Rheumatoid Arthritis: Suwa A

Suzuki Y, Wakabayashi T, Saito E, Yamada C, Suwa A. · Division of Rheumatology, Department of Internal Medicine, Tokai University School of Medicine. · Clin Calcium. · Pubmed #19252251 No free full text.

Abstract: More than 50 years have passed since glucocorticoid (GC) therapy was introduced into the treatment of rheumatoid arthritis (RA) . Although the effect of GC monotherapy on RA is limited to short-term and long-term GC treatment carries the risks of adverse effects and rebound phenomenon after the discontinuation, disease-modifying action of GC have been recently reported when used in combination with DMARDs. One of the important side effects associated with GC therapy is osteoporosis, and Japanese guidelines on the management and treatment of glucocorticoid -induced osteoporosis have been published recently. Further studies are necessary to elucidate long-term benefit-risk ratio of low-dose GC therapy on RA.

Suwa A, Saito E, Wakabayashi T, Suzuki Y. · Tokai University School of Medicine, Department of Internal Medicine, Division of Rheumatology, Japan. · Clin Calcium. · Pubmed #17660625 No free full text.

Abstract: Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic synovitis which causes osteoporosis and joint destruction. Recently, it has been well understood that pro-inflammatory cytokine plays a pivotal role in disease progression. These pro-inflammatory cytokine induces activation of osteoclasts, resulting in paraarticular osteoporosis and joint destruction. While systemic osteoporosis caused by several factors is often seen in patients with RA. This article reviews the pathologic condition of osteoporosis in RA.

Suzuki Y, Wakabayashi T, Saito E, Suwa A. · Tokai University School of Medicine, Department of Internal Medicine, Division of Rheumatology. · Clin Calcium. · Pubmed #17404484 No free full text.

Abstract: From the results of recent randomized controlled clinical trials of disease modifying antirheumatic drugs (DMARDs), slowing radiographic progression has been documented with the use of methotrexate, leflunomide, salazusulfapyridine, IM gold, and cyclosporine. Although the effects of DMARDs is inferior to that of anti-tumor necrosis factor (TNF) agents, DMARDs can stop the progression of joint damage with the achievement of remission or good response.

Kaneko Y, Suwa A, Ikeda Y, Hirakata M. · Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. · Mod Rheumatol. · Pubmed #16622722 No free full text.

Abstract: Low-dose methotrexate (MTX) therapy is widely used for rheumatoid arthritis (RA) because of its favorable efficacy and toxicity profile. Although Pneumocystis jiroveci pneumonia (PCP) is most often seen in severely immunosuppressed patients, PCP complicating low-dose MTX therapy for RA has been reported to sometimes occur. We herein report two cases of patients who developed PCP during treatment with low-dose MTX, and discuss the importance of prophylaxis for this opportunistic infection.

Matsudaira T, Tsuzuki S, Wada A, Suwa A, Kohsaka H, Tomida M, Ito Y. · Nano Medical Enginering Laboratory, RIKEN (The Institute of Physical and Chemical Research), Wako, Saitama, Japan. · Biotechnol Prog. · Pubmed #19194953 No free full text.

Abstract: Autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and autoimmune diabetes are characterized by the production of autoantibodies that serve as useful diagnostic markers, surrogate markers, and prognostic factors. We devised an in vitro system to detect these clinically pivotal autoantibodies using a photoimmobilized autoantigen microarray. Photoimmobilization was useful for preparing the autoantigen microarray, where autoantigens are covalently immobilized on a plate, because it does not require specific functional groups of the autoantigens and any organic material can be immobilized by a radical reaction induced by photoirradiation. Here, we prepared the microarray using a very convenient method. Aqueous solutions of each autoantigen were mixed with a polymer of poly(ethylene glycol) methacrylate and a photoreactive crosslinker, and the mixtures were microspotted on a plate and dried in air. Finally, the plate was irradiated with an ultraviolet lamp to obtain immobilization. In the assay, patient serum was added to the microarray plate. Antigen-specific IgG adsorbed on the microspotted autoantigen was detected by peroxidase-conjugated anti-IgG antibody. The chemical luminescence intensities of the substrate decomposed by the peroxidase were detected with a sensitive CCD camera. All autoantigens were immobilized stably by this method and used to screen antigen-specific IgG. In addition, the plate was covered with a polydimethylsiloxane sheet containing microchannels and automated measurement was carried out.

Takada T, Hirakata M, Suwa A, Kaneko Y, Kuwana M, Ishihara T, Ikeda Y. · Division of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. · Mod Rheumatol. · Pubmed #19089533 No free full text.

Abstract: To elucidate the clinical and histopathological features associated with autoantibodies to the signal recognition particle (SRP), we have studied 23 Japanese patients with this specificity among 3,500 patients with polymyositis/dermatomyositis and other connective tissue diseases. Anti-SRP antibodies were determined based on analysis of RNA and protein components by immunoprecipitation assays. The pathological analysis was performed by using special stainings including alkaline phosphatase, myosin ATPase, and modified Gomori trichrome stainings. Twenty-one (92%) of these 23 patients had myositis, 8 of whom (38%) required cytotoxic agents or intravenous immunoglobulin therapy in addition to corticosteroid therapy. Four patients (16%) had rheumatoid arthritis, two of whom had no features of myositis. Muscle biopsy specimens of 11 patients were examined histologically in detail. All 11 had muscle fiber necrosis and/or regeneration, but only one had infiltration of inflammatory cells. Six of the 11 (55%) patients showed type I fiber predominance by ATPase staining, while eight control myositis patients without anti-SRP antibodies did not. There was no correlation of other neurogenic features in histology with the presence of anti-SRP antibodies. These studies suggest that anti-SRP autoantibodies are most likely to be related to myopathies that are resistant to corticosteroid therapy and without inflammation histopathologically.

Suwa A, Hirakata M, Kaneko Y, Sato S, Suzuki Y, Kuwana M. · Department of Internal Medicine, Tokai University School of Medicine, 143 Shimokasuya, Isehara, Kanagawa 259-1193, Japan. · Clin Rheumatol. · Pubmed #19082529 No free full text.

Abstract: We describe a patient who presented with polymyositis with anti-Jo-1 antibodies at 18 years after the onset of rheumatoid arthritis and was successfully treated with the immunosuppressive drug mizoribine at the time of exacerbation. She had developed diabetes mellitus, cerebral infarction, and myocardial infarction after high-dose steroid therapy was initiated. Therefore, an immunosuppressant was preferred as the second-line agent. Treatment with 150 mg/day of mizoribine and 8 mg/day of prednisolone resulted in eventual normalization of muscle enzyme levels. Mizoribine is a purine antimetabolite that inhibits T cell activation/proliferation and B cell proliferation. The potential efficacy of mizoribine for polymyositis was suggested by this case.

Miyachi K, Matsushima H, Nakagawa Y, Murata K, Hawkins RW, Hirakata M, Suwa A, Adachi M, Yamasaki K, Fritzler MJ. · Health Sciences Research Institute, Inc., Yokohama 240-0005. · Rinsho Byori. · Pubmed #12884735 No free full text.

Abstract: An early endosome antigen previously reported by F.T. Mu could be stained on cytoplasmic vesicles of HEp-2 cells. Here, we have investigated autoantibodies against cytoplasmic vesicular antigens, especially against early endosome antigen 1. Twelve sera were selected on the basis of cytoplasmic vesicular staining patterns of HEp-2 cells. Protein-immunoprecipitation using 35S-methionine labeled HeLa lysates, and RNA immunoprecipitation using 32P-labeled HeLa lysates were conducted to characterize the cognate antigens. Nine of 12 sera reacted with proteins in the range of 162-180 kDa, three of which were found to react specifically with the 162 kDa 35S methionine labeled recombinant early endosome antigen 1. These proteins were not associated with common RNA. Although complete clinical information was not available, some of the patients had rheumatoid arthritis(RA). In addition, the RNA-IPP results suggest that other patients included one each with SLE, SSc, polymyositis, and Sjögren's syndrome. Anti-early endosome antigen 1 antibody was found in 25%(3 of 12) of sera known to stain cytoplasmic vesicles. The reactive sera came mostly from patients with RA. The sera was from one case each of clinical-confirmed RA, SLE and Sjögren's syndrome.

Fujii T, Nojima T, Yasuoka H, Satoh S, Nakamura K, Kuwana M, Suwa A, Hirakata M, Mimori T. · Section of Rheumatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo 160-8582, Japan. · Rheumatology (Oxford). · Pubmed #11752512 links to  free full text

Abstract: OBJECTIVE: To determine cytokines and MHC class II alleles in Japanese patients with adult Still's disease (ASD) and clarify the association between those profiles and chronic articular disease. METHODS: Of 35 patients with ASD (13 men, 22 women, mean age at onset 34.0 yr), 17 (49%) had chronic arthritis (>6 months, chronic articular ASD) and 18 (51%) lacked chronic arthritis (systemic ASD). Cytokines and cytokine receptors in sera were measured by ELISA. Correlations of each cytokine with disease activity or C-reactive protein (CRP) were determined. MHC class II alleles were examined by polymerase chain reaction methods. RESULTS: In chronic articular ASD, female gender was more frequent and liver dysfunction and myalgia were rarer than in systemic ASD. In active disease, the white blood cell count was lower, but total IgG was greater in patients with chronic articular ASD than in those with systemic ASD. Tumour necrosis factor (TNF) alpha, soluble TNF receptor 2 and interleukin (IL)-18 were increased in both types of ASD, even in remission. Soluble IL-2 receptors, IL-4 and IL-18 levels were correlated with disease activity or CRP value only in chronic articular ASD. Interferon gamma and IL-8 remained increased only in chronic articular ASD, even when disease activity, including IL-6 and CRP, was low. DRB1*1501 (DR2) and DRB1*1201 (DR5) alleles were more frequent in chronic articular than in systemic ASD, whereas DQB1*0602 (DQ1) was frequently observed in both types of ASD. CONCLUSION: The present study suggests that ASD with chronic articular disease has distinct clinical, cytokine and immunogenetic profiles.

Tanaka M, Nakajima A, Suwa A, Yamada T, Suzuki T, Inada S. · Divisin of Rheumatic Disease, Tokyo Metropolitan Ohtsuka Hospital. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #10771570 No free full text.

Abstract: We report a case with rheumatoid arthritis and hypersensitivity pneumonitis. A 66-year-old female was admitted to our hospital because of fever, cough, and progressive dyspnea on October 10, 1997. She had a history of rheumatoid arthritis from 1987 and was treated with cyclophosphamide when she developed pulmonary symptoms in September 1997. On admission arthritis was subsided. Fine crackles on ausculation of lung, hypoxia, ground-glass appearance on chest X-ray were detected. The computed tomography of the chest disclosed diffuse interstitial shadow with patchy destruction of alveolar structures. Bronchoalveolar lavage demonstrated an increase in lymphocytes with predominance of suppressor-cytotoxic T cell subset (CD 8+). The histopathological examination of transbronchial lung biopsy showed interstitial inflammation with marked predominance of lymphocyte with intraalveolar exudate. Her condition got better and she discharged without definitive diagnosis and treatment for her respiratory symptoms. Eight hours after she went back home, she suddenly presented high fever and cough and gradually developed dyspnea. She was readmitted 5 days after the previous discharge. Although no specific precipitin antibody against various microorganisms was detected in her sera, the diagnosis of hypersensitivity pneumonitis was made. Thirty mg per day of prednisolone was resolved her symptoms promptly. There was no reported case with hypersensitivity pneumonitis and rheumatoid arthritis of other collagen diseases. The clinical course that arthritis and pulmonary symptoms appeared alternatively is of considerable interest to investigate for the pathogenesis of these two immune disorders.

Suwa A, Hirakata M, Satoh S, Mimori T, Utsumi K, Inada S. · Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. · Clin Exp Rheumatol. · Pubmed #10410272 No free full text.

Abstract: Pneumonitis is one of the most serious adverse effects associated with low-dose weekly methotrexate (MTX) therapy. Immediate cessation of MTX, and the introduction of oxygen therapy and glucocorticoids usually results in a dramatic improvement in the pulmonary toxicity. We report here a case of MTX-induced pneumonitis in a patient with rheumatoid arthritis (RA). Severe hypoxemia and interstitial infiltration in both lung fields did not respond to the withdrawal of MTX and the administration of oxygen and steroid pulse therapy. When intravenous cyclophosphamide (CYC) pulse therapy was initiated, however, rapid physiologic and radiographic improvement was seen. Our case suggests that CYC treatment may have a beneficial effect on MTX-induced pneumonitis that is resistant to steroid therapy.