Spontaneous Regression of Colonic Lesions in Adult T-cell Leukemia

A 74-year-old man was admitted to our hospital because of diarrhea. Serum anti-HTLV-1 antibody was positive without abnormal lymphocytes. Colonoscopy demonstrated a edematous and congested mucosa with erosions, and ulcers in the region extending from the cecum to rectum. Biopsy specimens showed diffuse infiltration of abnormal lymphocytes positive for T-cell markers in the lamina propria. Conservative therapy was provided but no chemotherapy because of improvement of diarrhea within two weeks. A repeat colonoscopy 6 months later revealed scars without erosions or ulcers. Eight months after first admission, the patient was readmitted to our hospital because of acute ATL crisis, and died of hepatic involvement 7 days later. Colonic lesions associated with ATLS may show spontaneous regression and recurrence

Anti-cytokine autoantibodies are ubiquitous in healthy individuals

AbstractAnti-cytokine autoantibodies in healthy individuals have been widely reported but the occurrence is variable and inconstant. We hypothesized that cytokine-binding in vivo may explain their variable and infrequent detection. Therefore, we focused on the detection of the cytokine-autoantibody complexes and found that anti-cytokine autoantibody to IL-2, IL-8, tumor necrosis factor-α, vascular endothelial growth factor and granulocyte-colony stimulating factor were present in all 15 individuals evaluated, while those to IL-3, osteopontin and macrophage-colony stimulating factor were not detected in anyone. Autoantibodies against IL-4, IL-6, IL-10, and interferon-gamma were variously detected. Thus, we discovered that anti-cytokine autoantibodies to multiple cytokines are ubiquitous in healthy individuals

Subserosal Inflammatory Pseudotumor Causing Intussusception

We present an adult case of intussusception caused by subserosal inflammatory pseudotumor of the terminal ileum. Enteric intussusception was diagnosed by characteristic Xray finding, so called "beak-like" filling defect in the terminal ileum. An exploratory laparotomy revealed focal subserosal thickening in the terminal ileum, and partial ileocolectomy was performed. Microscopically, we identified a pseudotumor that extended through the muscularis propria into serosa. The pseudotumor was composed of fibrous stroma and chronic inflammatory cells with calcification

Overexpression of a Minimal Domain of Calpastatin Suppresses IL-6 Production and Th17 Development via Reduced NF-κB and Increased STAT5 Signals

Calpain, a calcium-dependent cysteine protease, is reportedly involved in the pathophysiology of autoimmune diseases such as rheumatoid arthritis (RA). In addition, autoantibodies against calpastatin, a natural and specific inhibitor of calpain, are widely observed in RA. We previously reported that E-64-d, a membrane-permeable cysteine protease inhibitor, is effective in treating experimental arthritis. However, the exact role of the calpastatin-calpain balance in primary inflammatory cells remains unclear. Here we investigated the effect of calpain-specific inhibition by overexpressing a minimal functional domain of calpastatin in primary helper T (Th) cells, primary fibroblasts from RA patients, and fibroblast cell lines. We found that the calpastatin-calpain balance varied during Th1, Th2, and Th17 development, and that overexpression of a minimal domain of calpastatin (by retroviral gene transduction) or the inhibition of calpain by E-64-d suppressed the production of IL-6 and IL-17 by Th cells and the production of IL-6 by fibroblasts. These suppressions were associated with reductions in RORγt expression and STAT3 phosphorylation. Furthermore, inhibiting calpain by silencing its small regulatory subunit (CPNS) suppressed Th17 development. We also confirmed that overexpressing a minimal domain of calpastatin suppressed IL-6 by reducing NF-κB signaling via the stabilization of IκBα, without affecting the upstream signal. Moreover, our findings indicated that calpastatin overexpression suppressed IL-17 production by Th cells by up-regulating the STAT5 signal. Finally, overexpression of a minimal domain of calpastatin suppressed IL-6 production efficiently in primary fibroblasts derived from the RA synovium. These findings suggest that inhibiting calpain by overexpressing a minimal domain of calpastatin could coordinately suppress proinflammatory activities, not only those of Th cells but also of synovial fibroblasts. Thus, this strategy may prove viable as a candidate treatment for inflammatory diseases such as RA