Franceschini, et al: Anti-Ku antibodies 1393 From the Clinical Immunology Unit, Spedali Civili, University of Brescia, Brescia; the Division of Internal Medicine, Ospedale di Montichiari, Brescia; and the Division of Rheumatology, University of Padova, Padova, Italy. F. Franceschini, MD; I. Cavazzana, MD; D. Generali, MD; M. Quinzanini, BSc, Clinical Immunology Unit, University of Brescia; L. Viardi, MD, Division of Internal Medicine, Ospedale di Montichiari; A. Ghirardello, PhD; A. Doria, MD, Division of Rheumatology, University of Padova; R. Cattaneo, MD, Clinical Immunology Unit, University of Brescia. Address reprint requests to Dr. F. Franceschini, Servizio di Immunologia Clinica — Spedali Civili, P. le Spedali Civili, 1, 25100 Brescia, Italy. E-mail: cattaneo@master.cci.unibs.it Submitted July 3, 2001; revision accepted January 9, 2002. The Ku antigen is a DNA-binding nuclear protein complex composed of 2 polypeptides of 86 and 70 kDa in 1:1 ratio 1–4 . Autoantibodies to Ku were originally described in sera from patients with a polymyositis-scleroderma (PM/SSc) overlap syndrome 1 . Although originally thought to be relatively specific for this rare autoimmune disease, autoantibodies to Ku are also found in sera of some patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), mixed connective tissue disease (MCTD), and other clinical condi- tions 2,5-8 . Anti-Ku reactivity was investigated with different methodological approaches in different studies. While Mimori, et al 1 originally used immunodiffusion assay to detect anti-Ku antibodies, other investigators have used ELISA, immunoblot (IB), or immunoprecipitation assays 9–11 . Moreover, differences in prevalence of the anti- Ku antibodies have been reported in African-American SLE patients compared to Caucasians 12 . Therefore, case selection and clinical and racial differences in the cohort of patients studied and methods employed to detect anti-Ku antibodies may account for some of the disagreements reported in the literature. Currently, the prevalence of antibodies to Ku protein in various autoimmune diseases varies widely, ranging from 3% with IB analysis to 55% using a capture ELISA 1,2,5,11,13 . We described 14 patients with anti-Ku antibodies and their clinical and serological features. Antibodies were screened with counterimmunoelectrophoresis (CIE) and then tested with IB to correlate the fine specificity of the antibody with the clinical picture and immunological features. MATERIALS AND METHODS Patients. Fourteen patients with anti-Ku antibodies detected by CIE were evaluated. All were attending the Clinical Immunology Unit of Brescia. Anti-Ku Antibodies in Connective Tissue Diseases: Clinical and Serological Evaluation of 14 Patients FRANCO FRANCESCHINI, ILARIA CAVAZZANA, DANIELE GENERALI, MARZIA QUINZANINI, LUIGI VIARDI, ANNA GHIRARDELLO, ANDREA DORIA, and ROBERTO CATTANEO ABSTRACT. Objective. To assess the clinical and serological associations of anti-Ku antibodies. Methods. Fourteen patients with anti-Ku antibody detected by counterimmunoelectrophoresis (CIE) and immunoblot (IB) were retrospectively evaluated. Results. Patients (13 women, one man) had a mean age of 60.3 years (range 19–83). Seven patients had overlap syndromes: 5 polymyositis/scleroderma (PM/SSc), one systemic lupus erythematosus (SLE)/SSc/PM, and one SLE/PM. Three additional patients had undifferentiated connective tissue disease, 2 primary Sjögren’s syndrome (SS), one psoriatic arthritis, and one SSc. The clinical mani- festations most frequently recorded were arthralgias (86%), myositis (50%) and Raynaud’s phenom- enon (78.6%). Five patients had esophageal dysmotility, while 6 showed interstitial pulmonary fibrosis (4 of them with reduced DLCO). No case of pulmonary hypertension was observed. All patients had very high titer of ANA with speckled and nucleolar pattern. All the sera were positive for anti-Ku antibodies by CIE: all but one were confirmed by IB. Eight sera contained isolated anti- bodies to Ku proteins: both subunits were recognized in 7 cases, while isolate reactivity to the 70 kDa protein was detected in one case. Five sera contained additional antibody specificities: anti-Ro 60 kDa in 4 cases, and anti-La/SSB, anti-SL, and anti-PM-Scl in one case each. Conclusion. Anti-Ku antibody is found in a wide spectrum of connective tissue diseases including overlap syndromes with SSc and myositis. Raynaud’s phenomenon and muscular and joint involve- ment are the most frequent clinical features associated with anti-Ku antibodies, which are frequently detected in association with anti-Ro/SSA and/or other antinuclear specificities. (J Rheumatol 2002;29:1393–7) Key Indexing Terms: ANTI-KU ANTIBODIES OVERLAP SYNDROMES ANTI-ENA ANTIBODIES COUNTERIMMUNOELECTROPHORESIS IMMUNOBLOTTING Personal non-commercial use only. The Journal of Rheumatology Copyright © 2002. All rights reserved. www.jrheum.org Downloaded on September 2, 2021 from