria for chronic active T cellâ€“mediated rejection, antibodyâ€mediated rejection, and prospects for integrative endpoints for nextâ€generation clinical trials. American Journal of Transplantation. 2018;18(2):293-3
6. Mengel M, Sis B, Halloran P. SWOT Analysis of Banff: Strengths, Weaknesses, Opportunities and Threats of the International Banff Consensus Process and Classification System for Renal Allograft Pathology. American Journal of Transplantation. 2007;7(10):2221-2226.
7. Sis B, Jhangri G, Bunnag S, Allanach K, Kaplan B, Halloran P. Endothelial Gene Expression in Kidney Transplants with Alloantibody Indicates Antibody-Mediated Damage Despite Lack of C4d Staining. American Journal of Transplantation. 2009;9(10):2312-2323.
8. Reeve J, Einecke G, Mengel M, Sis B, Kayser N, Kaplan B et al. Diagnosing Rejection in Renal Transplants: A Comparison of Molecular- and Histopathology-Based Approaches. American Journal of Transplantation. 2009;9(8):1802-1810.
9. Halloran P, Reeve J, Akalin E, Aubert O, Bohmig G, Brennan D et al. Real Time Central Assessment of Kidney Transplant Indication Biopsies by Microarrays: The INTERCOMEX Study. American Journal of Transplantation. 2017;17(11):2851-2862.
10. Roufosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen K, Horsfield C et al. A 2018 Reference Guide to the Banff Classification of Renal Allograft Pathology. Transplantation. 2018;102(11):1795-1814.
11. Bonthron D, Handin R, Kaufman R, Wasley L, Orr E, Mitsock L et al. Structure of pre-pro-von Willebrand factor and its expression in heterologous cells. Nature. 1986;324(6094):270-273.
12. Kim S, Kim YK, Lee H, Cho JE, Kim HY et al. Interferon gamma mRNA quantitative real-time polymerase chain reaction for the diagnosis of latent tuberculosis: a novel interferon gamma release assay. Diagn Microbiol Infect Dis. 2013, 75, 68-72.
13. Halloran P, Venner J, Madill-Thomsen K, Einecke G, Parkes M, Hidalgo L et al. Review: The transcripts associated with organ allograft rejection. American Journal of Transplantation. 2017;18(4):785-795.
14. Adam B, Afzali B, Dominy K, Chapman E, Gill R, Hidalgo L et al. Multiplexed color-coded probe-based gene expression assessment for clinical molecular diagnostics in formalin-fixed paraffin-embedded human renal allograft tissue. Clinical Transplantation. 2016;30(3):295-305.
15. dos Santos D, Campos E, Saraiva CÃ¢mara N, David D, Malheiros D. Compartment-specific expression of natural killer cell markers in renal transplantation: immune profile in acute rejection. Transplant International. 2015;29(4):443-452.
16. Divella C, Rossini M, Loverre A, Schena A, Maiorano A, Gesualdo V et al. Immunohistochemical characterization of glomerular and tubulointerstitial infiltrates in renal transplant patients with chronic allograft dysfunction. Nephrology Dialysis Transplantation. 2010;25(12):4071-4077.
17. Hayde N, Bao Y, Pullman J, Ye B, Calder R, Chung M et al. The Clinical and Genomic Significance of Donor-Specific Antibodyâ€“Positive/C4d-Negative and Donor-Specific Antibodyâ€“Negative/C4d-Negative Transplant Glomerulopathy. Clinical Journal of the American Society of Nephrology. 2013;8(12):2141-2148.
18. Lefaucheur C, Viglietti D, Hidalgo L, Ratner L, Bagnasco S, Batal I et al. Complement-Activating Anti-HLA Antibodies in Kidney Transplantation: Allograft Gene Expression Profiling and Response to Treatment. Journal of the American Society of Nephrology. 2017;29(2):620-635.
19. Batal I, Azzi J, El-Haddad N, Riella L, Lunz J, Zeevi A et al. Immunohistochemical markers of tissue injury in biopsies with transplant glomerulitis. Human Pathology. 2012;43(1):69-80.
20. Kurian S, Williams A, Gelbart T, Campbell D, Mondala T, Head S et al. Molecular Classifiers for Acute Kidney Transplant Rejection in Peripheral Blood by Whole Genome Gene Expression Profiling. American Journal of Transplantation. 2014;14(5):1164-1172.
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