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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

Katja Lakota1, Gerhard G Thallinger2, Snezna Sodin-Semrl1*, Blaz Rozman1, Ales Ambrozic1, Matija Tomsic1, Sonja Praprotnik1, Sasa Cucnik1, Katjusa Mrak-Poljsak1, Angela Ceribelli3, Ilaria Cavazzana3, Franco Franceschini3, Jiri Vencovsky4, Laszlo Czirják5, Cecilia Varjú5, Gunther Steiner6, Martin Aringer6, Bojana Stamenkovic7, Oliver Distler8, Marco Matucci-Cerinic8 and Tanja Kveder1

  • * Corresponding author: Snezna Sodin-Semrl

  • † Equal contributors

Author Affiliations

1 Department of Rheumatology, University Medical Centre, Ljubljana, Slovenia

2 Institute for Genomics and Bioinformatics, Graz University of Technology, Graz, Austria

3 Rheumatology & Clinical Immunology Unit, Spedali Civili, Brescia, Italy

4 Institute of Rheumatology, Prague, Czech Republic

5 Department of Immunology and Rheumatology, Medical School, University of Pécs, Pécs, Hungary

6 Department of Rheumatology, Internal Medicine III, Medical University of Vienna, Vienna, Austria

7 Department for Rheumatology, Institute for Treatment and Rehabilitation of Rheumatic and Cardiovascular diseases, Niska Banja, Serbia

8 Department of BioMedicine, Division of Rheumatology AOUC, Denothe Center, University of Florence, Florence, Italy

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Arthritis Research & Therapy 2012, 14:R2  doi:10.1186/ar3550

Published: 6 January 2012



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.


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 P 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 prcomp function with standard parameters.


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 Sjögren syndrome.


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 (P = 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.