Several studies have shown that autoantibodies are heavily

mutated and back mutation of mutated human V genes to the germline sequences resulted in a loss of antigen binding [20–22]. However, other reports did not support these findings [23–25]. Some studies have shown a low rate of somatic mutation in autoantibodies of patients with SS [17, 26, 27]. In another study, an increased rate (19.6%) of unmutated clones was reported in the parotid gland specimen from a patient with SS [18]. In addition, VH gene analyses of non-Hodgkin lymphomas in patients with SS have shown that neoplastic B cell populations are often unmutated [14–28]. Our finding that B cells infiltrating inflammatory lesions of patients with SS possess less mutated VH genes is in line with these observations and supports the hypothesis check details that some germline or less mutated genes may play a role in the development of this autoimmune disease. Moreover, CH5424802 mouse autoantibodies encoded by such genes fail to be deleted in patients with SS. IgG4-related sclerosing sialadenitis is a chronic inflammatory disorder characterized by a dense infiltration of IgG4-positive plasma cells. As treatment with steroids is very effective, an autoimmune mechanism is highly implicated in the aetiology of IgG4-related sclerosing sialadenitis. In this study, we

showed that VH fragments of IgG4-related sclerosing sialadenitis and SS cases shared a common characteristics, a high rate of unmutated VH clones probably derived from the VH3 family. This finding suggests that an autoimmune mechanism similar to that of SS may also be responsible to the development of IgG4-related sclerosing sialadenitis. In conclusion, we studied VH usage and VH

somatic hypermutation in SS and IgG4-related sclerosing sialadenitis using sialolithiasis tissues as a control. The VH fragments, especially those of the VH3 family, were often unmutated when compared with those of the sialolithiasis cases. This finding will provide insight into the pathogenesis of SS and IgG4-related sclerosing sialadenitis. H. S., T. J., K. S, and H. I. designed research; H.S., F.O., and S.M. performed research; H.S., F. O., S. M., and H.I. analyzed data; and H. S. and H.I. wrote the paper. Authors thank Dr Hitoshi Miyachi, Aichi-Gakuin University School of Dentistry, for his valuable advice and Mr Takeo PtdIns(3,4)P2 Sakakibara for his technical assistance. H. Sakuma and F. Okumura contributed equally to the study and should both be regarded as first authors. This study has no conflicts of interest. Data S1 Sequence analysis of Sjogren’s syndrome cases. Data S2 Sequence analysis of IgG4-related sclerosing sialadenitis cases. Data S3 Sequence analysis of sialolithiasis cases. Please note: Wiley-Blackwell are not responsible for the content or functionality of any supporting materials supplied by the authors. Any queries (other than missing material) should be directed to the corresponding author for the article.