3 results on '"Hachiro Konaka"'
Search Results
2. Cell surface-expressed Ro52/IgG/HLA-DR complex is targeted by autoantibodies in patients with inflammatory myopathies
- Author
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Noriko Arase, Hideaki Tsuji, Hyota Takamatsu, Hui Jin, Hachiro Konaka, Yasuhito Hamaguchi, Kyoko Tonomura, Yorihisa Kotobuki, Ikuko Ueda-Hayakawa, Sumiko Matsuoka, Toru Hirano, Hideki Yorifuji, Hiroyuki Murota, Koichiro Ohmura, Ran Nakashima, Tomoharu Sato, Atsushi Kumanogoh, Ichiro Katayama, Hisashi Arase, and Manabu Fujimoto
- Subjects
Myositis ,Ribonucleoproteins ,Immunoglobulin G ,Immunology ,Humans ,Immunology and Allergy ,HLA-DR Antigens ,Autoantibodies ,Autoimmune Diseases - Abstract
Intracellular proteins are often targeted by autoantibodies in autoimmune diseases; however, the mechanism through which intracellular molecules are targeted remains unknown. We previously found that several intracellular misfolded proteins are transported to the cell surface by HLA class II molecules and are recognized by autoantibodies in some autoimmune diseases, such as rheumatoid arthritis, antiphospholipid syndrome, and microscopic polyangiitis. Ro52 is an intracellular Fc receptor that is a target antigen for myositis-associated autoantibodies. We analyzed the role of HLA class II molecules in the autoantibody recognition of Ro52. Ro52 alone was not transported to the cell surface by HLA class II molecules; however, it was transported to the cell surface in the presence of both IgG heavy chain and HLA class II molecules to form a Ro52/IgG/HLA-DR complex. The Ro52/IgG/HLA-DR complex was specifically recognized by autoantibodies from some patients with inflammatory myopathies. We then evaluated 120 patients with inflammatory myopathies with four types of myositis-specific antibodies and analyzed the autoantibodies against the Ro52/IgG/HLA-DR complex. The specific antibodies against the Ro52/IgG/HLA-DR complex were detected in 90% and 93% of patients who were positive for anti-MDA5 and anti-ARS antibodies, respectively. In individual patients with these two inflammatory myopathies, changes in serum titers of anti-Ro52/IgG/HLA-DR-specific antibodies were correlated with the levels of KL-6 (R = 0.51 in anti-MDA5 antibody-positive DM patients, R = 0.67 in anti-ARS antibody-positive PM/DM patients with respiratory symptoms) and CK (R = 0.63 in anti-ARS antibody-positive PM/DM patients with muscle symptoms) over time. These results suggest that antibodies against Ro52/IgG/HLA-DR expressed on the cell surface could be involved in the pathogenesis of inflammatory myopathy subgroups.
- Published
- 2022
3. Pathological and therapeutic implications of eosinophil-derived semaphorin 4D in eosinophilic chronic rhinosinusitis
- Author
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Yujiro Naito, Takayoshi Morita, Hyota Takamatsu, Yohei Maeda, Atsushi Kumanogoh, Yoshimitsu Nakanishi, Takeshi Nakatani, Yu Futami, Maiko Naito, Hidenori Inohara, Masaki Hayama, Daisuke Okuzaki, Hachiro Konaka, Takeshi Tsuda, Sho Obata, Masayuki Nishide, Yasuhiko Suga, Ayaka Nakatani, Yasuhiro Kato, Takashi Shikina, Yoshitomo Hayama, Kazuya Takeda, Shohei Koyama, Mayuko Izumi, Shingo Satoh, and Satoshi Nojima
- Subjects
Adult ,Male ,0301 basic medicine ,Immunology ,SEMA4D ,Semaphorins ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Antigens, CD ,Eosinophilia ,Eosinophilic ,medicine ,Animals ,Humans ,Immunology and Allergy ,Nasal polyps ,Sinusitis ,Rhinitis ,Mice, Inbred BALB C ,biology ,business.industry ,Transendothelial and Transepithelial Migration ,Middle Aged ,Eosinophil ,medicine.disease ,Recombinant Proteins ,Eosinophils ,Ovalbumin ,030104 developmental biology ,medicine.anatomical_structure ,Chronic Disease ,biology.protein ,Immunohistochemistry ,Female ,Nasal Lavage Fluid ,Antibody ,business ,hormones, hormone substitutes, and hormone antagonists ,030215 immunology - Abstract
Background Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis. Clinical markers for ECRS disease activity and treatment strategies have not been sufficiently established. Although semaphorins are originally identified as neuronal guidance factors, it is becoming clear that they play key roles in immune regulation and inflammatory diseases. Objective We sought to investigate the pathological functions and therapeutic potential of semaphorin 4D (SEMA4D) in ECRS. Methods Serum soluble SEMA4D levels in patients with paranasal sinus diseases were measured by ELISA. The expression of SEMA4D in blood cells and nasal polyp tissues was assessed by flow cytometry and immunohistochemistry, respectively. Generation of soluble SEMA4D was evaluated in matrix metalloproteinase-treated eosinophils. Endothelial cells were stimulated with recombinant SEMA4D, followed by eosinophil transendothelial migration assays. Allergic chronic rhinosinusitis was induced in mice using Aspergillus protease with ovalbumin. The efficacy of treatment with anti-SEMA4D antibody was evaluated histologically and by nasal lavage fluid analysis. Results Serum soluble SEMA4D levels were elevated in patients with ECRS and positively correlated with disease severity. Tissue-infiltrated eosinophils in nasal polyps from patients with ECRS stained strongly with anti-SEMA4D antibody. Cell surface expression of SEMA4D on eosinophils from patients with ECRS was reduced, which was due to matrix metalloproteinase-9–mediated cleavage of membrane SEMA4D. Soluble SEMA4D induced eosinophil transendothelial migration. Treatment with anti-SEMA4D antibody ameliorated eosinophilic infiltration in sinus tissues and nasal lavage fluid in the ECRS animal model. Conclusions Eosinophil-derived SEMA4D aggravates ECRS. Levels of serum SEMA4D reflect disease severity, and anti-SEMA4D antibody has therapeutic potential as a treatment for ECRS.
- Published
- 2020
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