New insights into the pathophysiology of IgG4-related disease and markers of disease activity

Introduction: Recently, IgG4-related disease (IgG4-RD) has become a well-recognized clinical entity, although its causes are still not well understood. The pathophysiology of IgG4-RD has been reported from a variety of aspects. Areas covered: In this review, we outline a number of recent advances in our understanding of the pathogenesis of IgG4-RD, divided according to acquired immunology and innate immunology and other topics. Furthermore, we also focus on some proposed markers of disease activity of IgG4-RD. Expert commentary: One striking advance made recently is the identification of novel autoantigens of IgG4-RD. At the onset of IgG4-RD, various T cell side factors such as Tfh, Th2 cells are at work, in addition to B cell side factors like plasmablasts and plasma cells, and innate immunology via TLR and M2 macrophages. The efficacy of B cell depletion therapy using rituximab has been reported, with the establishment of steroid-sparing therapies targeting other molecules also anticipated.