OBJECTIVES: 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.
OBJECTIVES: 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: Miao Zheng; Pan Zhou; Kai Zheng; Li Meng; Xian Liu; Mengdi Chu; Jie Lu; Lingli Dong Journal: Am J Transl Res Date: 2016-02-15 Impact factor: 4.060
Authors: Elisabeth G D Stribos; Signe Holm Nielsen; Susanne Brix; Morten Asser Karsdal; Marc A Seelen; Harry van Goor; Stephan J L Bakker; Peter Olinga; Henricus A M Mutsaers; Federica Genovese Journal: PLoS One Date: 2017-04-21 Impact factor: 3.240