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Yoshio Ozaki, Shosaku Nomura First Department of Internal Medicine, Kansai Medical University, Hirakata, JapanCorrespondence: Shosaku NomuraFirst Department of Internal Medicine, Kansai Medical University, 2-3-1 Shinmachi, Hirakata, Osaka, 573-1010, JapanTel +81 72 804 2754Fax +81 72 804 2041Email shosaku-n@mbp.ocn.ne.jpAbstract: The treatment of connective tissue disease (CTD) and CTD-related intractable diseases (CTD-IDs) currently depends on the use of steroid therapy. Approximately 20 years have passed since the approval of infliximab for rheumatoid arthritis in 2003. Since then, several biological therapeutics have been marketed and adapted for many CTDs and CTD-IDs other than rheumatoid arthritis. Although conventional treatment for patients with these diseases is rarely used because of their poor prognosis, these cases may benefit from biological therapeutics. However, choosing biological therapeutics is difficult because they have different target molecules compared with conventional therapeutics. In this review, we address the current situation of biological therapeutics for CTD-IDs including Behcet’s disease, psoriatic arthritis, ankylosing spondylitis, anti-neutrophil cytoplasmic antibody-related arthritis, and adult Still’s disease, as well as the choice of biological therapeutics in clinical practice.Keywords: connective tissue disease-related intractable disease, biological therapeutics, clinical practice, inflammatory cytokine

Saki Tsujimoto, Yoshio Ozaki, Tomoki Ito, Shosaku Nomura First Department of Internal Medicine, Kansai Medical University, Hirakata, Osaka, JapanCorrespondence: Shosaku NomuraFirst Department of Internal Medicine, Kansai Medical University, 2-3-1 Shin-Machi, Hirakata, Osaka 573-1191, JapanTel + 81 72 804 2754Fax + 81 72 804 2041Email shosaku-n@mbp.ocn.ne.jpBackground: Rheumatoid arthritis (RA) is characterized by systemic synovitis with bone erosion and joint cartilage degradation. Although the analysis of polymorphisms in cytokine-encoding genes is important or understanding the pathophysiology of RA and selecting appropriate treatment for it, few studies have examined such single-nucleotide polymorphisms (SNPs) specifically in Japanese patients. This study was established to investigate the associations between polymorphisms in cytokine-encoding genes, autoantibodies and therapeutic responses in Japanese RA patients.Methods: The subjects in this study consisted of 100 RA patients and 50 healthy controls. We extracted data on sex, age, disease duration, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and therapeutic responses, including to methotrexate (MTX) and biological disease-modifying antirheumatic drugs (DMARDs). Genomic DNA was isolated from peripheral blood, which was genotyped for IL-10, TNF-α, TGF-β1, and IFN-γ polymorphisms.Results: Regarding IL-10 (− 592 C/A and − 819 C/T), significant decreases in the frequencies of the IL-10 (− 592) CC genotype and (− 819) CC genotype were found in RA patients compared with the levels in controls. For IFN-γ (+874 T/A), a significant decrease in the frequency of the TT genotype was found in RA patients compared with that in controls. Regarding TGF-β1 (+869 T/C), patients with positivity for anti-CCP antibody had a significantly lower frequency of the CC genotype than those with negativity for it. Furthermore, the IL-10 (− 592) CC genotype and (− 819) CC genotype might be related to the biological DMARD-response.Conclusion: Our results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.Keywords: RA, SNP, cytokine gene polymorphism, anti-CCP antibody, biological DMARD

Kiyohiro Yamazaki,1 Yuta Yoshino,1 Kentaro Kawabe,1 Tomomasa Ibuki,1 Shinichiro Ochi,1 Yoko Mori,1 Yuki Ozaki,1 Shusuke Numata,2 Jun-ichi Iga,1 Tetsuro Ohmori,2 Shu-ichi Ueno1 1Department of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan; 2Department of Psychiatry, Course of Integrated Brain Sciences, Medical Informatics, Institute of Health Biosciences, the University of Tokushima Graduate School, Tokushima 770-8503, JapanCorrespondence: Jun-ichi IgaDepartment of Neuropsychiatry, Molecules and Function, Ehime University Graduate School of Medicine, Shitsukawa, Toon, Ehime 791-0295, JapanTel +81-89-960-5315Fax +81-89-960-5317Email iga.junichi.it@ehime-u.ac.jpIntroduction: Although ATP-binding cassette sub-family A member 7 gene (ABCA7) is known to be associated with Alzheimer’s disease, the relationship between ABCA7 and schizophrenia has been unknown.Methods: Schizophrenia patients (n = 50; 24 males, 62.1 ± 0.50 years old) and age- and sex-matched healthy controls (n = 50) were recruited for the mRNA analysis. Additionally, a case-control study for the rs3764650 genotypes was performed with 1308 samples (control subjects; n = 527, schizophrenia patients; n = 781). All participants were Japanese, unrelated to each other, and living in the same area.Results: The distributions of the rs3764650 genotypes in schizophrenia patients were not different from that of controls. However, the ABCA7 mRNA expression levels in schizophrenia patients were significantly higher than those in controls by a logistic regression analysis. Additionally, the ABCA7 mRNA expression levels in schizophrenia patients were correlated with the rs3764650 genotypes in a dose-dependent manner.Discussion: The ABCA7 mRNA expression levels in peripheral blood with the rs3764650 genotypes may be related to pathological mechanisms in schizophrenia and may be a biological marker for schizophrenia.Keywords: schizophrenia, ATP-binding cassette sub-family A member 7 gene, single nucleotide polymorphism, rs3764650, mRNA expression

Yuto Uchida,1 Daisuke Kato,1 Yoriko Yamashita,2 Yasuhiko Ozaki,3 Noriyuki Matsukawa1 1Department of Neurology, 2Department of Experimental Pathology, 3Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Abstract: Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of autoimmune encephalitis that can be paraneoplastic and usually responds to tumor resection and immunotherapy. More than 75% of patients with anti-NMDAR encephalitis fully recover or have only mild sequelae, whereas the remainder experience severe disability. It remains unknown why certain cases have refractory clinical disease courses. We report a case of anti-NMDAR encephalitis with bilateral ovarian teratomas who was refractory to tumor resection and early initiation of immunotherapy. During intensive care, immunohistochemical analyses of her cerebrospinal fluid showed persistently high reactivity of NMDAR antibody over time. Six months after the operation, pelvic computed tomography detected a recurrent ovarian teratoma. After total enucleation of the bilateral ovaries, with significant pathological findings of bilateral mature cystic teratomas, her clinical condition improved rapidly, paralleled by a decrease in anti-NMDAR reactivity. This case illustrates the need to keep considering why extensive treatment fails to influence the disease when we encounter patients with refractory anti-NMDAR encephalitis. Failure to improve after ovarian resection could be a marker of recurrent ovarian teratoma in anti-NMDAR encephalitis. Keywords: N-methyl-D-aspartate receptor, antibody, autoimmune encephalitis, refractory, recurrence