Abnormal B Lymphocyte Activation and Function in Systemic Sclerosis

Systemic sclerosis (SSc) is characterized by tissue fibrosis and autoimmunity. Although the pathogenic relationship between autoimmunity and clinical manifestations of SSc remains unknown, SSc patients display abnormal immune responses including the production of disease-specific autoantibodies. Previous studies have demonstrated that B cells play a critical role in systemic autoimmunity and disease expression through various functions such as induction of the activation of other immune cells in addition to autoantibody production. CD19 is a crucial regulator of B cell activation. Recent studies demonstrated that B cells from SSc patients showed an up-regulated CD19 signaling pathway that induced SSc-specific autoantibody production in SSc mouse models. CD19 transgenic mice lost tolerance for autoantigen and generated autoantibodies spontaneously. B cells from SSc patients exhibited an overexpression of CD19 that induced SSc-specific autoantibody production in transgenic mice. Moreover, SSc patients displayed intrinsic B cell abnormalities characterized by chronic hyper-reactivity of memory B cells, which was possibly due to CD19 overexpression. Similarly, B cells from a tight-skin mouse, a genetic model of SSc, showed augmented CD19 signaling. In bleomycin-induced SSc mouse models, endogenous ligands for toll-like receptor 4 induced by bleomycin stimulated B cells to produce various fibrogenic cytokines and autoantibodies. Remarkably, the loss of CD19 resulted in the inhibition of B cell hyper-reactivity and autoantibody production, which are associated with improvements in fibrosis and a parallel decrease in fibrogenic cytokine production by B cells. Taken together, the findings suggest that altered B cell function may result in tissue fibrosis as well as autoimmunity in SSc.

A case of Successfully Operated Pelvic Arteriovenous Malformation / 日本心臓血管外科学会雑誌

A lower abdominal tumor with thrill and bruit was pointed out in a 59-year-old female. Angiography showed a pelvic arteriovenous malformation (AVM) with remarkably dilated vessels resembling an aneurysm. Feeding arteries for this AVM originated from the right internal iliac artery, right lumbar artery and right renal artery, and drainage blood flowed into the inferior <i>vena cava</i> from the dilated vessel via a large vein. At operation the right internal iliac artery and right lumbar artery were ligated and the dilated vessel with AVM, which connected with the right renal artery, was resected. An angiography 16 days after the operation revealed the normal arteries without AVM and the right internaal iliac artery filled through collateral arteries. Recently catheter embolization in frequently the first choice for treatment of AVM. However, in the case of AVM with aneurysmal dilated vessels, surgical resection should be selected.