Pathogenesis of IgG4-Related Kidney Disease

Abstract

IgG4-related disease (IgG4-RD) is a systemic condition that affects various organs. The serological features and histological changes are similar among subsets of IgG4-RD, which differ principally in the specific target organs affected. Common pathogenetic variables are believed to underlie IgG4-RD, regardless of the organs involved. In IgG4-RKD (IgG4-related kidney disease), a high level of serum IgG4 is a highly characteristic feature. Plasma cell-rich tubulointerstitial nephritis (TIN) with increased numbers of IgG4-positive plasma cells occurring in the setting of storiform fibrosis are distinct histological features. The analysis of mRNA expression in the kidneys of patients with IgG4-RKD showed an elevated production of IL-10 and TGF-β, similar to that observed in other target organs. These results suggest important roles for type 2 helper T cells (Th2) and regulatory T cells (Treg). In view of these data, a “modified Th2 response” related to an allergic reaction has been suggested to be the immunological background for IgG4-RD. On the other hand, certain immunohistological findings, such as immune deposits limited to the affected tubulointerstitium and associated with plasma cell infiltration, have been attributed to an autoimmune etiology. Furthermore, the mechanism behind the formation of characteristic fibrosis observed in IgG4-RKD has not yet been identified. The fact that treatment with anti-CD20 antibodies leads to a prompt clinical and serologic improvement of IgG4-RD underscores the significance of B cell activation in the pathogenesis of IgG4-RD. In short, the experimental and clinical evidence to date imply a complex pathophysiology for IgG4-RKD in which multiple elements of the immune system participate.