Japanese Journal of Clinical Immunology
Online ISSN : 1349-7413
Print ISSN : 0911-4300
ISSN-L : 0911-4300
Volume 32, Issue 1
Displaying 1-11 of 11 articles from this issue
The Memorial Thesis of the Best Poster Award in the 36th Annual Meeting of The Japan Society for Clinical Immunology
Review Articles
  • Kazuhisa NAKANO, Sho MATSUSHITA, Kazuyoshi SAITO, Kunihiro YAMAOKA, Yo ...
    2009 Volume 32 Issue 1 Pages 1-6
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      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.
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  • Toshimitsu FUJII, Mamoru WATANABE
    2009 Volume 32 Issue 1 Pages 7-14
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      FTY720 is a sphingosine-1-phosphate receptor modulator, which inhibits T-cell egress from lymph nodes, thereby prevents pathogenic T cells from migrating towards disease sites. In inflammatory bowel diseases, it is thought that colitogenic memory CD4+ T cells are intermittently reactivated in regional lymphoid organs, and return to inflammatory tissues. Little is known about how FTY720 controls the migration property of memory T cells and whether FTY720 could control the trafficking of T cells without the presence of lymphoid tissues. First, we here demonstrated that FTY720 prevents the development of colitis induced by the adoptive transfer of colitogenic lamina propria effector-memory CD4+ T (TEM) cells into SCID mice. Next, We demonstrated that FTY720 treatment suppresses the recirculation of CD4+ T cells in splenectomized lymphotoxin-α−/− mice that lack lymph nodes and spleen. Cell number of CD4+ T cells was markedly decreased in peripheral blood of FTY720-treated mice, but conversely increased in bone marrow. Notably, FTY720 treatment prevented the development of colitis induced by transfer of colitogenic TEM cells into SPX LT-a−/− x RAG-2−/− mice. Collectively, the present data indicate that FTY720 treatment may offer an additional role to direct trafficking of CD4+ T cells in BM, resulting in the prevention of memory T cell-mediated diseases including inflammatory bowel diseases.
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  • Asuka INOUE, Isao MATSUMOTO, Keiichi IWANAMI, Yoko TANAKA, Takayuki SU ...
    2009 Volume 32 Issue 1 Pages 15-19
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      Rheumatoid arthritis (RA) is a chronic inflammatory disease with a variable disease outcome, and is characterized with synovitis, erosive changes of the joints, pain and functional deficit. Etiology is unknown. In the pathogenesis of rheumatoid arthritis the key role have proinflammatory cytokines, particularly, tumour necrosis factor (TNFα). The prognosis of RA patients has improved significantly during recent years, after the introducion of TNFα-based therapy. Despite the wide use of these biologics, their precise mechanisms of action in RA remain unclear. In the K/BxN mice, glucose-6-phosphate isomerase (GPI) is an autoantigen recognized by T and B cells. Recombinant GPI immunization to DBA/1 mice also induced acute severe arthritis. This arthritis was clearly controlled by anti-TNFα Abs, suggesting similar etiology to RA. In this study, to understand the mechanisms of arthritis that was regulated by TNFα, we focused on TNFα-induced adipose-related protein (TIARP) in the generation of GPI-induced arthritis.
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  • Christian KLEMANN, Benjamin JE RAVENEY, Shinji OKI, Takashi YAMAMURA
    2009 Volume 32 Issue 1 Pages 20-28
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      For many years, CD4+ effector T cells were categorized into two subsets: T helper type 1 (Th1) and type 2 (Th2) cells. More recent research has refined this model, delineating further subsets; in particular, Th17 cells, activated CD4+ T cells characterised by the production of the cytokine IL-17. Autoantigen-specific Th17 cells are associated with pathology in a number of animal models of organ-specific autoimmune disease and evidence is mounting that Th17 cells are also critical in human autoimmunity.
      Retinoids, a family of compounds that bind to and activate retinoic acid receptors (RARs and RXRs), are able to alter CD4+ T cell differentiation in vitro though agonism and antagonism of a range of retinoid receptors. For example, all-trans retinoic acid (ATRA) inhibits Th17 differentiation and instead promotes the upregulation of Foxp3, a key transcription factor in regulatory T cells. Importantly, treatment with retinoids can modulate Th17-mediated autoimmunity: experimental autoimmune encephalomyelitis (EAE), the murine model of multiple sclerosis (MS), is ameliorated by ATRA administration due to suppression of both the differentiation and the function of Th17 cells. In this review, we discuss the unveiled molecular mechanism and the possible clinical application of retinoids for the treatment of human Th17-mediated autoimmune diseases.
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Review Articles
  • Yasuhito HAMAGUCHI
    2009 Volume 32 Issue 1 Pages 29-34
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      Anti-CD20 antibody immunotherapy effectively treats non-Hodgkin's lymphoma and autoimmune disease. However, the cellular and molecular pathways for B cell depletion remain undefined and the in vivo effect of immunotherapy on tissue B cells and their subsets is generally unknown. To identify the mechanisms for B cell depletion in vivo, a new mouse model for anti-CD20 immunotherapy was developed using a panel of twelve mouse anti-mouse CD20 monoclonal antibodies. Anti-CD20 antibodies rapidly depleted the vast majority of circulating and tissue B cells in an isotype-restricted manner that was completely dependent on effector cell Fc receptor expression. B cell depletion utilized FcγRI-, FcγRIII- and FcγRIV-dependent pathways, while B cells were not eliminated in FcR common γ chain-deficient mice. Monocytes were the dominant effector cells for B cell depletion, with no demonstrable role for T or NK cells. Although most anti-CD20 antibodies activated complement in vitro, B cell depletion was completely effective in mice with genetic deficiencies in C3 complement components. The considerable factors that determine the effectiveness of anti-CD20 immunotherapy are following: the expression level of CD20 on B cell surface; the dosage of anti-CD20 mAb; the association of Fcγ receptor with the isotype of the antibies; B cell subpopulations within different tissues. These findings have important clinical implications for anti-CD20 and other antibody-based therapies.
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  • Hiroaki TAMURA, Kiminori HASEGAWA
    2009 Volume 32 Issue 1 Pages 35-42
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      AA amyloidosis is a life threatening clinical complication of chronic inflammatory diseases such as rheumatoid arthritis. It has been demonstrated biochemically that amyloidosis resulted from abnormal folding of proteins, which are deposited as insoluble fibrils in extracellular tissue, leading to the disruption of their normal function. In this regard, amyloidosis has been recognized as a conformation disorder. Interestingly, genetic polymorphisms of amyloid precursor protein (SAA) have been reported to associate with increased risk for AA amyloidosis. Also recent biochemical research revealed that SAA is synthesized under the influence of the proinflammatory cytokines, such as IL-6, TNF-α, IL-1. Additionally, it was suggested that amyloid deposits in extracellurar tissue could reflect to the serum level of SAA in the reversible fashion, leading to the hypothesis that the control of the SAA synthesis could be beneficial to the treatment of amyloidosis. In this context, anti-cytokine therapies may be most effective. Especially the inhibition of IL-6 is critical to suppression of SAA production, so treatment with a humanized monoclonal antibody against human IL-6 receptor may not only ameliorate RA disease activity but also pave the way for the treatment of AA amyloidosis.
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  • Nobuko IIZUKA, Kazuki OKAMOTO, Syunsei HIROHATA, Tomohiro KATO
    2009 Volume 32 Issue 1 Pages 43-47
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      Analysis of autoantibodies/antigens has very important impact for investigation of the pathogenesis of autoimmune diseases, including systemic lupus erythematosus (SLE). Recent progress has enabled us to detect and analyze the autoantibodies/antigens easily by using a proteomics approach. By proteomics, we can directly detect proteins as gene products as well as their alterations by post-translational modification and internal abscission which are characteristically observed in proteins. For example, we pick up autoantigens of interest as spots through combination of two-dimensional electrophoresis and western blot, and identify them by analysis using mass spectrometry. These methods allow us to use clinical specimens, including various tissues as a source of autoantigens. In this review, we introduce application of proteomics approach to autoimmune diseases, referring to our study of the autoantigens detected by anti-neuronal antibodies in SLE patients with central nervous system involvement.
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Original Articles
  • Akito TSUTSUMI, Tetsuo KOBAYASHI, Satoshi ITO, Daisuke GOTO, Isao MATS ...
    2009 Volume 32 Issue 1 Pages 48-52
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      OBJECTIVE: Mannose binding lectin (MBL) is a key molecule in first line defense against various microorganisms. Polymorphism of the MBL gene greatly affects serum MBL concentration, and is known to be associated with occurrence of infectious diseases. We aimed to determine whether there is a relationship between occurrence or severity of chronic periodontitis (CP) and polymorphism of the MBL gene.
      PATIENTS AND METHODS: Ninety-eight CP patients and 63 healthy subjects with no periodontitis were typed for the codon 54 polymorphism of the MBL gene by PCR-restriction fragment length polymorphism method.
      RESULTS: Genotype frequencies of the codon 54 polymorphism were similar between patients and control subjects. When patients were categorized to mild, moderate and severe periodontits groups, possession of the low serum MBL concentration allele was a risk factor for having severe CP, as assessed by logistic regression analysis.
      CONCLUSION: Patients with MBL genotypes that cause lower serum MBL concentration may be at risk of having severe periodontitis. MBL gene typing may become useful to predict the prognosis of CP.
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  • Kumiko SHIMOYAMA, Noriyoshi OGAWA, Jin SAWADA, Osamu KIMOTO, Daisuke S ...
    2009 Volume 32 Issue 1 Pages 53-60
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      Minor salivary gland biopsy is useful for diagnosis of Sjögren's Syndrome, because it has 87.4% of sensitivity, 87.3% of specificity and 87.4% of accuracy. However, SS cannot be diagnosed solely on focus score (FS). Moreover, FS is at most semi-quantitative. We questioned 30 registered facilities of Society of Japan Sjögren's Syndrome about the method and evaluation of minor salivary gland biopsy. As a result, it turned out that there were no standard methods in the procedure of salivary gland biopsy. The small salivary gland can be reached easily with little invasive method, however there are several problems, which include ①necessity of a standard technique, ②minimization of the pain and ③establishment of proper evaluation system. It is thought that the establishment of a standard technique and evaluation method is necessary to minimize the pain and collect the sufficient amount of tissue. Here we report the analysis of the procedure of minor salivary gland biopsy performed in other institutions as well as in our hospital in order to propose a standardized procedure and evaluation system.
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Case Reports
  • Jo NISHINO, Kenichi KATO, Hideo YOSHIDA, Masao KATAYAMA, Shusaku FUKAY ...
    2009 Volume 32 Issue 1 Pages 61-65
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      Case 1 was a 46-year-old man who developed neck pain in addition to pain and swelling in the limb joints in 1975. The patient was diagnosed with ankylosing spondylitis (AS) in 1983 based on detection of sacroiliitis on X-ray as well as a positive result for HLA B-27. Following administration of non-steroidal anti-inflammatory drugs (NSAIDs) and sulfasalazine (SSZ), methotrexate (MTX) was substituted at doses up to 17.5 mg/week in addition to concomitant prednisolone (PSL) (7.5 mg/day). However, no favorable response was obtained. As pain and inflammatory response improved following initiation of infliximab (IFX) in April 2005, PSL was discontinued and MTX was reduced to 10 mg/week. Case 2 was a 57-year-old man who experienced limitation of neck mobility in 1975. The patient was diagnosed with AS in 1989 based on detection of cervical ankylosis and sacroiliitis on X-ray and was given NSAIDs. After developing pain and swelling in the limb joints in 1994, the patient was given PSL (10 mg/day), bucillamine, MTX (8 mg/week), and leflunomide but did not improve. Arthritis in the limbs showed short-term improvement following initiation of IFX in May 2005. These findings demonstrate that IFX is a treatment option for AS refractory to conventional treatment.
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  • Shuzo YOSHIDA, Tohru TAKEUCHI, Yasuo ITAMI, Kenichiro HATA, Koko WATAN ...
    2009 Volume 32 Issue 1 Pages 66-70
    Published: 2009
    Released on J-STAGE: February 28, 2009
    JOURNAL FREE ACCESS
      A 33-year-old woman presented with fever, malar rash, lymphadenopathy and pancytopenia 3 weeks after parturition. Serum C3 level was decreased and antinuclear antibody, anti-dsDNA antibody and anti-SS-A antibody were positive. Serum ferritin level was elevated (3454 ng/ml), and bone marrow aspirate revealed hemophagocytosis. She was diagnosed having systemic lupus erythematosus (SLE) associated with hemophagocytic syndrome (HPS). Oral prednisolone (55 mg/day) was initiated. Clinical manifestations and pancytopenia were improved and serum ferritin level was decreased. However, elevated anti-dsDNA antibody titer and reduced C3 level continued for a month after steroid therapy. The additional therapy of tacrolimus (3 mg/day) improved clinical and laboratory findings. This is a rare SLE case associated with HPS as primary manifestation after parturition.
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