An amplification of IL-10 and TGF-beta in patients with IgG4-related tubulointerstitial nephritis

IgG4-related tubulointerstitial nephritis (TIN) shows characteristic serum IgG4 elevation and increased IgG4-positive plasma cells in the renal interstitium, and inclusion of TIN as an IgG4-related systemic disease has been suggested. IgG4 is the rarest IgG subclass and is a Th2-dependent isotype with low affinity for target antigen. Although the pathogenesis of this disease has not been elucidated, positive serum immune complex and hypocomplementemia in some patients with this disease suggest that immune complex mechanisms are involved in the causation of this disease.We selected 20 cases of histological diagnosed TIN. These cases were etiologically different and included 4 cases of IgG4-related TIN. We extracted RNA from paraffin embedded biopsied kidney and evaluated expression levels of various cytokines for each case by real time PCR.Comparison of cytokine production patterns among different disease-associated TINs revealed that IgG4-related TIN exhibited a quite distinct pattern. On the one hand, there was no expression of IL-2, IFN-gamma IL-17 and IL-6, whereas production of IL-4, IL-10 and TGF-beta was, on the other hand, remarkably increased in IgG4-related TIN.Based on these cytokine production results, Th2 and Treg appear to play a central role in IgG4-related TIN.