Interleukin-6 (IL-6) is a prototypical cytokine featuring pleiotropic and redundant activity. It is an essential factor to protect host from environmental stress and to maintain homeostasis, whereas its dysregulated, excessive or persistent production plays a pathological role in various inflammatory diseases. Then, IL-6 blockade was expected to become a novel therapeutic strategy and a humanized anti-IL-6 receptor antibody, tocilizumab was developed. Indeed, through clinical trials its efficacy and tolerable safety was proved and is now in clinical use for the treatment of chronic inflammatory diseases such as rheumatoid arthritis, juvenile idiopathic arthritis and Castleman's disease. Moreover, ongoing various clinical studies suggest that it will be widely applicable for the treatment of intractable chronic immune-mediated diseases as well as acute severe inflammatory diseases presenting with “cytokine storm”.

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  Recent advance in treatment of rheumatoid arthritis (RA) has been derived by biological disease-modifying antirheumatic drugs (bDMARDs) targeting cytokines. A Jak inhibitor tofacitinib, the first drug of targeted synthetic DMARD (tsDMARD), a novel category of DMARD, shows similar efficacy profile, but different safety concerns, compared to bDMARDs. It is, therefore, essential to understand the mode of action of tofacitinib in the context of safety and efficacy. We here document the possible mechanism of tofacitinib in patiens with RA, shedding light upon a characteristic adverse event, herpes zoster.

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  To accommodate the vast antigenic exposure from both food components and commensal bacteria, the gut has evolved a naturally anti-inflammatory environment. We have recently shown that lactic acid bacteria (LAB), a major population of small intestinal microbiota and often found in fermented foods, contain a large amount of double-stranded RNA and capable of inducing interferon-β (IFN-β) production from dendritic cells (DCs) via the Toll-like receptor 3 (TLR3) pathway. It is a significant feature of LAB and was not observed in other bacteria tested. Moreover, IFN-β secreted in response to LAB prevented experimental colitis. These results identify TLR3 as a sensor to small intestinal commensal bacteria and contribute to anti-inflammatory mechanism. We also show that oral administration of β-glucan enhance intestinal and systemic immune response in dectin-1-dependent manner. Thus elucidation of “gut to systemic immune-homeostasis” mediated by innate signals will be valued for the development of gut-biology and science-based food immunology, with a focus on innovation in the health and medical industries.

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Background: Thromboses and pregnancy morbidities are major pathologies of antiphospholipid syndrome (APS). In general, rheumatologists or hematologists see APS thrombosis patients, and they often give advices for the treatments of APS-related pregnancy morbidities, such as measurements and interpretations of antiphospholipid antibodies(aPL).
Objective: To survey the approaches of physicians in Japan to the diagnosis and treatment of aPL-associated pregnancy morbidities.
Method: The study group on the Health and Labour Sciences Research Grants sent a questionnaire to 550 board members of the Japan College of Rheumatology and the Japanese Society on Thrombosis and Hemostasis, and analyzed the responses.
Result: The number of valid responses was 157 (28.5%). The number of pregnant women who were diagnosed as having APS was 118.7 patients/year in 53 of 157 hospitals (33.8%). With respect to aPL measurements, 128 out of 157 hospitals (81.5%) determined one or more anticardiolipin antibodies or β₂GPI-dependent anticardiolipin antibodies with one or more lupus anticoagulants; however aPL tests of only 2 hospitals (1.3%) covered all aPLs defined in the classification criteria. The obstetricians were responsible for treatments in 33.1% to 42.3% of the hospitals. The treatment methods or duration of treatments did not reach to the general consensus.
Conclusion: The number of cases of aPL-related pregnancy complications that physicians have intervened was relatively small. There are considerable patients that are not diagnosed as having the disease due to insufficient aPL examinations. There were less involvement of physicians to the diagnosis and treatment of pregnant women with aPLs.

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Objective: To investigate clinical and laboratory features of giant cell arteritis (GCA).
Method: We included 24 patients (6 men, 18 women; mean age 69.8 years) in this study. GCA was diagnosed based on the American College of Rheumatology 1990 classification criteria.
Results: Mean serum C-reactive protein was 9.03 mg/dl. GCA was classified into three types: classic temporal arteritis type (cranial GCA, nine patients); large-vessel type, affecting the aorta and its major branches without temporal arteries (12 patients); generalized type, affecting both temporal arteries and large vessels (three patients). Swelling and tenderness of temporal arteries were recognized in temporal arteritis and generalized arteritis. Ten of these patients also had histopathologic findings of arteritis, including giant cells in biopsy specimens. Examination of HLA-class 1 expression showed that one patient with cranial GCA, three with generalized GCA, and seven with large-vessel GCA were positive for HLA-A24, and four patients with large-vessel GCA were positive for HLA-B39. One patient with cranial GCA, one with generalized GCA, and six with large-vessel GCA were positive for HLA-B52. Nine patients were positive for anti-phospholipid antibodies (seven for anti-cardiolipin antibody immunoglobulin G, seven for anti-cardiolipin β₂-glycoprotein-1 antibody, one for lupus anticoagulant).
Conclusion: Our study demonstrated that HLA-class 1 expression in GCA resembles that in Takayasu arteritis, suggesting that these two arteritis types share the same genetic background. In contrast, the difference in the prevalence of anti-phospholipid antibodies in GCA and Takayasu arteritis patients shows a difference in the characteristic aspects of these two arteritis types.

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  A 39-year-old man with seronegative rheumatoid arthritis which was refractory to methotrexate and prednisolone therapy complained of epigastralgia, melena and diarrhea. Diffuse mucosal damage was observed on endoscopic examination, and histological findings of the gastric and colonal mucosa showed AA type amyloidosis. He was diagnosed with ankylosing spondylitis (AS) on the basis of the clinical feature such as the limitation in range of motion of lumber spine, and sacroiliitis on MR imaging. Although digestive symptom ameliorated by fasting and antibiotic therapy, laboratory findings continued to reveal an elevation of serum C-reactive protein (CRP) value and arthritis worsened. However, after the initiation of the treatment with adalimumab (ADA), not only his manifestation but also serum levels of CRP became normalized promptly. As far as we could evaluated, follow-up colonoscopic examination showed normal mucosal findings and histologic examination proved that amyloid protein disappeared. Secondary gastrointestinal amyloidosis is ralely associated with AS. Therefore standard therapy is not established. This case might indicate an efficacy of ADA for secondary gastrointestinal amyloidosis accompanied with AS.

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