Objectives: To determine the prevalence of anti-Ku antibodies in 625 patients with systemic sclerosis (SSc) from six European rheumatologic centres and to evaluate their clinical and serologic characteristics.
Methods: Sera of 625 consecutive patients with either limited cutaneous or diffuse cutaneous SSc were tested for antibodies to Ku antigen together with other extractable nuclear antigens by counter-immunoelectrophoresis. A case-control design with calculation of Bootstrap 95% confidence intervals derived from anti-Ku negative control patients was used to evaluate clinical associations of anti-Ku antibodies. Sera of anti-Ku positive SSc patients and control group were additionally tested by immunofluorescence on Hep-2 cell substrates and line immunoassay.
Results: Anti-Ku antibodies were found in sera of 14/625 (2.2%) SSc patients. Ten out of fourteen anti-Ku positive SSc patients had no other anti-ENA antibodies detected by counterimmuno-electrophoresis. Using the case control design, anti-Ku antibodies were significantly associated with musculoskeletal manifestations such as clinical markers of myositis, arthritis, and joint contractures. In addition, a significant negative correlation of anti-Ku antibodies was found with vascular manifestation such as fingertip ulcers and teleangiectasias. There was a striking absence of anti-centromere antibodies as well as anti-PM/Scl antibodies in anti-Ku positive patients. As expected, anti-Scl-70 and punctate nucleolar immunofluorescence pattern were present only in single cases.
Conclusion: This is the largest cohort to date focusing on the prevalence of anti-Ku antibodies in SSc patients. The case control approach was able to demonstrate a clinically distinct subset of anti-Ku positive SSc patients with only relative clinical differences in skeletal features. However, the notable exceptions were signs of myositis. This shows the importance of anti-Ku antibody detection for the prediction of this specific clinical subset.
- anti-Ku antibodies
- case control approach
- multicentre study
- systemic sclerosis