{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T10:54:40Z","timestamp":1778756080038,"version":"3.51.4"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T00:00:00Z","timestamp":1325808000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p>An international cohort study of 73 anti-Ku-positive patients with different connective tissue diseases was conducted to differentiate the anti-Ku-positive populations of patients based on their autoantibody profile and clinical signs\/symptoms and to establish possible correlations between antibodies against Ku p70 and Ku p80 with autoimmune diseases.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Sera of anti-Ku-positive patients were collected from six European centers and were all secondarily tested (in the reference center); 73 were confirmed as positive. Anti-Ku antibodies were detected with counter-immunoelectrophoresis (CIE), line immunoassay (LIA), and immunoblot analyses. All clinical and laboratory data were follow-up cumulative data, except for anti-Ku antibodies. Statistical analyses were performed by using R (V 2.12.1). The Fisher Exact test was used to evaluate the association between anti-Ku antibodies and diagnosis, gender, clinical signs, and other observed antibodies. The <jats:italic>P<\/jats:italic> values were adjusted for multiple testing. Separation of disease populations based on the presence of antibodies and clinical signs was investigated by principal-components analysis, which was performed by using thr\/\/ R's <jats:italic>prcomp<\/jats:italic> function with standard parameters.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>A 16% higher prevalence of anti-Ku p70 was found over anti-Ku p80 antibodies. In 41 (57%) patients, a combination of both was detected. Five (7%) patients, who were CIE and\/or LIA anti-Ku positive, were negative for both subsets, as detected with the immunoblot; 31% of the patients had undifferentiated connective tissue disease (UCTD); 29% had systemic sclerosis (SSc); 18% had systemic lupus erythematosus (SLE); 11% had rheumatoid arthritis; 7% had polymyositis; and 3% had Sj\u00f6gren syndrome.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>A significant positive association was found between female patients with anti-Ku p70 and joint\/bone features, and a significant negative association was found between female patients with anti-Ku p80 only and joint\/bone features (<jats:italic>P<\/jats:italic> = 0.05, respectively). By using the first and the third components of the principal-component analysis (PCA) with 29 parameters evaluated, we observed that the anti-Ku-positive population of UCTD patients had overlapping parameters, especially with SLE, as opposed to SSc, which could be helpful in delineating UCTD patients.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/ar3550","type":"journal-article","created":{"date-parts":[[2012,1,6]],"date-time":"2012-01-06T19:23:30Z","timestamp":1325877810000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["International cohort study of 73 anti-Ku-positive patients: association of p70\/p80 anti-Ku antibodies with joint\/bone features and differentiation of disease populations by using principal-components analysis"],"prefix":"10.1186","volume":"14","author":[{"given":"Katja","family":"Lakota","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gerhard G","family":"Thallinger","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Snezna","family":"Sodin-Semrl","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Blaz","family":"Rozman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ales","family":"Ambrozic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matija","family":"Tomsic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonja","family":"Praprotnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sasa","family":"Cucnik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katjusa","family":"Mrak-Poljsak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angela","family":"Ceribelli","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Cavazzana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Franco","family":"Franceschini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiri","family":"Vencovsky","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laszlo","family":"Czirj\u00e1k","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Varj\u00fa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunther","family":"Steiner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Aringer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bojana","family":"Stamenkovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Distler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Matucci-Cerinic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tanja","family":"Kveder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2012,1,6]]},"reference":[{"key":"3503_CR1","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0921-8777(99)00006-3","volume":"434","author":"C Featherstone","year":"1999","unstructured":"Featherstone C, Jackson SP: Ku, a DNA repair protein with multiple cellular functions?. Mutat Res. 1999, 434: 3-15.","journal-title":"Mutat Res"},{"key":"3503_CR2","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1016\/j.dnarep.2005.04.021","volume":"4","author":"TS Fisher","year":"2005","unstructured":"Fisher TS, Zakian VA: Ku: a multifunctional protein involved in telomere maintenance. DNA Repair (Amst). 2005, 4: 1215-1226. 10.1016\/j.dnarep.2005.04.021.","journal-title":"DNA Repair (Amst)"},{"key":"3503_CR3","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/10409230091169177","volume":"35","author":"R Tuteja","year":"2000","unstructured":"Tuteja R, Tuteja N: Ku autoantigen: a multifunctional DNA-binding protein. Crit Rev Biochem Mol Biol. 2000, 35: 1-33. 10.1080\/10409230091169177.","journal-title":"Crit Rev Biochem Mol Biol"},{"key":"3503_CR4","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/S0889-857X(21)00734-1","volume":"18","author":"WH Reeves","year":"1992","unstructured":"Reeves WH: Antibodies to the p70\/p80 (Ku) antigens in systemic lupus erythematosus. Rheum Dis Clin North Am. 1992, 18: 391-414.","journal-title":"Rheum Dis Clin North Am"},{"key":"3503_CR5","doi-asserted-by":"publisher","first-page":"13588","DOI":"10.1073\/pnas.94.25.13588","volume":"94","author":"A Nussenzweig","year":"1997","unstructured":"Nussenzweig A, Sokol K, Burgman P, Li L, Li GC: Hypersensitivity of Ku80-deficient cell lines and mice to DNA damage: the effects of ionizing radiation on growth, survival, and development. Proc Natl Acad Sci USA. 1997, 94: 13588-13593. 10.1073\/pnas.94.25.13588.","journal-title":"Proc Natl Acad Sci USA"},{"key":"3503_CR6","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1084\/jem.186.6.921","volume":"186","author":"H Ouyang","year":"1997","unstructured":"Ouyang H, Nussenzweig A, Kurimasa A, Soares VC, Li X, Cordon-Cardo C, Li W, Cheong N, Nussenzweig M, Iliakis G, Chen DJ, Li GC: Ku70 is required for DNA repair but not for T cell antigen receptor gene recombination in vivo. J Exp Med. 1997, 186: 921-929. 10.1084\/jem.186.6.921.","journal-title":"J Exp Med"},{"key":"3503_CR7","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1177\/0961203308089442","volume":"17","author":"I Cavazzana","year":"2008","unstructured":"Cavazzana I, Ceribelli A, Quinzanini M, Scarsi M, Airo P, Cattaneo R, Franceschini F: Prevalence and clinical associations of anti-Ku antibodies in systemic autoimmune diseases. Lupus. 2008, 17: 727-732. 10.1177\/0961203308089442.","journal-title":"Lupus"},{"key":"3503_CR8","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.1136\/ard.2007.073981","volume":"67","author":"B Rozman","year":"2008","unstructured":"Rozman B, Cucnik S, Sodin-Semrl S, Czirj\u00e1k L, Varj\u00fa C, Distler O, Huscher D, Aringer M, Steiner G, Matucci-Cerinic M, Guiducci S, Stamenkovic B, Stankovic A, Kveder T: Prevalence and clinical associations of anti-Ku antibodies in patients with systemic sclerosis: a European EUSTAR-initiated multi-centre case-control study. Ann Rheum Dis. 2008, 67: 1282-1286.","journal-title":"Ann Rheum Dis"},{"key":"3503_CR9","doi-asserted-by":"publisher","first-page":"562","DOI":"10.1172\/JCI114199","volume":"84","author":"WH Reeves","year":"1989","unstructured":"Reeves WH, Sthoeger ZM, Lahita RG: Role of antigen selectivity in autoimmune responses to the Ku (p70\/p80) antigen. J Clin Invest. 1989, 84: 562-567. 10.1172\/JCI114199.","journal-title":"J Clin Invest"},{"key":"3503_CR10","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.4049\/jimmunol.145.12.4222","volume":"145","author":"AJ Porges","year":"1990","unstructured":"Porges AJ, Ng T, Reeves WH: Antigenic determinants of the Ku (p70\/p80) autoantigen are poorly conserved between species. J Immunol. 1990, 145: 4222-4228.","journal-title":"J Immunol"},{"key":"3503_CR11","doi-asserted-by":"crossref","first-page":"2678","DOI":"10.4049\/jimmunol.146.8.2678","volume":"146","author":"WH Reeves","year":"1991","unstructured":"Reeves WH, Pierani A, Chou CH, Ng T, Nicastri C, Roeder RG, Sthoeger ZM: Epitopes of the p70 and p80 (Ku) lupus autoantigens. J Immunol. 1991, 146: 2678-2686.","journal-title":"J Immunol"},{"key":"3503_CR12","first-page":"366","volume":"76","author":"M Yaneva","year":"1989","unstructured":"Yaneva M, Arnett FC: Antibodies against Ku protein in sera from patients with autoimmune diseases. Clin Exp Immunol. 1989, 76: 366-372.","journal-title":"Clin Exp Immunol"},{"key":"3503_CR13","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/art.1780310302","volume":"31","author":"FC Arnett","year":"1988","unstructured":"Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger , Michell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002\/art.1780310302.","journal-title":"Arthritis Rheum"},{"key":"3503_CR14","doi-asserted-by":"publisher","first-page":"971","DOI":"10.1016\/S0140-6736(03)14368-1","volume":"362","author":"MC Dalakas","year":"2003","unstructured":"Dalakas MC, Hohlfeld R: Polymyositis and dermatomyositis. Lancet. 2003, 362: 971-982. 10.1016\/S0140-6736(03)14368-1.","journal-title":"Lancet"},{"key":"3503_CR15","doi-asserted-by":"publisher","first-page":"1725","DOI":"10.1002\/art.1780400928","volume":"40","author":"MC Hochberg","year":"1997","unstructured":"Hochberg MC: Updating the American College of Rheumatology revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum. 1997, 40: 1725-","journal-title":"Arthritis Rheum"},{"key":"3503_CR16","first-page":"202","volume":"15","author":"EC LeRoy","year":"1988","unstructured":"LeRoy EC, Black C, Fleischmajer R, Jablonska S, Krieg T, Medsger TA, Rowell N, Wollheim F: Scleroderma (systemic sclerosis): classification, subsets and pathogenesis. J Rheumatol. 1988, 15: 202-205.","journal-title":"J Rheumatol"},{"key":"3503_CR17","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1136\/ard.61.6.554","volume":"61","author":"C Vitali","year":"2002","unstructured":"Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sj\u00f6gren's Syndrome: Classification criteria for Sjogren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis. 2002, 61: 554-558. 10.1136\/ard.61.6.554.","journal-title":"Ann Rheum Dis"},{"key":"3503_CR18","first-page":"244","volume-title":"EULAR Compendium on Rheumatic Diseases","author":"JHW Distler","year":"2009","unstructured":"Distler JHW, Kalden JR, Distler O: Undifferentiated connective tissue disease, overlap syndromes and mixed connective tissue disease. EULAR Compendium on Rheumatic Diseases. Edited by: Bijlsma JWJ. 2009, London: BMJ Publishing Group Ltd, 244-256."},{"key":"3503_CR19","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","volume":"4","author":"S Miyakis","year":"2006","unstructured":"Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R, Derksen RH, DE Groot PG, Koike T, Meroni PL, Reber G, Shoenfeld Y, Tincani A, Vlachoyiannopoulos PG, Krilis SA: International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006, 4: 295-306. 10.1111\/j.1538-7836.2006.01753.x.","journal-title":"J Thromb Haemost"},{"key":"3503_CR20","first-page":"1","volume-title":"Manual of Biological Markers of Disease","author":"C Bunn","year":"1993","unstructured":"Bunn C, Kveder T: Counterimmunoelectrophoresis and immunodiffusion for the detection of antibodies to soluble cellular antigens. Manual of Biological Markers of Disease. Edited by: Van Venrooij WJ, Maini RN. 1993, Nonvell, MA: Kluwer Academic Publishers, 1-12."},{"key":"3503_CR21","volume-title":"R Foundation for Statistical Computing, Vienna, Austria","author":"R Development Core Team","year":"2010","unstructured":"R Development Core Team: R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. 2010, [http:\/\/www.R-project.org\/]"},{"key":"3503_CR22","doi-asserted-by":"publisher","first-page":"60","DOI":"10.3102\/10769986025001060","volume":"25","author":"Y Benjamini","year":"2000","unstructured":"Benjamini Y, Hochberg Y: The adaptive control of the false discovery rate in multiple hypotheses testing. J Behav Educ Statist. 2000, 25: 60-83.","journal-title":"J Behav Educ Statist"},{"key":"3503_CR23","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1002\/1529-0131(199707)40:7<1344::AID-ART20>3.0.CO;2-V","volume":"40","author":"J Wang","year":"1997","unstructured":"Wang J, Dong X, Stojanov L, Kimpel D, Satoh M, Reeves WH: Human autoantibodies stabilize the quaternary structure of Ku antigen. Arthritis Rheum. 1997, 40: 1344-1353.","journal-title":"Arthritis Rheum"},{"key":"3503_CR24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/S1097-2765(00)80108-2","volume":"2","author":"GC Li","year":"1998","unstructured":"Li GC, Ouyang H, Li X, Nagasawa H, Little JB, Chen DJ, Ling CC, Fuks Z, Cordon-Cardo C: Ku70: a candidate tumor suppressor gene for murine T cell lymphoma. Mol Cell. 1998, 2: 1-8. 10.1016\/S1097-2765(00)80108-2.","journal-title":"Mol Cell"},{"key":"3503_CR25","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1016\/S0891-5849(00)00439-1","volume":"29","author":"ED Arrington","year":"2000","unstructured":"Arrington ED, Caldwell MC, Kumaravel TS, Lohani A, Joshi A, Evans MK, Chen HT, Nussenzweig A, Holbrook NJ, Gorospe M: Enhanced sensitivity and long-term G2 arrest in hydrogen peroxide-treated Ku80-null cells are unrelated to DNA repair defects. Free Radic Biol Med. 2000, 29: 1166-1176. 10.1016\/S0891-5849(00)00439-1.","journal-title":"Free Radic Biol Med"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar3550.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar3550\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar3550.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:28:16Z","timestamp":1728383296000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar3550"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,1,6]]},"references-count":25,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,2]]}},"alternative-id":["3503"],"URL":"https:\/\/doi.org\/10.1186\/ar3550","relation":{},"ISSN":["1478-6354"],"issn-type":[{"value":"1478-6354","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,1,6]]},"assertion":[{"value":"6 September 2011","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2012","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"6 January 2012","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R2"}}