title: Immunohistological analysis for immunological response and mechanism of interstitial fibrosis in IgG4-related kidney disease.
abstract: OBJECTIVE
  Our study aimed to clarify the immunological characteristics and the mechanism of interstitial fibrosis in immunoglobulin G4-related kidney disease (IgG4-RKD) by the immunohistological analysis.
  
  
  METHODS
  Immunohistological study was performed in the biopsied renal tissues of 16 IgG4-RKD, 16 Sjögren syndrome (SJS), and 17 idiopathic tubulointerstitial nephritis (ITIN) patients using antibodies against IgG; IgG1; IgG4; CD38; CD3; C-X-C chemokine receptor type 3 (CXCR3); chemokine (C-C motif) receptor 4 (CCR4); forkhead box 3 (Foxp3); Type I, Type III, Type IV, and Type VI collagens; and transforming growth factor (TGF)-β1.
  
  
  RESULTS
  Interstitial lymphoplasmacytic and eosinophilic infiltration and the severity of interstitial fibrosis were greater in IgG4-RKD than SJS and ITIN. The ratio of CXCR3+/CD3 + cells was greater in SJS as compared with that in IgG4-RKD and ITIN. The ratio of CCR4+/CD3 + cells was not different among the three diseases. The ratio of interstitial IgG4+/IgG+ plasma cells, Foxp3+/CD3 + cells, and TGF-β1 + cells/total infiltrating cells was higher in IgG4-RKD than SJS and ITIN. There was a positive correlation between the ratio of Foxp3+/CD3 + cells and that of IgG4+/IgG+ plasma cells in IgG4-RKD. Significant correlation was found between the ratio of Foxp3+/CD3 + cells and that of TGF-β1 + cells/total infiltrating cells in IgG4-RKD. Foxp3 + cells and TGF-β1 + cells were colocalized in the interstitium in IgG4-RKD. The significant correlation between the ratio of TGF-β1 + cells/total infiltrating cells and the severity of fibrosis was noticed in IgG4-RKD. The interstitial distribution of type III collagen and type IV collagen was higher in IgG4-RKD than in SJS.
  
  
  CONCLUSIONS
  Our results suggest that regulatory T-cells (Tregs) may play a central role in IgG4 production in the interstitium and TGF-β1 induced by Tregs may play a pivotal role in the interstitial fibrosis including type III and type IV collagens in IgG4-RKD.
authors.affiliation: Division of Nephrology and Rheumatology, Department of Internal Medicine, Fukuoka University , Fukuoka , Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Kawamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Hisano
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Nakashima
authors.forename: Morishige
authors.initials: M
authors.lastname: Takeshita
authors.forename: Takao
authors.initials: T
authors.lastname: Saito
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D018925:Chemokines / Q000378:metabolism*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology* / Q000378:metabolism; D007150:Immunohistochemistry; D007668:Kidney / Q000276:immunology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology
chemical_list: D018925:Chemokines; D007074:Immunoglobulin G
keywords: IgG4-related kidney disease; Storiform fibrosis; Th2 cell; Treg