Expression of VWF and Interferon γ in renal allograft biopsies and correlation with inflammatory cells; Single center experience

Abstract

Objective: Gene expression profiling by microarrays or RT PCR had 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 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  (IF/TA) 22.4%, C4d-Transplant glomerulopathy (TG) 12.2%, calcineurin inhibitor toxicity (CNI) 10.2%, C4d+antibody mediated rejection (AMR) 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). Conclusion: our molecular and IHC data distinguish acute TCMR from other forms of transplant pathology and mildly dysfunctional kidneys with normal histology.