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Volume 38 (2015)
- Issue 6 Pages 433-
- Issue 5 Pages 389-
- Issue 4 Pages 232-
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- Issue 2 Pages 79-
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Volume 38, Issue 5
Displaying 1-7 of 7 articles from this issue
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Erratum
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2015 Volume 38 Issue 5 Pages 389
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESS
Feature Articles
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Tomomitsu MIYAGAKI2015 Volume 38 Issue 5 Pages 390-397
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESSB cells have been generally considered to be positive regulators of immune responses because of their ability to produce antigen-specific antibodies and to activate T cells through antigen presentation. Impairment of B cell development and function may cause autoimmune diseases. Recently, specific B cell subsets that can negatively regulate immune responses have been described in mouse models of a wide variety of autoimmune diseases. The concept of those B cells, termed regulatory B cells, is now recognized as important in the murine immune system. Among several regulatory B cell subsets, IL-10-producing regulatory B cells are the most widely investigated. On the basis of discoveries from studies of such mice, human regulatory B cells that produce IL-10 in most cases are becoming an active area of research. There have been emerging data suggesting the importance of human regulatory B cells in various diseases. Revealing the immune regulation mechanisms of human regulatory B cells in human autoimmune diseases could lead to the development of novel B cell targeted therapies. This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in clinical research using human samples.View full abstractDownload PDF (854K) -
Shigeru IWATA, Yoshiya TANAKA2015 Volume 38 Issue 5 Pages 398-402
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESSB cells play a pivotal role in the pathogenesis of autoimmune diseases. In addition, B cells require interaction with helper CD4+ T cells to become activated. We assessed change of gene regulatory network that controls B cell differentiation after stimulation with BCR cross-linking, sCD40L, Toll-like Receptor (TLR) and cytokines such as IL-4/IL-21 in vitro. We found that combination with BCR, CD40 and TLR9 or IL-4/IL-21 signal via tyrosine kinases such as Syk/Btk/JAK caused robust gene expression of AICDA, BCL6, XBP1 and IgG production. We found that levels of Syk/Btk phosphorylation in B cells were preferentially higher in RA and SLE patients compared to healthy subjects. RA patients with higher p-Syk levels were significantly correlated to strongly positive for anti-citrullinated protein antibodies (ACPAs). Treatment with abatacept significantly reduced the levels of p-Syk in RA peripheral blood B cells, and also reduced the proportion of follicular helper T (Tfh) cells. We highlight tyrosine kinase such as Syk/Btk/JAK as potential targets for inhibiting B cell-T cell interactions in autoimmune diseases such as RA and SLE. We also state recent evidence of these drugs.View full abstractDownload PDF (1044K) -
Masakazu NAKAMURA, Manabu ARAKI, Takashi YAMAMURA2015 Volume 38 Issue 5 Pages 403-411
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESSMultiple sclerosis (MS) is an autoimmune disease targeting oligodendrocyte in the central nervous system and involves heterogeneous pathology that yields considerable nonresponders to the first line therapy interferon (IFN)-β. However, determinants for this clinical efficacy have not been elucidated. Interestingly, an MS-like autoimmune disease neuromyelitis optica (NMO) is exclusively resistant to this therapy and mediated by IL-6-dependnet PBs via producing a disease-specific autoantibody against aquaporin 4 (AQP4) on astrocyte. Therefore, we assumed that IFN-β-nonresponsive patients with MS may have the similar B-cell abnormality and found an expansion of circulating PBs in these nonresponders. In addition, these PBs exhibited an IL-6-dependent survival in vitro like those in NMO. Clinical features of such “PB-high” patients were consistent with antoantibody-mediated pathology. Thus, we are administering anti-IL-6 receptor blocking antibody tocilizumab to these intractable patients with MS to achieve precision medicine for MS.View full abstractDownload PDF (1654K) -
Hiroaki NIIRO2015 Volume 38 Issue 5 Pages 412-420
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESSThe advent of B-cell targeted agents has prompted reappraisal of the role of B cells in the pathogenesis of autoimmune diseases (AID). Most notably, pathogenic B cells not only are the source of antibodies but also function as potent effectors mainly via antigen presentation and costimulation, and release of pro-inflammatory cytokines. Along with recent findings showing the existence of regulatory B cells, the role of B cells in AID seems more complicated than previously thought. Autoreactive B cells normally remain innocuous by the multi-layered mechanisms of self-tolerance during ontogeny. Disruption of these mechanisms, however, leads to the development of AID, where pathogenic effector B cells are enriched in particular B cell subsets. Given risk/benefit considerations, a novel strategy to selectively target the function of effector B cells would be more preferable than the nonselective B-cell depletion achieved by anti-CD20 therapy in AID.View full abstractDownload PDF (1239K)
Case Reports
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Makoto KUBO, Kousuke UCHIDA, Tadaaki NAKASHIMA, Seiko ODA, Tomomi NAKA ...2015 Volume 38 Issue 5 Pages 421-425
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESSIn January 2009, a 62-year-old man presented with diarrhea, leg edema, and thrombopenia and was admitted to our hospital. The past medical history revealed Sjögren's syndrome and autoimmune hepatitis for which he had been administered prednisolone. On admission, a laboratory examination revealed massive hypoalbuminemia and high levels of C-reactive protein and platelet-associated IgG. Anti-double stranded DNA and anti-Sm antibodies were negative. Analysis of the bone marrow aspirate and Tc-99m albumin scintigraphy findings suggested autoimmune thrombocytopenic purpura (AITP) and protein-losing enteropathy (PLE), respectively. We diagnosed him as SLE, because past immunoserological testing had showed positivity for anti-double stranded DNA antibody and LE cells. Methylprednisolone pulse therapy and intravenous immunoglobulin therapy were ineffective. Rituximab was ineffective against PLE but was effective against AITP. Cyclosporine and Cyclophosphamide were ineffective against PLE. Subcutaneous injection of 200-μg octreotide daily and a medium chain triglyceride (MCT) diet was effective against PLE, and the patient's condition dramatically improved. The effectiveness of octreotide treatment and an MCT diet in the treatment of PLE with SLE is discussed.View full abstractDownload PDF (1040K) -
Mari KAMIYA, Makoto SOEJIMA, Hideyuki IWAI, Nobuyuki MIYASAKA, Hitoshi ...2015 Volume 38 Issue 5 Pages 426-431
Published: 2015
Released on J-STAGE: January 04, 2016
JOURNAL FREE ACCESSA 59-year-old man, who suffered from periodic fever with continuous elevation of the C-reactive protein (CRP) level was referred to our hospital. He had frequent respiratory infections and diarrhea since his childhood. The serum immunoglobulin (Ig) G level was low (537 mg/dl) while IgA and IgE were undetectable. The serum IgM level was elevated (737 mg/dl). Based on these clinical features, he was diagnosed with primary immune deficiency, hyper IgM syndrome. He had past histories of aortic aneurysm, which had been repaired surgically in his fifties. His persistent proteinuria made us to perform renal biopsy, which revealed nephrosclerotic changes. During the hospitalization, multiple events of subcortical brain hemorrhage, subarachnoid hemorrhage, and pulmonary alveolar hemorrhage occurred. Bleeding time and coagulation tests were normal. Antinuclear antibody, anti-neutrophil cytoplasmic antibody, or anti-cardiolipin antibody was absent. Herein, we described the first case of the immune deficiency associated with severe arteriosclerosis and hemorrhage.View full abstractDownload PDF (1909K)
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