Tsuneyo Mimori

Publications (112)440.29 Total impact

• Article: Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis – Analysis Using More than 17,000 Assessments in the KURAMA Database

  Chikashi Terao mail, Motomu Hashimoto, Keiichi Yamamoto, Kosaku Murakami, Koichiro Ohmura, Ran Nakashima, Noriyuki Yamakawa, Hajime Yoshifuji, Naoichiro Yukawa, Daisuke Kawabata, Takashi Usui, Hiroyuki Yoshitomi, Moritoshi Furu, Ryo Yamada, Fumihiko Matsuda, Hiromu Ito, Takao Fujii, Tsuneyo Mimori
  [show abstract] [hide abstract]
  ABSTRACT: Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis.
  PLoS ONE 03/2013; 8(3):e59341. · 4.09 Impact Factor
• Article: The prognostic value of HRCT in myositis-associated interstitial lung disease.

  Kiminobu Tanizawa, Tomohiro Handa, Ran Nakashima, Takeshi Kubo, Yuji Hosono, Kensaku Aihara, Kohei Ikezoe, Kizuku Watanabe, Yoshio Taguchi, Kazuhiro Hatta, Toru Oga, Kazuo Chin, Sonoko Nagai, Tsuneyo Mimori, Michiaki Mishima
  [show abstract] [hide abstract]
  ABSTRACT: BACKGROUND: Polymyositis and dermatomyositis-associated interstitial lung disease (PM/DM-ILD) can have variable courses. We evaluated the prognostic value of high-resolution computed tomography (HRCT) in PM/DM-ILD. METHODS: The cases of 51 patients newly diagnosed with PM/DM-ILD were retrospectively reviewed. HRCT images at diagnosis were categorized into four radiological patterns based on the major findings and distributions of these abnormalities, and the disease extent on HRCT was scored. The impact of HRCT findings and other clinical parameters on day 90 and overall mortality were analyzed. RESULTS: Of the 51 patients (11 with polymyositis and 40 with dermatomyositis), the lower consolidation/ground-glass attenuation (GGA) pattern was observed in 21 patients (41%), lower reticulation was observed in 23 patients (45%), random GGA was observed in four patients (8%), and other patterns were observed in three patients (6%). Twenty-one patients (42%) were positive for anti-CADM-140. The lower consolidation/GGA pattern, clinically amyopathic dermatomyositis, fever (≥38.0 °C), ferritin levels >500 ng/mL, and the presence of anti-CADM-140 were significantly associated with 90-day mortality in univariate analysis. Multivariate analysis revealed that the lower consolidation/GGA pattern (odds ratio, 23.1; P = 0.02) and the presence of anti-CADM-140 (odds ratio, 14.1; P = 0.03) were independent predictors of 90-day mortality. This HRCT pattern was also associated with a higher 90-day morality rate among anti-CADM-140-positive patients. The lower consolidation/GGA pattern was also associated with overall mortality in univariate analysis, whereas only the presence of anti-CADM-140 was an independent determinant of overall mortality in multivariate analysis. CONCLUSION: HRCT patterns at diagnosis can help predict the prognosis of patients with PM/DM-ILD as well as the presence of anti-CADM-140.
  Respiratory medicine 02/2013; · 2.33 Impact Factor
• Article: Three Groups in the 28 Joints for Rheumatoid Arthritis Synovitis - Analysis Using More than 17,000 Assessments in the KURAMA Database.

  Chikashi Terao, Motomu Hashimoto, Keiichi Yamamoto, Kosaku Murakami, Koichiro Ohmura, Ran Nakashima, Noriyuki Yamakawa, Hajime Yoshifuji, Naoichiro Yukawa, Daisuke Kawabata, Takashi Usui, Hiroyuki Yoshitomi, Moritoshi Furu, Ryo Yamada, Fumihiko Matsuda, Hiromu Ito, Takao Fujii, Tsuneyo Mimori
  [show abstract] [hide abstract]
  ABSTRACT: Rheumatoid arthritis (RA) is a joint-destructive autoimmune disease. Three composite indices evaluating the same 28 joints are commonly used for the evaluation of RA activity. However, the relationship between, and the frequency of, the joint involvements are still not fully understood. Here, we obtained and analyzed 17,311 assessments for 28 joints in 1,314 patients with RA from 2005 to 2011 from electronic clinical chart templates stored in the KURAMA (Kyoto University Rheumatoid Arthritis Management Alliance) database. Affected rates for swelling and tenderness were assessed for each of the 28 joints and compared between two different sets of RA patients. Correlations of joint symptoms were analyzed for swellings and tenderness using kappa coefficient and eigen vectors by principal component analysis. As a result, we found that joint affected rates greatly varied from joint to joint both for tenderness and swelling for the two sets. Right wrist joint is the most affected joint of the 28 joints. Tenderness and swellings are well correlated in the same joints except for the shoulder joints. Patients with RA tended to demonstrate right-dominant joint involvement and joint destruction. We also found that RA synovitis could be classified into three categories of joints in the correlation analyses: large joints with wrist joints, PIP joints, and MCP joints. Clustering analysis based on distribution of synovitis revealed that patients with RA could be classified into six subgroups. We confirmed the symmetric joint involvement in RA. Our results suggested that RA synovitis can be classified into subgroups and that several different mechanisms may underlie the pathophysiology in RA synovitis.
  PLoS ONE 01/2013; 8(3):e59341. · 4.09 Impact Factor
• Article: Anti-MDA5 (melanoma differentiation-associated gene 5) antibody and dermatomyositis with rapidly progressive interstitial pneumonia.

  Ran Nakashima, Tsuneyo Mimori
  [show abstract] [hide abstract]
  ABSTRACT: Anti-MDA5 antibody is one of the dermatomyositis-specific autoantibodies and anti-MDA5-potsitive patients show characteristic clinical features, such as hypomyositis, high prevalence of acute/subacute interstitial pneumonia (A/SIP) with poor prognosis, hyperferritinemia and elevated hepatobiliary enzyme. We found that serum IL-6, IL-18, M-CSF and IL-10 were significantly higher and serum IL-12 and IL-22 were significantly lower in anti-MDA5-positive patients than in anti-MDA5-negative patients before treatment. Taking together these serological findings, we hypothesized that monocyte and macrophage activation may underlie in the pathophysiology of anti-MDA5-positive patients. They rarely survive after they become to need oxygenation, and so need to be treated as soon as possible once the diagnosis has been made. Intensive regimen of combined immunosuppressive therapy (high-dose corticosteroids, oral cyclosporin and intravenous cyclophosphamide (IVCY, 900-1000 mg/m(2) in every other week)) improved the survival rate of anti-MDA5-positive patients. Especially, the serum ferritin levels tended to go down about 14 days after IVCY, suggesting that IVCY might be a key drug in the treatment of anti-MDA5-positive A/SIP patients.
  Japanese Journal of Clinical Immunology 01/2013; 36(2):71-6.
• Article: Low Prevalence of Anti-DFS70/LEDGF Antibodies in Patients with Dermatomyositis and Other Systemic Autoimmune Rheumatic Diseases.

  Yoshinao Muro, Kazumitsu Sugiura, Ran Nakashima, Tsuneyo Mimori, Masashi Akiyama
  The Journal of Rheumatology 01/2013; 40(1):92-3. · 3.69 Impact Factor
• Article: Validation of different sets of criteria for the diagnosis of Sjögren's syndrome in Japanese patients.

  Hiroto Tsuboi, Shinya Hagiwara, Hiromitsu Asashima, Hisanori Umehara, Atsushi Kawakami, Hideki Nakamura, Hajime Sano, Kazuo Tsubota, Yoko Ogawa, Etsuko Takamura, Ichiro Saito, Hiroko Inoue, Seiji Nakamura, Masafumi Moriyama, Tsutomu Takeuchi, Yoshiya Tanaka, Shintaro Hirata, Tsuneyo Mimori, Isao Matsumoto, Takayuki Sumida
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  ABSTRACT: OBJECTIVE: To validate the revised Japanese Ministry of Health criteria for the diagnosis of Sjögren's syndrome (SS) (JPN) (1999), The American-European Consensus Group classification criteria for SS (AECG) (2002), and American College of Rheumatology classification criteria for SS (ACR) (2012). METHODS: The study subjects were 694 patients with SS or suspected SS who were followed-up in June 2012 at ten hospitals that form part of the Research Team for Autoimmune Diseases, The Research Program for Intractable Disease by the Ministry of Health, Labor and Welfare (MHLW). All patients had been checked for all four criteria of the JPN (pathology, oral, ocular, anti-SS-A/SS-B antibodies). We studied the clinical diagnosis made by the physician in charge and the satisfaction of the above criteria. RESULTS: Of the 694 patients, 499 patients did not have other connective tissue diseases (CTDs). SS was diagnosed in 476 patients (primary SS in 302, secondary SS in 174), whereas non-SS was diagnosed in 218 patients (without other CTDs in 197, with other CTDs in 21) by the physician in charge. The sensitivities of JPN, AECG, and ACR in the diagnosis of all forms of SS (both primary and secondary SS) were 79.6, 78.6, and 77.5 %, respectively, with respective specificities of 90.4, 90.4, and 83.5 %. The sensitivities of the same systems in the diagnosis of primary SS were 82.1, 83.1, and 79.1 %, respectively, with specificities of 90.9, 90.9, and 84.8 %, respectively. The sensitivities of the same systems in the diagnosis of secondary SS were 75.3, 70.7, and 74.7 %, respectively, with specificities of 85.7, 85.7, and 71.4 %, respectively. CONCLUSION: The sensitivity of JPN to all forms of SS and secondary SS, the sensitivity of AECG to primary SS, and the specificities of JPN and AECG for all forms of SS, primary SS, and secondary SS were highest in the diagnosis of SS in Japanese patients. These results indicate that the JPN criteria for the diagnosis of SS in Japanese patients are superior to ACR and AECG.
  Modern Rheumatology 12/2012; · 1.58 Impact Factor
• Article: PLD4 as a novel susceptibility gene for systemic sclerosis in a Japanese population.

  Chikashi Terao, Koichiro Ohmura, Yasushi Kawaguchi, Tetsuya Nishimoto, Aya Kawasaki, Kazuhiko Takehara, Hiroshi Furukawa, Yuta Kochi, Yuko Ota, Katsunori Ikari, Shinichi Sato, Shigeto Tohma, Ryo Yamada, Kazuhiko Yamamoto, Michiaki Kubo, Hisashi Yamanaka, Masataka Kuwana, Naoyuki Tsuchiya, Fumihiko Matsuda, Tsuneyo Mimori
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  ABSTRACT: BACKGROUND: Systemic sclerosis (SSc) is an autoimmune disease for which multiple susceptibility genes have been reported. Genome-wide association studies have shown that large numbers of susceptibility genes are shared among autoimmune diseases. Recently, we reported nine novel susceptibility genes for Japanese rheumatoid arthritis (RA). OBJECTIVE: To elucidate whether the 18 genes that displayed associations or suggestive associations for Japanese RA in our previous study are associated with SSc in Japanese. METHOD: We performed an association study involving 415 SSc patients and 16,891 controls, followed by a replication study, which involved 315 cases and 21,054 controls. The 18 markers were analyzed for their associations with SSc in the first study, and five markers were further analyzed in the replication study. The inverse-variance method was used to evaluate the associations of these markers with SSc in a combined study. RESULTS: Rs2841277 in the PLD4 gene displayed a significant association with SSc in Japanese patients (p=0.00017). We detected that rs2841280 in exon2 of PLD4 is in strong linkage disequilibrium with rs2841277 and introduces amino acid alteration. We also found associations between SSc and rs6932056 in TNFAIP3 and rs2280381 in IRF8 (p=0.0000095 and 0.0030), both of which displayed associations with SSc in a European population. CONCLUSIONS: We determined PLD4, phospholipase D4, as a novel susceptibility gene for SSc in Japanese, confirming the involvement of PLD4 in autoimmunity. Associations between SSc and TNFAIP3 or IRF8 were also detected in our Japanese population. SSc and RA seem to share relatively large proportions of their genetic backgrounds. © 2012 American College of Rheumatology.
  Arthritis & Rheumatism 11/2012; · 7.87 Impact Factor
• Article: [Rheumatoid arthritis: progress in diagnosis and treatment. Topics: II. Pathophysiology; 3. Autoantibodies in rheumatoid arthritis].

  Kosaku Murakami, Takao Fujii, Tsuneyo Mimori
  Nihon Naika Gakkai Zasshi 10/2012; 101(10):2844-50.
• Source

  Available from: Shigeki Momohara

  Article: Functional Variants in NFKBIE and RTKN2 Involved in Activation of the NF-κB Pathway Are Associated with Rheumatoid Arthritis in Japanese.

  Keiko Myouzen, Yuta Kochi, Yukinori Okada, Chikashi Terao, Akari Suzuki, Katsunori Ikari, Tatsuhiko Tsunoda, Atsushi Takahashi, Michiaki Kubo, Atsuo Taniguchi, Fumihiko Matsuda, Koichiro Ohmura, Shigeki Momohara, Tsuneyo Mimori, Hisashi Yamanaka, Naoyuki Kamatani, Ryo Yamada, Yusuke Nakamura, Kazuhiko Yamamoto
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  ABSTRACT: Rheumatoid arthritis is an autoimmune disease with a complex etiology, leading to inflammation of synovial tissue and joint destruction. Through a genome-wide association study (GWAS) and two replication studies in the Japanese population (7,907 cases and 35,362 controls), we identified two gene loci associated with rheumatoid arthritis susceptibility (NFKBIE at 6p21.1, rs2233434, odds ratio (OR) = 1.20, P = 1.3×10(-15); RTKN2 at 10q21.2, rs3125734, OR = 1.20, P = 4.6×10(-9)). In addition to two functional non-synonymous SNPs in NFKBIE, we identified candidate causal SNPs with regulatory potential in NFKBIE and RTKN2 gene regions by integrating in silico analysis using public genome databases and subsequent in vitro analysis. Both of these genes are known to regulate the NF-κB pathway, and the risk alleles of the genes were implicated in the enhancement of NF-κB activity in our analyses. These results suggest that the NF-κB pathway plays a role in pathogenesis and would be a rational target for treatment of rheumatoid arthritis.
  PLoS Genetics 09/2012; 8(9):e1002949. · 8.69 Impact Factor
• Article: A case of Behçet's disease developing after poststreptococcal acute glomerulonephritis.

  Yuichiro Kitai, Kosaku Murakami, Hajime Yoshifuji, Naoichiro Yukawa, Daisuke Kawabata, Koichiro Ohmura, Takao Fujii, Tsuneyo Mimori
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  ABSTRACT: We report a case of a 73-year-old Japanese male patient who developed Behçet's disease (BD) after poststreptococcal acute glomerulonephritis. Three months after the initial presentation, acneiform eruption and oral and genital ulcers appeared. Treatment with oral prednisolone (20 mg/day) resulted in the remarkable disappearance of these symptoms. These findings support the hypothesis that Streptococcus pyogenes may be an etiologic factor of BD.
  Modern Rheumatology 08/2012; · 1.58 Impact Factor
• Article: Living-donor lobar lung transplantation for rapidly progressive interstitial pneumonia associated with clinically amyopathic dermatomyositis: report of a case.

  Tsuyoshi Shoji, Toru Bando, Takuji Fujinaga, Fengshi Chen, Hajime Sasano, Naoichiro Yukawa, Tsuneyo Mimori, Hiroshi Date
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  ABSTRACT: Diffuse interstitial pneumonia (IP) associated with collagen disease is a rare indication for lung transplantation. The manifestations of collagen disease are variable and dermatomyositis (DM) is often considered a contraindication for lung transplantation because of active myositis and a high incidence of malignancy. Furthermore, clinically amyopathic dermatomyositis (C-ADM) is associated with rapidly progressive IP resulting in a poor prognosis. Bilateral living-donor lobar lung was transplanted in a 52-year-old female with rapidly progressive IP associated with C-ADM, and the postoperative course was uneventful. To our knowledge, this case represents the first living-donor lobar lung transplantation for a patient with rapidly progressive IP associated with C-ADM.
  General Thoracic and Cardiovascular Surgery 05/2012;
• Article: Serum BAFF and APRIL levels in patients with IgG4-related disease and their clinical significance.

  Kazuhiro Kiyama, Daisuke Kawabata, Yuji Hosono, Koji Kitagori, Naoichiro Yukawa, Hajime Yoshifuji, Koichiro Omura, Takao Fujii, Tsuneyo Mimori
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  ABSTRACT: B cell-activating factor of the tumor necrosis factor family (BAFF) and a proliferation-inducing ligand (APRIL) play a crucial role in B cell development, survival, and antibody production. Here we analyzed the serum levels of BAFF and APRIL and their respective clinical associations in patients with an immunoglobulin (Ig) G4-related disease (IgG4-RD). We measured serum levels of BAFF and APRIL in patients with IgG4-RD, primary Sjögren's syndrome (pSS), and healthy individuals. Serum BAFF and APRIL levels in IgG4-RD were assessed for correlations with serological parameters, including Ig, particularly IgG4, and the number of affected organs. Serum BAFF and APRIL levels in IgG4-RD were monitored during glucocorticoid (GC) therapy. Serum BAFF and APRIL levels in patients with IgG4-RD were significantly higher (P < 0.01) than in healthy individuals. The BAFF levels of patients with IgG4-RD were comparable to those of patients with pSS. Although clinical parameters, such as serum IgG4 and the number of affected organs, were not correlated with the levels of BAFF, serum APRIL levels were inversely correlated with serum IgG4 levels (r = -0.626, P < 0.05). While serum BAFF levels decreased following GC therapy, serum APRIL levels increased during follow-up. These results indicate that BAFF and APRIL might be useful markers for predicting disease activity in IgG4-RD. Further studies are needed to elucidate the role of BAFF and APRIL in the pathogenesis of IgG4-RD.
  Arthritis research & therapy 04/2012; 14(2):R86. · 4.27 Impact Factor
• Article: Meta-analysis identifies nine new loci associated with rheumatoid arthritis in the Japanese population.

  Yukinori Okada, Chikashi Terao, Katsunori Ikari, Yuta Kochi, Koichiro Ohmura, Akari Suzuki, Takahisa Kawaguchi, Eli A Stahl, Fina A S Kurreeman, Nao Nishida, [......], Michiaki Kubo, Yusuke Nakamura, Naoyuki Kamatani, Tsuneyo Mimori, Robert M Plenge, Hisashi Yamanaka, Shigeki Momohara, Ryo Yamada, Fumihiko Matsuda, Kazuhiko Yamamoto
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  ABSTRACT: Rheumatoid arthritis is a common autoimmune disease characterized by chronic inflammation. We report a meta-analysis of genome-wide association studies (GWAS) in a Japanese population including 4,074 individuals with rheumatoid arthritis (cases) and 16,891 controls, followed by a replication in 5,277 rheumatoid arthritis cases and 21,684 controls. Our study identified nine loci newly associated with rheumatoid arthritis at a threshold of P < 5.0 × 10(-8), including B3GNT2, ANXA3, CSF2, CD83, NFKBIE, ARID5B, PDE2A-ARAP1, PLD4 and PTPN2. ANXA3 was also associated with susceptibility to systemic lupus erythematosus (P = 0.0040), and B3GNT2 and ARID5B were associated with Graves' disease (P = 3.5 × 10(-4) and 2.9 × 10(-4), respectively). We conducted a multi-ancestry comparative analysis with a previous meta-analysis in individuals of European descent (5,539 rheumatoid arthritis cases and 20,169 controls). This provided evidence of shared genetic risks of rheumatoid arthritis between the populations.
  Nature Genetics 03/2012; 44(5):511-6. · 35.53 Impact Factor
• Article: Interstitial lung disease in myositis: clinical subsets, biomarkers, and treatment.

  Tsuneyo Mimori, Ran Nakashima, Yuji Hosono
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  ABSTRACT: Interstitial lung disease (ILD) is the most frequent organ involvement (found in nearly half) of myositis patients, but it reveals various clinical courses and therapeutic responsiveness according to clinical and serological subsets. Autoantibodies, as well as imaging and histopathological studies, are useful for the classification of ILD in myositis and provide useful information for predicting prognosis and determining treatment. Antisynthetase antibodies are correlated with chronic and recurrent ILD, whereas anti-CADM-140 (MDA5/IFIH1) antibodies are a marker of acute progressive ILD in clinically amyopathic dermatomyositis. Serum KL-6, SP-D, and ferritin are useful biomarkers for monitoring the activity and severity of ILD. Regarding treatment, glucocorticoids are the first-line drug, but additional immunomodulating drugs are also used in refractory patients. Cyclophosphamide and calcineurin inhibitors (cyclosporine and tacrolimus) appear to be the key drugs in the treatment of refractory myositis-ILD. Rituximab may become another candidate if these drugs are not effective.
  Current Rheumatology Reports 02/2012; 14(3):264-74.
• Article: Follistatin-related protein/follistatin-like 1 evokes an innate immune response via CD14 and toll-like receptor 4.

  Kosaku Murakami, Masao Tanaka, Takashi Usui, Daisuke Kawabata, Aoi Shiomi, Mikiko Iguchi-Hashimoto, Masakazu Shimizu, Naoichiro Yukawa, Hajime Yoshifuji, Takaki Nojima, Koichiro Ohmura, Takao Fujii, Hisanori Umehara, Tsuneyo Mimori
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  ABSTRACT: Follistatin-related protein (FRP)/follistatin-like 1 (FSTL1) has multi-specific binding nature especially with TGF-β superfamily proteins, and thereby modulates organ development. However, its function in immune systems remains unclear. Previously, we reported FRP interacts with CD14, which is known to mediate toll-like receptor 4 (TLR4) signaling. Here, we investigated whether FRP activates TLR4 signaling. Recombinant FRP induced interleukin 6 or interleukin 8 production from target cells in a CD14- and TLR4-dependent manner. Moreover, similar to lipopolysaccharide (LPS), FRP induced tolerance to the second LPS stimulation. FRP has the function of evoking innate immune responses as one of the endogenous TLR4 agonists.
  FEBS letters 02/2012; 586(4):319-24. · 3.54 Impact Factor
• Article: [The cutting-edge of medicine: progress of autoantibodies in polymyositis and dermatomyositis-biomarker for myositis-associated interstitial lung disease].

  Tsuneyo Mimori, Yuji Hosono, Ran Nakashima
  Nihon Naika Gakkai Zasshi 02/2012; 101(2):488-94.
• Article: NEFA/nucleobindin-2 is a target autoantigen of the anti-Wa antibody and is associated with transfer RNA.

  Yoshitaka Imura, Yuichiro Shirai, Takaki Nojima, Ran Nakashima, Hajime Yamagata, Kiyomitsu Miyachi, Hajime Yoshifuji, Daisuke Kawabata, Koichiro Ohmura, Takashi Usui, Takao Fujii, Tsuneyo Mimori
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  ABSTRACT: The anti-Wa antibody found in systemic sclerosis patients reacts with a transfer RNA (tRNA)-associated 48-kDa protein and immunoprecipitates several tRNAs. We investigated the Wa antigen and its binding to tRNA species. We performed molecular cloning of the Wa antigen and made its recombinant protein. To investigate Wa antigen distribution in the cell, we performed an indirect immunofluorescence study. To determine the Wa-bound tRNA species, we performed a reverse transcription (RT)-polymerase chain reaction (PCR) using the RNAs immunoprecipitated by anti-Wa antibody as templates, and synthetic primers of mammalian tRNA sequences. To clarify the tissue expression of Wa antigen, we performed quantitative and semi-quantitative PCR of the cDNA. We demonstrated that the Wa antigen was identical to NEFA (DNA binding/EF-hand/acidic amino acid rich region), otherwise known as nucleobindin-2. A full-length and an alternative splice variant cDNA lacking exon 11 were isolated by cloning NEFA cDNA. Anti-Wa-positive sera stained both the nucleus and cytoplasm of HEp-2 cells. RT-PCR suggested that Wa binds at least six tRNA species. In human tissues, NEFA is expressed predominantly in exocrine glands. We have demonstrated that the Wa antigen is NEFA or nucleobindin-2, which binds specific tRNA species, and is distributed in specific human tissues.
  Modern Rheumatology 01/2012; 22(5):685-94. · 1.58 Impact Factor
• Article: Quantitative effect of HLA-DRB1 alleles to ACPA levels in Japanese rheumatoid arthritis: no strong genetic impact of shared epitope to ACPA levels after stratification of HLA-DRB1*09:01.

  Chikashi Terao, Katsunori Ikari, Koichiro Ohmura, Taku Suzuki, Takuji Iwamoto, Kiyoshi Takasugi, Hiroo Saji, Atsuo Taniguchi, Shigeki Momohara, Hisashi Yamanaka, Fumihiko Matsuda, Tsuneyo Mimori
  Annals of the rheumatic diseases 01/2012; 71(6):1095-7. · 8.11 Impact Factor
• Source

  Available from: Hisanori Umehara

  Article: Comprehensive diagnostic criteria for IgG4-related disease (IgG4-RD), 2011.

  Hisanori Umehara, Kazuichi Okazaki, Yasufumi Masaki, Mitsuhiro Kawano, Motohisa Yamamoto, Takako Saeki, Shoko Matsui, Tadashi Yoshino, Shigeo Nakamura, Shigeyuki Kawa, [......], Kenji Notohara, Takayuki Sumida, Yoshiya Tanaka, Tsuneyo Mimori, Tsutomu Chiba, Michiaki Mishima, Toshifumi Hibi, Hirohito Tsubouchi, Kazuo Inui, Hirotaka Ohara
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  ABSTRACT: IgG4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4+ plasma cells. Although IgG4-RD is not rare and is clinically important, its clinical diagnostic criteria have not been established. Comprehensive diagnostic criteria for IgG4-RD, including the involvement of various organs, are intended for the practical use of general physicians and nonspecialists. Two IgG4-RD study groups, the Umehara and Okazaki teams, were organized by the Ministry of Health, Labor and Welfare Japan. As IgG4-RD comprises a wide variety of diseases, these groups consist of physicians and researchers in various disciplines, including rheumatology, hematology, gastroenterology, nephrology, pulmonology, ophthalmology, odontology, pathology, statistics, and basic and molecular immunology throughout Japan, with 66 and 56 members of the Umehara and Okazaki teams, respectively. Collaborations of the two study groups involved detailed analyses of clinical symptoms, laboratory results, and biopsy specimens of patients with IgG4-RD, resulting in the establishment of comprehensive diagnostic criteria for IgG4-RD. Although many patients with IgG4-RD have lesions in several organs, either synchronously or metachronously, and the pathological features of each organ differ, consensus has been reached on two diagnostic criteria for IgG4RD: (1) serum IgG4 concentration >135 mg/dl, and (2) >40% of IgG+ plasma cells being IgG4+ and >10 cells/high powered field of biopsy sample. Although the comprehensive diagnostic criteria are not sufficiently sensitive for the diagnosis of type 1 IgG4-related autoimmune pancreatitis (IgG4-related AIP), they are adequately sensitive for IgG4-related Mikulicz's disease (MD) and kidney disease (KD). In addition, the comprehensive diagnostic criteria, combined with organ-specific diagnostic criteria, have increased the sensitivity of diagnosis to 100% for IgG4-related MD, KD, and AIP. Our comprehensive diagnostic criteria for IgG4-RD are practically useful for general physicians and nonspecialists.
  Modern Rheumatology 01/2012; 22(1):21-30. · 1.58 Impact Factor
• Source

  Available from: Shigeki Momohara

  Article: ACPA-negative RA consists of two genetically distinct subsets based on RF positivity in Japanese.

  Chikashi Terao, Koichiro Ohmura, Katsunori Ikari, Yuta Kochi, Etsuko Maruya, Masaki Katayama, Kimiko Yurugi, Kota Shimada, Akira Murasawa, Shigeru Honjo, [......], Keitaro Matsuo, Kazuo Tajima, Akari Suzuki, Kazuhiko Yamamoto, Shigeki Momohara, Hisashi Yamanaka, Ryo Yamada, Hiroo Saji, Fumihiko Matsuda, Tsuneyo Mimori
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  ABSTRACT: HLA-DRB1, especially the shared epitope (SE), is strongly associated with rheumatoid arthritis (RA). However, recent studies have shown that SE is at most weakly associated with RA without anti-citrullinated peptide/protein antibody (ACPA). We have recently reported that ACPA-negative RA is associated with specific HLA-DRB1 alleles and diplotypes. Here, we attempted to detect genetically different subsets of ACPA-negative RA by classifying ACPA-negative RA patients into two groups based on their positivity for rheumatoid factor (RF). HLA-DRB1 genotyping data for totally 954 ACPA-negative RA patients and 2,008 healthy individuals in two independent sets were used. HLA-DRB1 allele and diplotype frequencies were compared among the ACPA-negative RF-positive RA patients, ACPA-negative RF-negative RA patients, and controls in each set. Combined results were also analyzed. A similar analysis was performed in 685 ACPA-positive RA patients classified according to their RF positivity. As a result, HLA-DRB1*04:05 and *09:01 showed strong associations with ACPA-negative RF-positive RA in the combined analysis (p = 8.8×10(-6) and 0.0011, OR: 1.57 (1.28-1.91) and 1.37 (1.13-1.65), respectively). We also found that HLA-DR14 and the HLA-DR8 homozygote were associated with ACPA-negative RF-negative RA (p = 0.00022 and 0.00013, OR: 1.52 (1.21-1.89) and 3.08 (1.68-5.64), respectively). These association tendencies were found in each set. On the contrary, we could not detect any significant differences between ACPA-positive RA subsets. As a conclusion, ACPA-negative RA includes two genetically distinct subsets according to RF positivity in Japan, which display different associations with HLA-DRB1. ACPA-negative RF-positive RA is strongly associated with HLA-DRB1*04:05 and *09:01. ACPA-negative RF-negative RA is associated with DR14 and the HLA-DR8 homozygote.
  PLoS ONE 01/2012; 7(7):e40067. · 4.09 Impact Factor