microRNAs, short ribonucleic acid molecules which is typically 20-25 nucleotides long, can bind to complementary sequences in the three prime untranslated regions of target mRNAs, leading to the inhibition of translation or degradation of the mRNA. Theologically, human genome may have more than 1000 microRNAs, which target about 60% of human mRNAs. Thus, microRNAs have been implicated in the pathogenesis of various disorders. This paper discusses the present day understanding about the expression and role in various autoimmune diseases including rheumatoid arthritis, Sjogren syndrome, polymyositis/dermatomyositis, systemic lupus erythematosus, scleroderma, type I diabetis, and psoriasis. For example, the expression of miR-29, which targets type I collagen mRNA, is reported to be down-regulated in cultured dermal fibroblasts derived from scleroderma skin, contributing to excessive collagen production in this disease. Supplementation of the microRNA results in the decrease of collagen expression in scleroderma fibroblasts. In addition, serum miR-29a levels are significantly decreased in the very early stage of scleroderma. Investigation of the involvement of microRNAs in the pathogenesis of each autoimmune disease may lead to develop new biomarker and new therapeutic approach.

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  Several clinical trials revealed that leukocytapheresis (LCAP) was safe and effective therapy for patients with rheumatoid arthritis (RA). In this article, the mechanism of the efficiency of LCAP on RA is reviewed. The counts of activated CD4⁺ T cells and CD4⁺CD29⁺ T cells were significantly reduced in the synovial fluid after LCAP. Serum tumor necrosis factor alpha, interleukin (IL)-15 and RANTES were significantly reduced, while serum IL-10 significantly increased and this level increased significantly only in the responder group after treatment. P-glycoprotein (Pgp), which causes drug resistance by exclusion of intracellular drugs, expression on Th1 cells following LCAP therapy was significantly decreased after 4 sessions of treatment and 6 months after the last procedure in the responder group. Moreover, remarkable improvements of regulatory T cell (Treg) function were observed in good responders. Our findings suggest that LCAP may cause a reduction of activated T cells from affected joints, down-regulation of Pgp on helper T cells and restoration of Treg function, and that may modify the abnormal cytokine balance. These findings may explain some of the mechanisms by which the articular symptoms are improved by LCAP.

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  Prognosis of rheumatoid arthritis (RA) patients has significantly improved with the recent use of biologics targeting TNFα, IL-6, and co-stimulatory molecule. In US and Europe, clear therapeutic benefit of anti-CD20 antibodies is also confirmed. As a disease specific marker, rheumatoid factor and anti-citrullinated protein antibody are crucial in RA, although the pathology of them is not defined. Here we focus on glycolytic enzyme such as glucose-6-phospate isomerase, that is confirmed as arthritogenic in two different mouse models, and discuss about pathogenic relevance to RA.

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  Glucocorticoids (steroids) have been widely used for the treatment of patients with rheumatoid arthritis (RA) since Hench had attempted to administer cortisone (Kendall's compound E) to an active RA patient in 1948. Rheumatologists even in the 21st century can learn a lot from the history of steroid. In this feature article on steroid, a brief outline of 11β-hydroxysteroid dehydrogenase type 1, a tissue-specific regulator of steroid response, is presented. The isozyme re-activates inactive cortisone (compound E) to active cortisol (compound F), and seems to play an important role particularly in adipose tissue. In addition, I give an account of non-genomic mechanisms of steroid, which might be relevant to early and rapid effects during methylprednisolone pulse therapy. As for the field of practical rheumatology, rates and dosages of steroid administration for RA in Japan are shown, by looking into 3 large observational cohort researches and post-marketing surveillance programs for several biologics. The definition or an appropriate interpretation of medical/technical terms such as ‘effectiveness’ in the clinical setting and ‘low-dose’ steroid is also described.

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  Hemophilia A is an X-linked hereditary bleeding disorder caused by a congenital deficiency in blood coagulation factor VIII (FVIII). Therapy to prevent or treat bleeding is replacement of FVIII. The most significant complication of treatment in patients with hemophilia A is the development of alloantibodies that inhibit FVIII activity, termed inhibitors. In the presence of inhibitors, replacement of the missing clotting factor with FVIII preparations becomes less effective. Once replacement therapy is ineffective, morbidity increases. It remains unsolved to prevent inhibitor formation. The only strategy is long-term administration of a large quantity of FVIII in an attempt to eradicate the inhibitors through immune tolerance. However, little is known about the mechanisms involved in the induction of tolerance. This review will focus on the current understanding of why inhibitors develop and can be eradicated. The development of inhibitors by intravenous infusions of FVIII without adjuvant poses an intriguing challenge to immunologists.

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  Hemodialysis (HD) patients have been increasing recently. Some rheumatoid arthritis (RA) patients need hemodialysis (HD), though the proportion is not high. At present, such patients are almost treated with corticosteroids and/or nonsteroidal anti-inflammatory drugs alone, even if they have a high disease activity that would require disease-modifying anti-rheumatic drug (DMARD) therapy, partly because the safety of DMARDs in RA patients with end-stage renal disease has not been confirmed. Their joint destruction would be inevitable and lead to impaired activities of daily living. As there are no guidelines for the use of DMARDs in HD patients, here I reviewed the previous reports about the treatment of DMARDs including biologics for patients with RA undergoing HD.

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  Finding the means to ameliorate and prevent bone destruction as well as control inflammation is an urgent issue in the treatment of rheumatoid arthritis (RA). Recently, it has been demonstrated that osteoclastogenesis plays an important role in the bone destruction and pathogenesis of RA. Here, we review the effects of disease modifying anti-rheumatic drugs (DMRAD) on the amelioration of bone destruction and osteoclastogenesis.

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  In August 2010, a 73-year-old woman with rheumatoid arthritis receiving etanercept (ETN) therapy for two years, developed high-fever and abdominal fullness. Though she had not been exposed to tuberculosis, isoniazid prophylaxis was administrated. Antibiotics were not effective. CT images revealed the massive ascites and peritonitis, and Ga scintigraphy demonstrated notable uptake in the peritoneum. Ascites analysis showed an elevated adenosine deaminase activity value (104.9 IU/l) without malignant cells. Moreover, PCR and culture for Mycobacterium tuberculosis were positive. Finally, a diagnosis of tuberculous peritonitis was established. After initiating a standard anti-tuberculosis regimen with four drugs, her clinical condition ameliorated and ascites promptly regressed. Although the tuberculous peritonitis during ETN therapy is rare, this report emphasized the importance of initial suspicion of tuberculosis in these patients with tumor necrosis factor inhibitors such as ETN.

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  We report a 63-year-old man with a 35-year history of slowly progressive type 1 diabetes mellitus (SPIDDM), complicated with myeloperoxidase-specific anti-neutrophil cytoplasmic antibody (MPO-ANCA)-associated vasculitis presenting alveolar hemorrhage and pachymeningitis. The patient was first diagnosed as having DM at age of 28 years old and deteriorated secretion of insulin and the typical clinical course led us to the diagnosis of SPIDDM. When he was 58 years old, he suffered from fever, headache, and alveolar hemorrhage. He was diagnosed as having MPO-ANCA associated vasculitis based on a high titer of MPO-ANCA and histological findings of lung biopsy. Treatment with steroid pulse therapy, followed by oral prednisolone and oral cyclophosohamide, resulted in clinical improvement. Five years later, he complained of double vision. A gadolinium-enhanced magnetic resonance imaging (MRI) study of the brain showed normal. Two months later, he developed right cranial nerve V~XII palsy. A second MRI study revealed thickening of the right temporal region and cerebellar dura mater, leading us to the diagnosis of hypertrophic pachymeningitis. He responded well to oral prednisolone (50 mg/day) and intravenous cyclophosohamide (500 mg). This is the first case report of SPIDDM complicated with MPO-ANCA-associated vasculitis, manifesting as alveolar hemorrhage and hypertrophic pachymeningitis.

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