The distinct pathogenesis of IgG4 Mickulicz's disease and Sjogren's syndrome in Japan; the role of IL-21 and IL-6

Maehara et al present an interesting study on ‘Interleukin-21 contributes to germinal centre formation and immunoglobulin G4 production in IgG4-related dacroadenitis and sialoadenitis, so-called Mickulicz's disease (MD)’.1 They have studied 12 Japanese patients with MD (IgG4-DS), 15 with Sjogren's syndrome (SS) and 15 healthy controls. The labial salivary biopsies (LSB) of 15 SS patients were chosen from a larger group of SS patients (n=66) based on the presence of ectopic germinal centres (GC) in 15 SS LSBs studied. All the MD patients were chosen on the basis of their elevated IgG4. The SS patients were chosen on the basis of ectopic GC in their biopsies. The mRNA expression of IL-21 and BCL-6 was significantly higher in MD than in SS labial salivary gland biopsies. The IL-21 was detected by immunohistochemistry in and around GC only in the MD patients. These results were consistent with the hypothesis that follicular T-helper cells (Tfh) play a key role in the formation of GC in MD. By contrast, IL-17 was not found in either SS or MD. This article extends a recent study by the same group2 in Kyushu that distinguished MD and SS by showing elevation of Th2 and Tregs (ie, IL4, IL10 and FoxP3 expression by immunohistochemistry); and IgG4 plasma cells in the MD labial biopsies. Over the past decade, this group has published a number of excellent papers on IgG4-related diseases, including sclerosing cholangitis, multicentric Castleman's disease and other lymphoproliferative disorders.3–5 The article is carefully presented by experts in the field, but …