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

Arthritis Res Ther. 2012 Jan 6;14(1):R2. doi: 10.1186/ar3550.

Abstract

Introduction: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antigens, Nuclear / immunology*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology*
  • Bone Diseases / blood
  • Bone Diseases / immunology*
  • Cohort Studies
  • Counterimmunoelectrophoresis
  • DNA-Binding Proteins / immunology*
  • Europe
  • Female
  • Humans
  • Immunoassay
  • Immunoblotting
  • Joint Diseases / blood
  • Joint Diseases / immunology*
  • Ku Autoantigen
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Middle Aged
  • Polymyositis / blood
  • Polymyositis / immunology
  • Principal Component Analysis*
  • Scleroderma, Systemic / blood
  • Scleroderma, Systemic / immunology
  • Sjogren's Syndrome / blood
  • Sjogren's Syndrome / immunology
  • Young Adult

Substances

  • Antigens, Nuclear
  • Autoantibodies
  • DNA-Binding Proteins
  • Xrcc6 protein, human
  • Ku Autoantigen