Autoantibodies to the Ku antigen, which are strongly associated with systemic autoimmunity in Japanese patients in contrast to SLE (~15-50%) and overlap syndromes in Americans,¹ are also found in some patients with mixed connective tissue disease, scleroderma, polymyositis (~5-15%), Graves disease and primary pulmonary hypertension (~23%) and, hence, are not diagnostic for any particular autoimmune disease.^1-6 Unlike the Ki autoantigen, which is a 32 kd nuclear protein of unknown function, the Ku autoantigen is a heterodimeric nucleolar protein consisting of 70 and 80-86 kd subunits which together with a 350 kd catalytic subunit is the DNA-binding component of a DNA-dependent protein kinase involved in double-stranded DNA repair and V(D)J recombination.¹ Ku autoantibodies can be detected by DD, radioimmunoprecipitation, antigen-capture EIA and immunoblot; EIA using purified native human Ku antigen is more sensitive than DD, and is 79% sensitive and 94% specific versus immunoprecipitation.¹ The pathogenic role and clinical relevance of Ku autoantibodies are unknown.

Ku antigen is induced in response to the cytokines IL-13 and IL-4, and a 29 bp region within the -353 to -304 bp region of the 15-Lipoxygenase-1 (15-LO-1) promoter is required for its binding and subsequent induction of 15-LO-1 gene expression.⁷ These findings may provide an important link between the established dysregulated function of Ku antigen in auto-immune diseases, such as systemic lupus erythematosus and thyroiditis, and the increasingly recognized 'anti-inflammatory' role of 15-LO-1. A recent study ascertained the clinical and serological associations of anti-Ku antibody to conclude that anti-Ku antibody is found in a wide variety of connective tissue syndromes.⁸ While several patients fulfilled diagnostic criteria for SLE, scleroderma and RA, their clinical features were usually mild and did not form a distinctive clinical pattern. Common features associated with anti-Ku were Raynaud's phenomenon, arthralgia, skin thickening, and esophageal reflux; few patients had associated autoantibody specificities found in SLE or scleroderma. ⁸