title: T-bet-positive mononuclear cell infiltration is associated with transplant glomerulopathy and interstitial fibrosis and tubular atrophy in renal allograft recipients.
abstract: OBJECTIVE
  We aimed to study the role of T-bet-positive mononuclear cell infiltration in different compartments of kidney graft tissues in patients with chronic transplant glomerulopathy, interstitial fibrosis and tubular atrophy, and stable graft function.
  
  
  METHODS
  There were 80 living-related renal transplant recipients included (chronic transplant glomerulopathy, n = 28; interstitial fibrosis and tubular atrophy, n = 28; stable graft function, n = 24). Histologic characteristics and scoring for peritubular capillaritis, glomerulitis, interstitial fibrosis and tubular atrophy, and intimal arteritis were performed according to Banff 2007 classification and compared between the groups. Immunohistologic staining was performed for transcription factor T-bet, T-bet mononuclear cells were counted, and T-bet infiltration score was compared between groups.
  
  
  RESULTS
  Patients in different groups had similar clinical profiles and human leukocyte antigen mismatches, except the groups differed in serum creatinine and proteinuria. The prevalence and scoring of peritubular capillaritis and glomerulitis were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy (P = .001) and stable graft function (P < .001). Tubulitis was observed in 6 patients (21.4%) with chronic transplant glomerulopathy but no patients with interstitial fibrosis and tubular atrophy. The C4d/donor-specific antibody was positive in 100% patients with chronic transplant glomerulopathy, 0% patients with interstitial fibrosis and tubular atrophy, and 4.1 % patients with stable graft function. Interstitial fibrosis and tubular atrophy was seen in 100% patients who had interstitial fibrosis and tubular atrophy; in patients who had chronic transplant glomerulopathy, 24 patients (85.7%) had interstitial fibrosis and 78.5% patients had tubular atrophy. The degree and severity of T-bet-positive cell infiltration were significantly higher in chronic transplant glomerulopathy than interstitial fibrosis and tubular atrophy or stable graft function; however, 85% patients with interstitial fibrosis and tubular atrophy also had T-bet-positive infiltration, suggesting a role of T-bet-positive cells in interstitial fibrosis and tubular atrophy.
  
  
  CONCLUSIONS
  Chronic transplant glomerulopathy is a consequence of chronic active immune-mediated injury. Interstitial fibrosis and tubular atrophy may be associated with T-bet-positive mononuclear cell infiltration in the peritubular region. The T-bet infiltration should be evaluated in patients with chronic allograft injury.
authors: From the Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors: Brijesh
authors: B
authors: Yadav
authors: Narayan
authors: N
authors: Prasad
authors: Vinita
authors: V
authors: Agrawal
authors: Manoj
authors: M
authors: Jain
authors: Vikas
authors: V
authors: Agarwal
authors: Akhilesh
authors: A
authors: Jaiswal
authors: Dharmendra
authors: D
authors: Bhadauria
authors: R K
authors: RK
authors: Sharma
authors: Amit
authors: A
authors: Gupta
mesh_terms: D002908:Chronic Disease; D006085:Graft Survival; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000473:pathology*; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology*; D016030:Kidney Transplantation; D007684:Kidney Tubules / Q000473:pathology; D007963:Leukocytes, Mononuclear / Q000473:pathology*; D019520:Living Donors; D011183:Postoperative Complications