CD8+T-bet+ cells as a predominant biomarker for inclusion body myositis

Background

Myositis is a heterogeneous group of muscular auto-immune diseases with clinical and pathological criteria that allow the classification of patients into different sub-groups. Inclusion body myositis is the most frequent myositis above fifty years of age. Diagnosing inclusion body myositis requires expertise and is challenging. Little is known concerning the pathogenic mechanisms of this disease in which conventional suppressive-immune therapies are inefficacious.

可溶性TRAIL重组蛋白治疗CIA实验研究

用sTRAIL重组蛋白治疗CIA模型 ,探讨sTRAIL用于自身免疫病治疗的可能性。将鸡肋骨II型胶原蛋白注射大鼠 ,建立了RA的动物模型———胶原诱导性关节炎 ,自制的可溶性TRAIL蛋白治疗CIA ,观察治疗后关节炎指数与血清中炎性细胞因子的变化。结果是sTRAIL 30 0ng/只 (0 1ml/次 )局部应用于关节炎部位 ,皮下注射 1周以后 ,sTRAIL应用的大鼠症状较对照组指数评分稍有下降 ;患病大鼠较正常大鼠IFN γ和TNF α表达量增加 ,而经过sTRAIL治疗后两者表达量都有显著下降 (P <0 0 5 )。提示sTRAIL局部应用后可缓解关节炎的局部炎症 ,可能是通过抑制激活的淋巴细胞 ,减少炎症细胞因子的分泌量和对炎症细胞的趋化而起作用     

CD137 (ILA/4-1BB), expressed by primary human monocytes, induces monocyte activation and apoptosis of B lymphocytes

Human CD137 is a member of the tumor necrosis factor (TNF) receptor family and the homologue of murine 4-1BB. Recent studies have demonstrated that CD137 promotes accessory T cell activation, and regulates proliferation and survival of T lymphocytes. This study reports on the expression and function of CD137 in peripheral blood monocytes. While monocytes showed constitutive expression in 10 out of 18 healthy donors, CD137 was not expressed on resting T or B lymphocytes. Immobilized antibodies to CD137 markedly induced the production of IL-8 and TNF-alpha protein and mRNA, and led to inhibition of IL-10 expression by primary monocytes. Furthermore, cross-linking of CD137 on monocytes resulted in an increase of B lymphocyte apoptosis mediated by direct cell-cell contact of both cell populations. In conclusion, this study identified CD137 as a new receptor involved in monocyte activation by inducing a characteristic cytokine release profile. In addition, CD137 may play a role in monocyte-dependent control of B lymphocyte survival.     

Giant inflammatory polyposis of the descending colon associated with a Crohn's disease-like colitis

A case of giant inflammatory polyposis associated with a localized inflammatory bowel disease of the descending colon in a 49-year-old man is presented. Lower abdominal distension rapidly appeared without any previous history of gastrointestinal disease. Two months later, he underwent a left hemicolectomy. Postoperative recovery was complete and he remains in good health more than 2 years later. The resected colon showed a giant and bizarre polyposis measuring up to 12 cm in length and 2 cm in height and covering the entire circumference of the colon. The polyposis consisted of narrow worm- or noodle-like polyps that bridged over the irregularly shaped ulcers, which sometimes extended into muscularis propria. Although longitudinal ulcers or scars, stricture, and a cobble-stone appearance were not observed, transmural inflammation and deep fissures were found in the interpolypoid area. From these findings, this case seems to be more similar to Crohn's disease than other inflammatory bowel diseases.     

B-1 cells are pivotal for in vivo inflammatory giant cell formation

The mechanisms that govern giant cell (GC) formation in inflammatory, neoplastic and physiologic conditions are far from being understood. Here, we demonstrate that B-1 cells are essential for foreign-body GC formation in the mouse. GCs were analysed on the surface of glass cover slips implanted into the subcutaneous tissue of the animals. It was demonstrated that GCs are almost absent on cover slips implanted into the subcutaneous tissue of BALB/c or CBA/N X-linked immunodeficient mice. As these animals do not have B-1 cells in the peritoneal cavity, they were reconstituted with B-1 cells obtained from cultures of adherent mouse peritoneal cells. Results showed that in B-1-reconstituted animals, the number of GCs on the implant surface surpassed the values obtained with preparations from wild animals. In animals selectively irradiated (pleural and peritoneal cavities) to deplete these cavities of B-1 cells, GCs were also not formed. Enriched suspensions of B-1 cells grown in culture were labelled with [(3)H]-tymidine and injected into the peritoneal cavity of naive mice before implantation of glass cover slips. After 4 days, about 17% of mononuclear cells had their nuclei labelled, and almost 70% of GCs had one or more of their nuclei labelled when analysed by histoautoradiographic technique. A few GCs expressed an immunoglobulin M when analysed by immunostaining and confocal microscopy. Overall, these data demonstrate that B-1 cells are pivotal in the mechanisms of foreign-body GC formation in the mouse.     

Immunoglobulin leakiness in scid mice with CD4(+) T-cell-induced chronic colitis

Inflammatory bowel disease in scid mice is initiated by transplantation of CD4(+) T-cells from immunocompetent syngenic donor mice. As the disease progresses, immunoglobulin (Ig)-containing cells appear in the gut lamina propria, suggesting that locally accumulating Ig may play a role in disease development. In the present work we have investigated the relationship between disease progression and patterns or levels of Ig isotypes in the feces of scid mice suffering from an ongoing colitis. The data clearly showed that the severity or progression of the disease did not influence the levels of IgA, IgG1, IgG2a, IgG2b, and IgG3, whereas the level of fecal IgM increased during the course of colitis. The presence of the serum protein alpha-1-antitrypsin in fecal extracts from diseased mice suggests that some of the fecal Ig has leaked through the inflamed epithelial membrane into the gut lumen. Finally, Ig-containing cells were observed in mesenteric lymph nodes and in the spleen, suggesting that the fecal Ig is produced both systemically and locally in the gut wall. In conclusion, the present results demonstrate that the level of IgM increases as colitis progresses. Also, the five remaining major Ig isotypes are increased in the gut lumen of scid mice with colitis, but the individual Ig types vary randomly during the course of the disease. Thus, it is unlikely that immunoglobulins are involved in the immunopathogenesis of this model of colitis.     

Fecal microbiota transplantation for Clostridium difficile infection in Taiwan: Establishment and implementation

Clostridium difficile infection (CDI) remains a major public health issue, and fecal microbiota transplantation (FMT) has become one of the standard therapies for recurrent or refractory CDI. When compared to medical therapies, such as metronidazole or vancomycin, FMT has a high rate of treatment response with acceptable safety and efficiency. Following promulgation of the amendments in September 2018 in Taiwan, FMT has been indicated for recurrent or refractory CDI. The Taiwan Microbiota Consortium contributed to the Taiwan FMT Expert Consensus, which established basic norms and stipulated essential principles, including the indications for transplantation, eligible locations and personnel, donor screening policies, fecal sample handling, and post-FMT follow-up. However, establishing an eligible FMT team in a qualified hospital remains a clinical challenge, and the requirement for facilities and well-screened donors impedes the implementation of FMT. In this review, we aim to provide domestic FMT teams with explicit instructions to facilitate realization and increase the practice of FMT. Based on the Taiwan FMT Expert Consensus and current regulations, we performed a literature review and integrated the experiences of Taiwanese multidisciplinary experts into this article. The content intends to offer clinicians up-to-date evidence and highlight the essential points of FMT.     

HLA class II haplotypes associated with pulmonary interstitial lesions of polymyositis/dermatomyositis in Japanese patients

To elucidate the immunogenetic background of idiopathic inflammatory myopathies (IIM) such as polymyositis (PM), dermatomyositis (DM) and any overlapping subsets, with other collagen vascular diseases, HLA class I antigens and class II alleles were determined and compared from individuals with various clinical and serological features of IIM, including pulmonary interstitial lesions (PI). Seventy-three Japanese patients with myositis (32 PM, 18 DM, 23 overlapped subsets) and 62 healthy unrelated controls were enrolled onto the study. Statistical differences between groups were determined by the Fisher's exact probability test. Serum fluorescent antinuclear antibody, rheumatoid factor (RF), anti-SS-A/Ro antibody, anti-Jo1 antibody and anti-U1 RNP antibody were examined using routine methods. PI was detected by chest X-ray and/or computed tomography. In patients with DM, the frequency of the HLA-DRB1*1302-DQA1*0102-DQB1*0604 haplotype was significantly higher than in the healthy controls (42.1% vs 17.7%), and in the patients with PM (42.1% vs 9.4%). Furthermore, the frequency of the HLA-DRB1*0405-DQA1*03-DQB1*0401 haplotype was higher in the PM patients with PI than in the controls (50.0% vs 17.7%), and PM without PI (50.0% vs 5.5%). These results suggest that in terms of HLA class II association, Japanese DM and PM, and PM with and without PI, belong to different clinical groups.     

Bi-directional modulation of T cell-dependent antibody production by prostaglandin E(2).

T cell-dependent Ig production involves interaction between T cells and B cells. This study evaluated the effects of prostaglandin (PG) E(2) on Ig production in a system in which B cells were co-cultured with autologous CD4(+) T cell clones non-specifically activated by anti-CD3. The effects of PGE(2) on T cell-dependent Ig production differed substantially, depending on the T cells employed. We selected six T cell clones that were able to enhance Ig production (resistant T cell clones) and six T cell clones that inhibited Ig production in the presence of PGE(2) (sensitive T cell clones) for comparison. The resistant T cells produced high levels (>1000 pg/ml) of IL-2 and/or IL-4, and expressed high CD40L, OX40 and CD45RA, and low CD45RO. In contrast, sensitive T cells secreted low IL-2 (<500 pg/ml) and IL-4 (<200 pg/ml), and expressed low CD40, OX40 and CD45RA, and high CD45RO. Adding supernatant derived from resistant T cell clones restored Ig production inhibited by PGE(2), while removing IL-2, IL-4 or IL-10 using specific antibodies inhibited Ig production. In addition, we demonstrated a direct effect of PGE(2) on B cells to enhance Ig production. Consistently, in the presence of resistant T cells, PGE(2) increased B cell proliferation and differentiation. In conclusion, the effects of PGE(2) on Ig production consist of its indirect effects through T cells and its direct effects on B cells. The outcome of the effects can be up-regulatory or down-regulatory, depending whether resistant or sensitive T cells are involved.