title: Does treatment with corticosteroids and cyclosporine reduce transglutaminase type 2 expression in the renal tissue of patients with membranous nephropathy?
abstract: OBJECTIVE
  Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in adults. Transglutaminase type 2 (TG2) contributes to renal scarring through altering extracellular matrix homeostasis. In this study we hypothesized that immunosuppressive treatment would downregulate TG2 expression leading to reduced fibrosis, and subsequently TG2 would have value as a biomarker of progression of MN.
  
  
  METHODS
  TG2 expression was studied by immunofluorescence in kidney biopsy sections from 32 patients with MN and was compared to control biopsies. All patients were subsequently treated by a combination of cyclosporine and prednisolone for at least 24 months with a repeat biopsy taken in 14 patients.
  
  
  RESULTS
  Twenty-two out of 32 patients showed stable renal function, whereas 10 showed doubling of baseline serum creatinine and 5 of them reached end-stage renal disease during the 5-year follow-up. At the end of the follow-up, 22 out of 32 patients were in remission of nephrotic syndrome. TG2 immunostaining was increased in sections from patients with MN compared to healthy controls (p = 0.0002). TG2 at diagnosis was more intense in patients with severer interstitial fibrosis and advanced glomerular sclerosis. TG2 significantly increased in most patients in the repeat biopsies after treatment (p < 0.0001), whereas patients who showed a marked increase in interstitial fibrosis in the repeat biopsy had significantly more TG2 expression in the first biopsy (p = 0.02).
  
  
  CONCLUSIONS
  TG2 expression is increased in MN patients and continues to increase despite immunosuppressive treatment. However, early detection of TG2 might be of value in MN since increased TG2 production seems to precede extensive interstitial fibrosis.
authors.affiliation: Department of Nephrology and Renal Transplantation, University Hospital of Patras, Patras, Greece.
authors.forename: Marios
authors.initials: M
authors.lastname: Papasotiriou
authors.forename: Pantelitsa
authors.initials: P
authors.lastname: Kalliakmani
authors.forename: Linghong
authors.initials: L
authors.lastname: Huang
authors.forename: Miltiadis
authors.initials: M
authors.lastname: Gerolymos
authors.forename: Dimitrios S
authors.initials: DS
authors.lastname: Goumenos
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000627:therapeutic use*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D019204:GTP-Binding Proteins / Q000378:metabolism*; D015433:Glomerulonephritis, Membranous / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000627:therapeutic use*; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D018709:Statistics, Nonparametric; D011503:Transglutaminases / Q000378:metabolism*; D016896:Treatment Outcome
chemical_list: D000893:Anti-Inflammatory Agents; D015415:Biomarkers; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011239:Prednisolone; D003404:Creatinine; D000091345:Protein Glutamine gamma Glutamyltransferase 2; D011503:Transglutaminases; D019204:GTP-Binding Proteins