Clinical and histological changes associated with corticosteroid therapy in IgG4-related tubulointerstitial nephritis

Objectives This study aimed to investigate the clinicopathological changes induced by corticosteroid therapy in immunoglobulin (Ig)G4-related tubulointerstitial nephritis (TIN). Methods We studied six IgG4-related TIN patients receiving renal biopsies before and after corticosteroid therapy. Their clinical data and histological findings were evaluated before and after therapy. Results Elevated serum creatinine levels rapidly improved after corticosteroid therapy except for two patients, in whom it persisted. Abnormal radiological findings improved in all patients, although focal cortical atrophy persisted in three. Histologically, TIN-like dense lymphoplasmacytic infiltration, interstitial fibrosis, IgG4-positive plasma cell, CD4+CD25+ T cell, and Foxp3+ cell infiltration were characteristic before therapy. After therapy, the area with cell infiltration decreased and regional fibrosis became evident in the renal interstitium. The number of IgG4-positive plasma cells and Foxp3+ cells significantly diminished even in the early stage of therapy, whereas low to moderate numbers of CD4+ and CD8+ T cells still infiltrated where inflammation persisted in the later stage. Conclusions Our study shows that persistent renal insufficiency associated with macroscopic atrophy and microscopic fibrosis is not so rare in IgG4-related TIN. Pathologically, the behavior of regulatory T cells during the clinical course is quite similar to that of IgG4-positive plasma cells, and the behavior pattern of those cells is distinctive.