M Mahler1, A Swart2, J Wu3, M Szmyrka-Kaczmarek4, J-L Senécal5, Y Troyanov6, J G Hanly7, M J Fritzler8. 1. Inova Diagnostics Inc., San Diego, USA mmahler@inovadx.com m.mahler.job@web.de. 2. Neuss Clinic for Rheumatology Dr Gürtler, Neuss, Germany. 3. Inova Diagnostics Inc., San Diego, USA. 4. Wroclaw Medical University, Poland. 5. Department of Medicine, Division of Rheumatology, and Laboratory for Research in Autoimmunity, Research Centre of the Centre Hospitalier de l'Université de Montréal, University of Montreal Faculty of Medicine, Montreal, Canada. 6. Hôpital du Sacré-Coeur, University of Montreal, Montreal, Canada. 7. Faculty of Medicine, Dalhousie University and Nova Scotia Health Authority Halifax, Canada. 8. Cumming School of Medicine, University of Calgary, Calgary, Canada.
Abstract
BACKGROUND: Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay. PATIENTS AND METHODS: Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositis patients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLE patient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review. RESULTS AND FINDINGS: In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious disease patients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. CONTROLS: In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA. CONCLUSION: Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc.
BACKGROUND: Autoantibodies targeting Ku, an abundant nuclear protein with DNA helicase activity, have been reported in patients with systemic autoimmune rheumatic diseases. Little is known about the clinical associations of anti-Ku antibodies, especially when novel diagnostic technologies are used. The objective of the present study was to analyse the prevalence of anti-Ku antibodies in different medical conditions using a novel chemiluminescent immunoassay. PATIENTS AND METHODS: Serum samples from adult patients with systemic lupus erythematosus (SLE, n=305), systemic sclerosis (SSc, n=70) and autoimmune myositispatients (AIM, n=109) were the primary focus of the study. Results were compared with disease controls (rheumatoid arthritis, RA, n=30; infectious diseases, n=17) and healthy individuals (n=167). In addition, samples submitted for routine autoantibody testing from patients referred to a rheumatology clinic (n=1078) were studied. All samples were tested for anti-Ku antibodies by QUANTA Flash Ku chemiluminescent immunoassay (research use only, Inova Diagnostics, San Diego, USA) using full length recombinant human Ku. SLEpatient samples were also tested for other autoantibodies. Clinical data of anti-Ku antibody positive patients (high titres) were obtained by retrospective chart review. RESULTS AND FINDINGS: In the disease cohorts, 30/305 (9.8%) SLE, 3/70 (4.3%) systemic sclerosis and 4/109 (3.7%) autoimmune myositis (AIM) patients were positive, respectively. The four positive AIM patients had an overlap myositis syndrome that included two patients with SLE. The three systemic sclerosis (SSc) positive samples had diagnoses of SSc/SLE overlap, diffuse cutaneous SSc, and early edematous phase SSc. In the control cohorts, 2/170 (1.2%) healthy individuals (all low titre), 0/30 (0.0%) (RA) and 0/17 (0.0%) infectious diseasepatients were positive. The area under the curve values were: 0.75 for SLE vs. controls, 0.68 for SSc vs. controls and 0.37 for AIM vs. CONTROLS: In the rheumatology clinic referral cohort, 12/1078 (1.1%) were positive for anti-Ku antibodies, nine showing low and three high titres. The diagnoses of the three high positive anti-Ku positive patients were: probable SLE, mixed connective tissue disease (MCTD) and ANA positive RA. CONCLUSION: Anti-Ku antibodies detected by chemiluminescent immunoassay are most prevalent in SLE. When found in AIM and SSc, they were associated with overlap syndrome and early SSc.
Authors: Maria Casal-Dominguez; Iago Pinal-Fernandez; Assia Derfoul; Rose Graf; Harlan Michelle; Jemima Albayda; Eleni Tiniakou; Brittany Adler; Sonye K Danoff; Thomas E Lloyd; Lisa Christoper-Stine; Julie J Paik; Andrew L Mammen Journal: Semin Arthritis Rheum Date: 2021-04-28 Impact factor: 5.431