Background The anti-Ku antibodies are directed against a DNA-binding nuclear protein complex composed of 2 polypeptides of 86 and 70 kDa in a 1:1 ratio. These autoantibodies were originally described in 1981 by Mimori et al. in patients with systemic sclerosis (SSc)-polymyositis (PM) overlap syndromes, but further studies have associated anti-Ku antibodies with a wide variety of autoimmune diseases (AD) including systemic lupus erythematosus, Sjögren's syndrome, SSc, mixed connective tissue disease (MCTD) and idiopathic lung fibrosis (ILF).

Objectives To describe the clinical and immunological features of patients with positive anti-Ku antibodies treated in a Spanish tertiary center.

Methods We performed a retrospective study of anti-Ku-positive patients seen in our center during the period 2007–2015. Positivity for anti-Ku was detected through line immunoassay and confirmed by indirect immunofluorescence. Demographic, clinical, therapeutic and outcome data were obtained through review of their medical records.

Results During the study period 14 anti-Ku-positive patients were found, 10 of them women (71.4%), mostly Caucasian (85.7%) with a mean age of 53.2 years (range: 14–79). Three patients had ES-PM overlap syndrome, 3 dermatomyositis (1 paraneoplastic), 2 unspecified myositis, 1 diffuse cutaneous SSc, 1 limited cutaneous SSc, 1 SSc sine scleroderma, 1 MCTD, 1 ILF and 1 IgM mesangial glomerulonephritis. The most frequent clinical manifestations were: arthralgia 50%, Raynaud 42.8%, muscular weakness 42.8%, hand edema 42.8%, sclerodactyly 35.7%, dyspnea 35.7%, myalgia 28.5% and Gottron papules 28.5%. Interstitial lung disease (ILD) was detected in 6 cases (42.8%), 3 with radiological pattern of usual interstitial pneumonia, 2 nonspecific interstitial pneumonia and 1 without a characteristic pattern. The acute phase reactants were elevated in 5 cases and muscle enzymes in 9 (creatine kinase mean value 1096 IU/L, range: 309–2256), 3 showed lymphopenia and 4 polyclonal hypergammaglobulinemia. Myositis (demonstrated by electromyography and muscle biopsy) was present in 4 cases (29.5%). Antinuclear antibodies were positive in 12 cases (85.7%), anti-Ro/SSA antibodies in 3 (21.4%) and anti-centromere, anti-RNP, anti-DNA, anti-PM/Scl75 and anti-MDA5 in 1 case each (7.1%). After a mean follow-up of 35.2 months 4 patients with ILD developed impairment of respiratory function tests despite treatment with corticosteroids and immunosuppressants, but not worsening of myositis or mortality.

Conclusions The features of anti-Ku-positive patients in our series are comparable to those reported in other series published. These antibodies are not specific markers of any AD but are more common in overlap syndromes, so that should be considered in these disorders, especially when myositis is present. ILD frequency was relatively high and the outcome was unfavorable in most cases. Anti-Ku antibodies have been associated with severe and corticoresistant ILD but not with a significant risk of malignancy.

1. Franceschini F et al. Anti-Ku antibodies in connective tissue diseases: clinical and serological evaluation of 14 patients. J Rheumatol. 2002

2. Rigolet A et al. Inflammatory myopathies with anti-Ku antibodies: a prognosis dependent on associated lung disease. Medicine (Baltimore). 2012

Disclosure of Interest None declared