Rheumatoid Arthritis: Japan

Koike R, Takeuchi T, Eguchi K, Miyasaka N, Anonymous00064. · Department of Pharmacovigilance, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. · Mod Rheumatol. · Pubmed #18084695 No free full text.

Abstract: Application of biological agents targeting tumor necrosis factor-alpha (TNF-alpha) caused a paradigm shift in the treatment of rheumatoid arthritis (RA). The introduction of infliximab in 2003 and etanercept in 2005 in Japan had a significant impact on both Japanese rheumatologists and RA patients, although serious adverse effects such as bacterial pneumonia, tuberculosis and Pneumocystis jiroveci pneumonia are significant concerns. Based on the data from post-marketing surveillance in Japan and accumulating evidence worldwide, the Internal Medicine Rheumatology Study Group of the Ministry of Health, Labor and Welfare (MHLW), Japan, has updated the guidelines for the use of anti-TNF-alpha agents for RA, which were subsequently approved by the Board of Japan College of Rheumatology (JCR). In the present revised guidelines, we combined the guidelines for use of each of infliximab and etanercept together with some modifications and precautions, paying special attention to serious adverse reactions. Although it is still controversial whether the use of TNF-alpha blocking agents per se increases the risk of infection or not, bacterial pneumonia, regardless of the pathogens, is the most frequent complications in RA. The risk factors associated with pneumonia identified in the post-marketing surveillance of infliximab in Japan are presented in this guideline. The diagnostic algorithm is also designed for early diagnosis and treatment of pulmonary lesions seen during the treatment of biological agents. Preventive measures and precautions against tuberculosis, another frequent and significant complication in Japan, are also described. Furthermore, risk factors for developing Pneumocystis pneumonia, which uniquely occurs at 30- to 50-fold frequency under TNF-alpha blockade therapy in Japan, are described here and its preventive measures are discussed. It is stressed that secondary-care rheumatologists should be better familiarized with the proper use of TNF-alpha blocking agents and be alert to any adverse events for a better management of RA patients.

Takayanagi H. · Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University. · Nippon Rinsho. · Pubmed #19432129 No free full text.

Abstract: The immune and skeletal systems share various molecules including cytokines, signaling molecules, transcription factors and membrane receptors, while immune cells are maintained in the bone marrow, which provides a physiological space for mutual interaction. In rheumatoid arthritis, synovium is the active site for the interplay between the immune and bone cells, the study of which accelerated the interdisciplinary field of osteoimmunology. This emerging field will be of great importance to better understand how antirheumatic drugs work and to develop new therapeutic strategies for rheumatic diseases.

Kotake S, Yago T, Nanke Y. · Institute of Rheumatology, Tokyo Women's Medical University. · Nippon Rinsho. · Pubmed #19432123 No free full text.

Abstract: Biologic therapies including tumor necrosis factor alpha (TNF-alpha)-blocking therapy have been shown to reduce disease activity measures and joint damage progression. However, effects of biologic therapies on systemic osteoporosis remain to be elucidated in patients with rheumatoid arthritis (RA). In this review article, we reviewed the literature on the issue after we described our hypothesis on the pathogenesis of synovitis in patients with RA.

Kobayashi M, Fukuda M, Nakayama J. · Department of Molecular Pathology, Shinshu University Graduate School of Medicine, Matsumoto, Japan. · Biol Pharm Bull. · Pubmed #19420741 links to  free full text

Abstract: Lymphocyte homing is mediated by a cascade of adhesive interactions between circulating lymphocytes and specialized endothelial cells comprising high endothelial venules (HEVs). Sulfated O-glycans expressed on HEVs, collectively called peripheral lymph node addressin (PNAd), interact with L-selectin expressed on lymphocytes, contributing to the initial step of the lymphocyte homing. In chronic inflammatory states, PNAd is induced on HEV-like vessels but absent in non-lymphoid tissues under normal conditions. Such HEV-like vessels have been observed in various chronic inflammatory diseases including rheumatoid arthritis, lymphocytic thyroiditis, Helicobacter pylori-associated chronic gastritis, and inflammatory bowel disease (IBD), and implicated in lymphocyte recruitment in those diseases. In H. pylori-associated chronic gastritis, PNAd-expressing HEV-like vessels are induced, and the progression of chronic inflammation is highly correlated with appearance of these vessels. Furthermore, eradication of H. pylori by antibiotics resulted in disappearance of PNAd. These results indicate that inhibition of PNAd formation could have therapeutic effect by attenuating lymphocyte recruitment. In ulcerative colitis (UC), PNAd-expressing HEV-like vessels are induced, preferentially in the active phase, and T cells, particularly CD4(+) T cells, are closely associated with these vessels, suggesting that T cell recruitment via PNAd-expressing HEV-like vessels plays at least a partial role in UC pathogenesis. Additionally, N-acetylglucosamine-6-O-sulfotransferase 1 (GlcNAc6ST-1) is suggested to be a candidate to regulate PNAd induction on HEV-like vessels in UC. These results provide a potential therapeutic strategy to treat UC by blocking T cell adhesion to PNAd-expressing HEV-like vessels. Inhibition or down-regulation of GlcNAc6ST-1 may be an alternative.

Mima T, Nishimoto N. · Laboratory of Immune Regulation, Wakayama Medical University, Wakayama City, Wakayama, Japan. · Curr Opin Rheumatol. · Pubmed #19365268 No free full text.

Abstract: PURPOSE OF REVIEW: Interleukin-6 (IL-6) is a multifunctional cytokine that regulates inflammatory response and immune reaction. Overproduction of IL-6 is pathologically involved in inflammatory autoimmune diseases such as rheumatoid arthritis (RA) and juvenile idiopathic arthritis, and therefore, blocking IL-6 activity is one of therapeutic options for these diseases. Tocilizumab is a humanized anti-IL-6 receptor (IL-6R) antibody and inhibits IL-6 activity. There is now accumulating evidence that tocilizumab is therapeutically effective for patients with RA and other inflammatory autoimmune diseases. This article reviews the clinical value of blocking IL-6R. RECENT FINDINGS: Tocilizumab, as monotherapy and in combination with methotrexate, has been shown to be effective for RA patients with insufficient efficacy to methotrexate or other disease-modifying antirheumatic drugs. These findings of tocilizumab have been expanded to patients refractory to tumor necrosis factor inhibitors. Tocilizumab also retards the progression of structural joint damage. Furthermore, a 5-year long-term safety and efficacy has been shown. Tocilizumab is also a promising therapeutic option for other rheumatic diseases such as systemic-onset juvenile idiopathic arthritis, adult-onset Still's disease, and Takayasu arteritis. SUMMARY: Blocking IL-6R with tocilizumab represents a promising new treatment for RA and other inflammatory diseases. Large registry data will warrant the safety profile of tocilizumab.

Kochi Y, Suzuki A, Yamada R, Yamamoto K. · University of Tokyo Hospital, Laboratory for Autoimmune Diseases, Center for Genomic Medicine, RIKEN, Tokyo, Japan. · J Autoimmun. · Pubmed #19324521 No free full text.

Abstract: A new age has begun in the genetics of rheumatoid arthritis (RA), as genome-wide association studies scanning the human genome have been put into practical use. Among the RA-susceptibility genes identified by genetic studies, HLA-DRB1 gene appears to represent the most major determinant of genetic predisposition to RA. However, inconsistent results of the contributions of non-HLA susceptibility genes have been described, with the exception of a few genes repeatedly associated with RA-susceptibility, such as PTPN22 gene in populations of European ancestry and PADI4 gene in populations of Asian ancestry, revealing the presence of genetic heterogeneity in RA. We review herein recent advances in the genetics of RA and discuss the underlying differences among populations of European and Asian ancestries, taking as examples our previous findings for RA-susceptibility genes in the Japanese population: PADI4; FCRL3; and CD244.

Mihara M, Ohsugi Y, Kishimoto T. · Product Research Department, Fuji-Gotemba Research Laboratories, Chugai Pharmaceutical Co. Ltd., Komakado 1-Chome, Gotemba-Shi, Shizuoka, Japan. · Biofactors. · Pubmed #19319845 No free full text.

Abstract: Deregulated production of interleukin-6 (IL-6) has been found in several chronic inflammatory autoimmune disorders, including rheumatoid arthritis (RA) and inflammatory bowel diseases. Treatment with tocilizumab, a humanized anti-human IL-6 receptor (IL-6R) antibody, significantly improved disease activity and inhibited the progression of joint destruction in RA patients, but the reason why IL-6 blockade causes improvement of RA is still unclear. In this review, we discuss the influence of anti-IL-6R antibody treatment on the differentiation of Th17 cells, which are thought to be involved in the pathogenesis of autoimmune diseases in animal models, present new results for the effect of anti-IL-6R antibody on the induction of Th17 cells in a mouse collagen-induced arthritis model, and come to the conclusion that anti-IL-6R antibody inhibited the differentiation of Th17 cells in mouse models. It is thought that this inhibitory action may contribute to the therapeutic effects of anti-IL-6R antibody in human autoimmune diseases.

Umehara H, Sawaki T, Kawanami T, Masaki Y, Fukushima T. · Division of Hematology and Immunology, Kanazawa Medical University. · Nippon Rinsho. · Pubmed #19280925 No free full text.

Abstract: Sjögren's syndrome (SS) is chronic autoimmune disease characterized by destructive lymphocyte infiltration of salivary and lacrimal glands, which results in dry eyes and dry mouth. Despite extensive study of the underlying cause of SS, the pathogenesis remains obscure. The Sjögren's International Collaborative Clinical Alliance (SICCA) by five Research Groups located in Argentina, China, Denmark, the United States and Japan, is the first registry and clinical data-specimen repository to establish the International Standard Criteria for diagnosing SS. Patients with SS have a relative increased risk for development of B cell lymphoma compared with other autoimmune rheumatic diseases. We discuss the possible mechanisms for lymphoma development. The topics concerning SS is IgG4-related lymphoproliferative diseases, such as Mikulicz's disease and autoimmune pancreatitis. Based on the analysis of patients registered from all over Japan, we propose a new clinical entity IgG4-positive multi-organ lymphoproliferative syndrome (IgG4+ MOLPS).

Hashimoto M, Sakaguchi S. · Department of Experimental Pathology, Institute for Frontier Medical Science, Kyoto University. · Nippon Rinsho. · Pubmed #19280920 No free full text.

Abstract: Connective tissue diseases (or systemic autoimmune diseases), such as rheumatoid arthritis or systemic lupus erythematosus, are characterized by B cell hyperactivity and production of various autoantibodies. T cells help B cell activation in the germinal center by enhancing somatic hypermutation and generation of high affinity pathogenic autoantibodies. Previously helper T cells were divided into Th-1 and Th-2 cells. Recently, Th-17 cells and regulatory T cells have been identified as distinct T cell lineages and their roles in inflammation or immune regulation are under intensive investigation. In this review, we discuss the contribution of each T cell subset to autoantibody production and systemic autoimmune diseases.

Kawahata K. · Department of Rheumatology and Allergy, Graduate School of Medicine, University of Tokyo. · Nippon Rinsho. · Pubmed #19280915 No free full text.

Abstract: Rheumatic diseases are suggested to be recognized 2400 years ago, but little progress had been made in distinguishing specific diseases until the 17th century. After the two decades, the concept of rheumatic diseases was established and followed by the new concept of autoimmune diseases in the 20th century. Many key drugs for rheumatic diseases, such as glucocorticoids and immunosuppressants, were developed in the 1940s and 1950s. Their effect, toxicity and limitations have been investigated for fifty years. On the other hand, new treatment strategy was developed. Advances in genetics and molecular cell biology in the 1980s brought us the discovery of many cytokines and chemokines and elucidated the role of these molecules in autoimmune diseases. These progresses have led to the development of a number of biological agents for the rheumatic diseases during past decade. Among these drugs, TNF blockade showed the remarkable effectiveness in rheumatoid arthritis and this success indicated the new treatment era. However, compared to the simplicity of target molecules in monoclonal antibody therapy, biological effects are more complex. Therefore, we must keep in mind the possibility of the appearance of unexpected adverse effects such as TGN1412. This review presents a history of rheumatology and discusses future directions of basic and clinical research for rheumatic diseases.

Imai K, Chiba T, Maeda G, Morikawa M. · Department of Biochemistry, School of Life Dentistry at Tokyo, The Nippon Dental University, 1-9-20 Fujimi, Chiyoda-ku, Tokyo 102-8159, Japan. · Mini Rev Med Chem. · Pubmed #19275724 No free full text.

Abstract: Rheumatoid arthritis (RA) is a systematic inflammatory and intractable disease, which progressively affects multiple joints. Recent findings strongly suggest a key role of WNT signaling in the disease initiation and progression. In this review, we discuss the role and possibility of treatment by targeting WNT signaling.

Nakano K, Matsushita S, Saito K, Yamaoka K, Tanaka Y. · The first dept. of Internal Medicine, University of Occupational & Environmental Health, Kitakyushu, Japan. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #19252371 links to  free full text

Abstract: The nerve systems affect immune functions by releasing neurotransmitters through lymphocyte cell-surface receptors. A major neurotransmitter dopamine transmits signals via five different seven-transmembrane G protein-coupled receptors termed D1 to D5. There is wide evidence for a decreased risk of rheumatoid arthritis (RA) in patients with schizophrenia which is associated with the excessive stimulation of D2-like receptors by dopamine. However, the reason for the negative association between RA and schizophrenia is unknown. We previously demonstrated that dendritic cells (DCs) could synthesize and store dopamine, DC released dopamine to naive CD4 T cells upon DC-T cell interaction and affected helper T-cell differentiation. Because DCs have been proposed to play a pivotal role in the initiation and perpetuation of RA by presentation of arthritogenic antigens to T cells, we here assessed effects and functions of dopamine on immune cells during the pathogenesis of RA. In this paper, we overview the series of our research findings, and present the possibility of drug discovery which target at dopamine receptors.

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.

Yukawa N, Mimori T. · Department of Rheumatology and Clinical Immunology, Graduate School of Medicine, Kyoto University. · Clin Calcium. · Pubmed #19252250 No free full text.

Abstract: Because of a paradigm shift in the therapeutic strategy of RA by biologics, the goal of RA therapy became not only the clinical remission, but also the imaging remission. From the results of randomized controlled clinical trials of disease modifying anti-rheumatic drugs (DMARDs), decreased radiographic progression has been documented. In particular, methotrexate (MTX) is described as "anchor drug" of RA therapy because inhibitory effects of MTX on radiographic progression are proved by many clinical trials. Although DMARDs can slow down the radiographic progression with the achievement of clinical remission in RA, some patients still have subclinical synovitis detected by imaging technique. Such subclinical inflammation may explain the observed discrepancy between disease activity and radiographic progression in RA during DMARD therapy.

Kadono Y, Tanaka S. · Orthopaedic Surgery, University of Tokyo Hospital. · Clin Calcium. · Pubmed #19252249 No free full text.

Abstract: We should consider not only controlling disease activity using DMARDs and biologics as a matter of course, but also preventing against joint destruction, in the treatment for rheumatoid arthritis. Although we can indirectly regulate bone erosion via controlling disease activity, the osteoclast-targeting therapy might be more effective to stop joint destruction. We are waiting for new drugs directly targeting osteoclasts, such as OPG which is the natural inhibitor of RANKL, or cathepsin K inhibitor which reduces degeneration of bone matrix.

Kotake S, Nanke Y, Yago T, Yamanaka H. · Institute of Rheumatology, Tokyo Women's Medical University. · Clin Calcium. · Pubmed #19252246 No free full text.

Abstract: Matrix metalloproteinase-3 (MMP-3) is a useful marker to evaluate the prognosis of joint destruction in rheumatoid arthritis (RA) . The role of MMP-3 in immune cells, however, remains to be elucidated in the pathogenesis of RA. On the other hand, biologic therapies, including tumor necrosis factor alpha (TNF-alpha) -blocking therapy, has been shown to reduce disease activity measures and joint damage progression ; however, the effects of biologic therapies on systemic osteoporosis remain to be elucidated in RA. In this article, we reviewed the literature on these issues after describing our hypothesis of the pathogenesis of synovitis in RA.

Ishiguro N. · Department of Orthopedic Surgery, Nagoya University School of Medicine. · Clin Calcium. · Pubmed #19252244 No free full text.

Abstract: Rheumatoid arthritis (RA) is a polyarticular joint disease. The inflammatory process is characterized by infiltration of inflammatory cells into the joints, leading to proliferation of synoviocytes and destruction of cartilage and bone. The Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases. It had been well recognized that MMP play major roles in the cartilage breakdown in RA and OA. Moreover ADAM-TS-1, -4, -5 have aggrecanase activity, and also involve the cartilage degradation in RA and OA. Of course they contribute the cartilage homeostasis in healthy subjects. Failure to regulate the synthesis, activation and inhibition of the proteinases finally leads to cartilage destruction. Aggrecan and type II collagen are major components in cartilage matrix. Cleavage of aggrecan by aggrecanase and that of collagen by collagenase are critical steps for degradation of articular cartilage in RA. To prevent the cartilage damage, inflammatory synovitis should be suppressed in early stage.

Inoue H, Takayanagi H. · Department of Cell Signaling, Graduate School, Tokyo Medical and Dental University. · Clin Calcium. · Pubmed #19252243 No free full text.

Abstract: In rheumatoid arthritis, T cells activation enhances osteoclast differentiation and bone destruction through receptor activator of NF-kappaB ligand (RANKL) . Recent study revealed the importance of interleukin-17 (IL-17) -producing helper T cell subset (Th17) in bone destruction. The emerging field of osteoimmunology will be of great importance not only to the better understanding of osteoclast differentiation and activation but also to the regulation of inflammation-associated bone destruction.

Sawai T, Uzuki M. · Division of Leading Pathophysiology, Department of Pathology, School of Medicine, Iwate Medical University. · Clin Calcium. · Pubmed #19252242 No free full text.

Abstract: Histopahological features of rheumatoid arthritis, beginning from synovitis through deteriorating cartilage and bone to joint destruction has basically unchanged since the old days. On the other hand many inflammatory factors initiating, sustaining and/or activating inflammation such as cytokines and proteolytic enzymes, were successively detected, and followed by genetic analysis using animal models such as transgenic and knockout methods. Newly developed therapies by biological products remarkably have influenced the inflammatory these factors and genes, and seemed to modify the histopathological features. This article refers the histopathlogical features of RA in topics such as places involved in early stage, and the cellular origin, especially about the fibroblast like cells (FLS) which have been paid attention recently as key cells presenting immunological, histiocytic and fibroblastic properties, furthermore, participating the bone destruction in part as well as osteoclast in RA. We also introduce the several animal models of RA applied by many researchers for therapeutic and genetic analyses in RA.

Kohsaka H. · Department of Medicine and Rheumatology, Graduate School, Tokyo Medical and Dental University. · Clin Calcium. · Pubmed #19252241 No free full text.

Abstract: It is supposed that autoaggressive T cell activation, triggered by unknown microorganisms, initiates inflammation in rheumatoid arthritis. It leads to activation of macrophages and synovial fibroblasts in the synovial tissues, which form a granulomatous pannus tissue. It becomes a platform of joint destruction activating osteoclastogenesis and release of cartilage-degrading enzymes. Biological reagents recently brought into the clinics are potently anti-rheumatic, and, in some cases, stop progression of the joint destruction and even repair the joint. It is now a realistic goal for next-generation anti-rheumatic treatments to inhibit joint destruction completely.

Kawabata K, Yamamoto K. · Division of Allergy and Rheumatology, Department of Medicine, University of Tokyo Hospital. · Clin Calcium. · Pubmed #19252239 No free full text.

Abstract: Rheumatoid arthritis is a chronic inflammatory polyarthritis and is thought to be an autoimmune, multifactorial and polygenic disease. Recent studies have uncovered many important players in the pathogenesis of rheumatoid arthritis. Immune cells, mesenchymal cells, and bone-associated cells are all involved in the pathogenesis and are closely related with each other. The genetic predisposition to rheumatoid arthritis is confirmed by many family studies and HLA association studies. Genome-wide disease association studies identified genetic risk foci, such as HLA-DRB1, PADI4, and PTPN22. In addition to the genetic contribution, environmental factors are increasingly recognized. Many studies revealed that smoking is a risk factor for rheumatoid arthritis. The role of B and T lymphocytes in the pathogenesis has been reevaluated by biological agents such as rituximab (anti-CD20 antibody) and abatacept (CTLA4-Ig) , respectively. T cells in rheumatoid arthritis have been shown to have the altered level of surface molecules such as CD28, cytokine pattern shift, and shortened telomere lengths. Moreover, telomere loss is recognized not only in lymphocytes but also in hematopoietic progenitor cells. This phenomenon and the presence of rheumatoid-specific anti-citrullinated protein antibodies are reported to be associated with HLA haplotypes.

Iwakura Y, Nakae S, Saijo S, Ishigame H. · Center for Experimental Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. · Immunol Rev. · Pubmed #19161416 No free full text.

Abstract: T-helper 17 (Th17) cells are a newly discovered CD4(+) helper T-cell subset that produces interleukin-17A (IL-17A) and IL-17F. IL-17A plays important roles in allergic responses such as delayed-type hypersensitivity, contact hypersensitivity, and allergic airway inflammation. IL-17A promotes inflammation by inducing various proinflammatory cytokines and chemokines, recruiting neutrophils, enhancing antibody production, and activating T cells. IL-17A expression is also augmented in autoimmune diseases such as multiple sclerosis and rheumatoid arthritis. Using mouse models of these diseases, we found that IL-17A plays a central role in their development. IL-6 is required for the development of Th17 cells and tumor necrosis factor functions downstream of IL-17A during the effector phase. IL-1 is important both for developing Th17 cells and eliciting inflammation. Th17 cells, like Th1 and Th2 cells, are involved in host defense against infections, but the contribution of these Th subsets to defense mechanisms differs among pathogens. The roles of IL-17F remain largely unknown. In this review, we introduce how IL-17A/IL-17F are involved in inflammatory immune responses and host defense mechanisms and discuss their relationship with other cytokines in the development of inflammatory and infectious diseases.

Takano H, Komuro I. · Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chiba, Japan. · Circ J. · Pubmed #19129679 links to  free full text

Abstract: Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor superfamily and form heterodimers with retinoid X receptor. Three PPAR isoforms have been isolated and termed alpha, beta (or delta) and gamma. Although PPARgamma is expressed predominantly in adipose tissue and associated with adipocyte differentiation and glucose homeostasis, PPARgamma is also present in a variety of cell types. Synthetic antidiabetic thiazolidinediones (TZDs) are well known as ligands and activators for PPARgamma. After it was reported that activation of PPARgamma suppressed production of pro-inflammatory cytokines in activated macrophages, medical interest in PPARgamma has grown and there has been a huge research effort. PPARgamma is currently known to be implicated in various human chronic diseases such as diabetes mellitus, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, and Alzheimer's disease. Many studies suggest that TZDs not only ameliorate insulin sensitivity, but also have pleiotropic effects on many tissues and cell types. Although activation of PPARgamma seems to have beneficial effects on cardiovascular diseases, the mechanisms by which PPARgamma ligands prevent their development are not fully understood. Recent data about the actions and its mechanisms of PPARgamma-dependent pathway in cardiovascular diseases are discussed here.

Sugita T. · Pharmacology Laboratory, Mitsubishi Tanabe Pharma Corporation, 1000 kamoshida-cho, Aoba-ku, Yokohama, Japan. · Yakugaku Zasshi. · Pubmed #19122432 links to  free full text

Abstract: TNFalpha (tumor necrosis factor-alpha) plays a critical role in the pathogenesis of inflammatory diseases including rheumatoid arthritis and Crohn's disease. Infliximab is a monoclonal antibody that recognizes human TNFalpha. Clinical trials have been persuasive that infliximab is effective and far superior to the conventional drug therapy in various inflammatory diseases. Combination of infliximab plus methotrexate is effective in patients with active rheumatoid arthritis who have not responded adequately to traditional disease-modifying anti-rheumatic drugs, and has produced significant improvement in clinical, radiographic, and functional outcomes. Infliximab is also an important treatment option in patients with active Crohn's disease who have not responded to conventional therapy and in those with this disease who have fistulae. Moreover, infliximab treatment has resulted in effective suppression of ankylosing spondylitis, psoriasis and ocular inflammation in patients with refractory uveoretinitis due to Behçet's disease. Thus, biologics targeting TNFalpha have revolutionized the therapy of inflammatory diseases. Here, the current status of clinical application of anti-TNFalpha biologics is reviewed by describing the clinical outcome of infliximab and future prospects of biologics are discussed.

Kumano K. · Pulmonary Medicine and Clinical Immunology, Dokkyo University School of Medicine. · Nihon Rinsho Meneki Gakkai Kaishi. · Pubmed #19122375 links to  free full text

Abstract: Human parvovirus B19 infection causes erythema infectiosum in child, aplastic crisis in patients with chronic hemolytic anemia, chronic pure red cell aplasia in immunocompromised patients and hydrops fetalis. Human parvovirus B19 causes arthritis and acute glomerulonephritis due to immunological mechanism. Other disorders, rheumatoid arthritis, vasculitis and thrombotic microangiopathy, are linked in human parvovirus B19 infection. Parvovirus B19 infection causes choronic rheumatoid-like arthropathy. Autoantibody and low complement were seen in acute human parvovirus infection, and parvovirus B19 infection present clinically lupus like tableau.