title: Endothelial injury in transplant glomerulopathy is correlated with transcription factor T-bet expression.
abstract: Transplant glomerulopathy is an important cause of late graft loss. Inflammatory lesions including glomerulitis and peritubular capillaritis, suggestive of endothelial injury, are prominent in this condition but the mechanism underlying this inflammation remains unclear. Here we measured the expression of T-bet (a member of the T-box family of transcription factors regulating Th1 lineage commitment) and its relationship with inflammation in 70 patients with transplant glomerulopathy. Within this cohort, 32 patients were diagnosed with transplant glomerulopathy, 23 with interstitial fibrosis/tubular atrophy, and 15 with stable grafts. There was a significant increase in T-bet expression in both glomerular and peritubular capillaries of the transplant glomerulopathy group. This expression was strongly correlated with CD4(+), CD8(+), and CD68(+) cell infiltration within glomerular and peritubular capillaries. The expression of GATA3, a Th2 regulator, was rarely found in the transplant glomerulopathy group. Transplant glomerulopathy was associated with diffuse peritubular capillary dilation without reduced capillary density. Moreover, the degree of capillary dilation was significantly correlated with the number of infiltrating CD68(+) cells. Since endothelial injury is a typical lesion that follows alloantibody reactivity, our results suggest that T-bet is involved in the pathogenesis of this glomerulopathy.
authors.affiliation: Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. sunqiquan@hotmail.com
authors.forename: Qiquan
authors.initials: Q
authors.lastname: Sun
authors.forename: Mingchao
authors.initials: M
authors.lastname: Zhang
authors.forename: Kenan
authors.initials: K
authors.lastname: Xie
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.forename: Caihong
authors.initials: C
authors.lastname: Zeng
authors.forename: Minlin
authors.initials: M
authors.lastname: Zhou
authors.forename: Zhihong
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004730:Endothelium, Vascular / Q000293:injuries / Q000378:metabolism / Q000473:pathology; D005260:Female; D050990:GATA3 Transcription Factor / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D020825:T-Box Domain Proteins / Q000378:metabolism*; D000098815:T-bet Transcription Factor
chemical_list: D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor