{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:22:55Z","timestamp":1787239375684,"version":"build-2736575974"},"reference-count":29,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,7,31]],"date-time":"2017-07-31T00:00:00Z","timestamp":1501459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Anti-centromere antibody (ACA) is one of the classical anti-nuclear antibody (ANA) staining patterns. However, characteristics of ACA in comparison with the other ANA patterns and clinical features of ACA-positive subjects have not been elucidated. Here, we examined all ANA patterns by indirect immunofluorescence for 859 rheumatoid arthritis (RA) patients. Together with the ANA data of 9,575 healthy volunteers, we compared distributions of the ANA levels. ACA was the only ANA that demonstrated a definite bimodal distribution of levels. ACA showed significantly higher levels than the other ANA staining patterns in both RA and healthy population (p\u2009&lt;\u20090.0001). ACA-positivity was associated with old age and was observed more in females. We further recruited another cohort of 3,353 RA patients and confirmed the findings. ACA was also associated with Raynaud\u2019s phenomenon (p\u2009=\u20096.8\u2009\u00d7\u200910\n                    <jats:sup>\u221211<\/jats:sup>\n                    ) in RA. As a conclusion, ACA displays a specific ANA staining pattern with a bimodal distribution, and ACA-positive RA may constitute a distinct subset with specific clinical features.\n                  <\/jats:p>","DOI":"10.1038\/s41598-017-07137-4","type":"journal-article","created":{"date-parts":[[2017,7,25]],"date-time":"2017-07-25T07:56:05Z","timestamp":1500969365000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Anti-centromere antibody exhibits specific distribution levels among anti-nuclear antibodies and may characterize a distinct subset in rheumatoid arthritis"],"prefix":"10.1038","volume":"7","author":[{"given":"Nobuo","family":"Kuramoto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Ohmura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsunori","family":"Ikari","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichiro","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moritoshi","family":"Furu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriyuki","family":"Yamakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motomu","family":"Hashimoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromu","family":"Ito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takao","family":"Fujii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosaku","family":"Murakami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ran","family":"Nakashima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Imura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoichiro","family":"Yukawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Yoshifuji","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsuo","family":"Taniguchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shigeki","family":"Momohara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Yamanaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumihiko","family":"Matsuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuneyo","family":"Mimori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikashi","family":"Terao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,7,31]]},"reference":[{"key":"7137_CR1","doi-asserted-by":"publisher","first-page":"1627","DOI":"10.1073\/pnas.77.3.1627","volume":"77","author":"Y Moroi","year":"1980","unstructured":"Moroi, Y., Peebles, C., Fritzler, M. J., Steigerwald, J. & Tan, E. M. Autoantibody to centromere (kinetochore) in scleroderma sera. Proc Natl Acad Sci USA \n                           77, 1627\u20131631 (1980).","journal-title":"Proc Natl Acad Sci USA"},{"key":"7137_CR2","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1016\/0002-9343(80)90462-3","volume":"69","author":"MJ Fritzler","year":"1980","unstructured":"Fritzler, M. J. & Kinsella, T. D. The CREST syndrome: a distinct serologic entity with anticentromere antibodies. Am J Med \n                           69, 520\u2013526 (1980).","journal-title":"Am J Med"},{"key":"7137_CR3","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1002\/art.1780260714","volume":"26","author":"D Makinen","year":"1983","unstructured":"Makinen, D., Fritzler, M., Davis, P. & Sherlock, S. Anticentromere antibodies in primary biliary cirrhosis. Arthritis rheum \n                           26, 914\u2013917 (1983).","journal-title":"Arthritis rheum"},{"key":"7137_CR4","first-page":"2238","volume":"28","author":"K Katano","year":"2001","unstructured":"Katano, K., Kawano, M., Koni, I., Sugai, S. & Muro, Y. Clinical and laboratory features of anticentromere antibody positive primary Sjogren\u2019s syndrome. J Rheumatol \n                           28, 2238\u20132244 (2001).","journal-title":"J Rheumatol"},{"key":"7137_CR5","doi-asserted-by":"publisher","first-page":"297","DOI":"10.1093\/rheumatology\/32.4.297","volume":"32","author":"PG Vlachoyiannopoulos","year":"1993","unstructured":"Vlachoyiannopoulos, P. G., Drosos, A. A., Wiik, A. & Moutsopoulos, H. M. Patients with anticentromere antibodies, clinical features, diagnosies and evolution. Br J Rheumatol \n                           32, 297\u2013301 (1993).","journal-title":"Br J Rheumatol"},{"key":"7137_CR6","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1007\/BF02242937","volume":"13","author":"M Zuber","year":"1994","unstructured":"Zuber, M. & Gotzen, R. & Filler, I. Clinical correlation of anticentromere antibodies. Clin Rheumatol \n                           13, 427\u2013432 (1994).","journal-title":"Clin Rheumatol"},{"key":"7137_CR7","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s10067-005-0005-4","volume":"25","author":"K Pakunpanya","year":"2006","unstructured":"Pakunpanya, K. et al. Incidence and clinical correlation of anticentromere antibody in Thai patients. Clin Rheumatol \n                           25, 325\u2013328, doi:10.1007\/s10067-005-0005-4 (2006).","journal-title":"Clin Rheumatol"},{"key":"7137_CR8","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.1002\/art.38867","volume":"66","author":"C Terao","year":"2014","unstructured":"Terao, C. et al. Association between antinuclear antibodies and the HLA class II locus and heterogeneous characteristics of staining patterns: the Nagahama study. Arthritis Rheumatol \n                           66, 3395\u20133403, doi:10.1002\/art.38867 (2014).","journal-title":"Arthritis Rheumatol"},{"key":"7137_CR9","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1111\/j.1365-2230.1994.tb01199.x","volume":"19","author":"HL Chan","year":"1994","unstructured":"Chan, H. L., Lee, Y. S., Hong, H. S. & Kuo, T. T. Anticentromere antibodies (ACA): clinical distribution and disease specificity. Clin Exp Dermatol \n                           19, 298\u2013302 (1994).","journal-title":"Clin Exp Dermatol"},{"key":"7137_CR10","doi-asserted-by":"publisher","first-page":"178","DOI":"10.1111\/j.1399-0004.1989.tb03185.x","volume":"36","author":"CM Deighton","year":"1989","unstructured":"Deighton, C. M., Walker, D. J., Griffiths, I. D. & Roberts, D. F. The contribution of HLA to rheumatoid arthritis. Clin Genet \n                           36, 178\u2013182 (1989).","journal-title":"Clin Genet"},{"key":"7137_CR11","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1016\/j.ejim.2013.06.013","volume":"24","author":"P Coppo","year":"2013","unstructured":"Coppo, P. et al. Clinical significance of autoantibodies to the pericentromeric heterochromatin protein 1a protein. Eur J Intern Med \n                           24, 868\u2013871 (2013).","journal-title":"Eur J Intern Med"},{"key":"7137_CR12","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/S0002-9343(97)00023-5","volume":"103","author":"G Spencer-Green","year":"1997","unstructured":"Spencer-Green, G., Alter, D. & Wilch, H. G. Test performance in systemic sclerosis: anti-centromere and anti-Scl-70 antibodies. Am J Med \n                           103, 242\u2013248 (1997).","journal-title":"Am J Med"},{"key":"7137_CR13","doi-asserted-by":"publisher","unstructured":"Bournia, V. K., Diamanti, K. D., Vlachoyiannopoulos, P. G. & Moutsopoulos, H. M. Anticentromere antibody positive Sjogren\u2019s Syndrome: a retrospective descriptive analysis. Arthritis Res Ther \n                           12, doi:10.1186\/ar2958 (2010).","DOI":"10.1186\/ar2958"},{"key":"7137_CR14","first-page":"785","volume":"64","author":"P Caramaschi","year":"1997","unstructured":"Caramaschi, P. et al. Sjogren\u2019s syndrome with anticentromere antibodies. Revue Rhum Engl Ed \n                           64, 785\u2013788 (1997).","journal-title":"Revue Rhum Engl Ed"},{"key":"7137_CR15","first-page":"618","volume":"17","author":"FN Skopouli","year":"1990","unstructured":"Skopouli, F. N. et al. Raynaud\u2019s phenomenon in primary Sj\u00f6gren\u2019s syndrome. J Rheumatol \n                           17, 618\u2013620 (1990).","journal-title":"J Rheumatol"},{"key":"7137_CR16","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/art.1780310302","volume":"31","author":"FC Arnett","year":"1988","unstructured":"Arnett, F. C. et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum \n                           31, 315\u2013324 (1988).","journal-title":"Arthritis Rheum"},{"key":"7137_CR17","doi-asserted-by":"publisher","first-page":"2569","DOI":"10.1002\/art.27584","volume":"62","author":"D Aletaha","year":"2010","unstructured":"Aletaha, D. et al. Rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Arthritis Rheum \n                           62, 2569\u20132581, doi:10.1002\/art.27584 (2010).","journal-title":"Arthritis Rheum"},{"key":"7137_CR18","unstructured":"Aletaha, D. et al. rheumatoid arthritis classification criteria: an American College of Rheumatology\/European League Against Rheumatism collaborative initiative. Ann Rheum Dis \n                           69, 1580\u20131588, doi:1136\/ard.2010.138461 (2010)."},{"key":"7137_CR19","doi-asserted-by":"publisher","unstructured":"Terao, C. et al. ACPA-negative RA consists of two fenetically distinct subsets based on RF positivity in Japanese. PloS One \n                           7, doi:10.1371\/journal.pone.0040067 (2012).","DOI":"10.1371\/journal.pone.0040067"},{"key":"7137_CR20","doi-asserted-by":"publisher","unstructured":"Terao, C. et al. Three groups in the 28 joints for rheumatoid arthritis synovitis\u2013analysis using more than 17,000 assessments in the KURAMA database. PloS One \n                           8, doi:10.1371\/journal.pone.0059341 (2013).","DOI":"10.1371\/journal.pone.0059341"},{"key":"7137_CR21","doi-asserted-by":"publisher","unstructured":"Innala, L. et al. Age at onset determines severity and choice of treatment in early rheumatoid arthritis: a prospective study. Arthritis Res Ther \n                           16, doi:10.1186\/ar4540 (2014).","DOI":"10.1186\/ar4540"},{"key":"7137_CR22","doi-asserted-by":"publisher","unstructured":"Mewar, D. et al. Independent associations of anti-cyclic citrullinated peptide antibodies and rheumatoid factor with radiographic severity of rheumatoid arthritis. Arthritis Res Ther \n                           8, doi:10.1186\/ar2017 (2006).","DOI":"10.1186\/ar2017"},{"key":"7137_CR23","first-page":"159","volume":"11","author":"LH Jearn","year":"2004","unstructured":"Jearn, L. H. & Kim, T. Y. Clinical significance of anti-centromere antibody in rheumatoid arthritis. J Korean Reum Assoc \n                           11, 159\u2013164 (2004).","journal-title":"J Korean Reum Assoc"},{"issue":"Suppl","key":"7137_CR24","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1007\/BF02205562","volume":"9","author":"CGM Kallenberg","year":"1990","unstructured":"Kallenberg, C. G. M. Anti-centromere antibodies (ACA). Clin Rheumatol \n                           9(Suppl), 136\u2013140 (1990).","journal-title":"Clin Rheumatol"},{"key":"7137_CR25","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1002\/art.1780270202","volume":"27","author":"VD Steen","year":"1984","unstructured":"Steen, V. D., Ziegler, G. L., Rodnon, G. P. & Medsger, T. A. Clinical and laboratory associations of anticentromere antibody in patients with progressive systemic sclerosis. Arthritis Rheum \n                           27, 125\u2013131 (1984).","journal-title":"Arthritis Rheum"},{"key":"7137_CR26","first-page":"743","volume":"26","author":"D van der Heijde","year":"1999","unstructured":"van der Heijde, D. How to read radiographs according to the Sharp\/van der Heijde method. J Rheumatol \n                           26, 743\u2013745 (1999).","journal-title":"J Rheumatol"},{"key":"7137_CR27","doi-asserted-by":"publisher","first-page":"3113","DOI":"10.1002\/art.39306","volume":"67","author":"C Terao","year":"2015","unstructured":"Terao, C. et al. Rheumatoid Factor Is Associated With the Distribution of Hand Joint Destruction in Rheumatoid Arthritis. Arthritis Rheumatol \n                           67, 3113\u20133123, doi:10.1002\/art.39306 (2015).","journal-title":"Arthritis Rheumatol"},{"issue":"2298\u20132304","key":"7137_CR28","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1093\/rheumatology\/keq.","volume":"49","author":"K Ohmura","year":"2010","unstructured":"Ohmura, K. et al. Anti-citrullinated peptide antibody-negative RA is a genetically distinct subset: a definitive study using only bone-erosive ACPA-negative rheumatoid arthritis. Rheumatology \n                           49(2298\u20132304), 273, doi:10.1093\/rheumatology\/keq. (2010).","journal-title":"Rheumatology"},{"key":"7137_CR29","doi-asserted-by":"publisher","first-page":"1150","DOI":"10.1136\/annrheumdis-2016-210645","volume":"76","author":"C Terao","year":"2017","unstructured":"Terao, C. et al. Transethnic meta-analysis identifies GSDMA and PRDM1 as susciptibility genes to systemic sclerosis. Ann Rheum Dis \n                           76, 1150\u20131158, doi:10.1136\/annrheumadis-2016-210645 (2017).","journal-title":"Ann Rheum Dis"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07137-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07137-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07137-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,23]],"date-time":"2022-12-23T02:39:27Z","timestamp":1671763167000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-017-07137-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,7,31]]},"references-count":29,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2017,12]]}},"alternative-id":["7137"],"URL":"https:\/\/doi.org\/10.1038\/s41598-017-07137-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,7,31]]},"assertion":[{"value":"20 December 2016","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 June 2017","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"31 July 2017","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare that they have no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6911"}}