ABS0181 CLINICAL SIGNIFICANCE OF ANTI-Ku ANTIBODIES IN A TUNISIAN COHORT

Abstract

<h2>Abstract</h2><h3>Background:</h3> Among all myositis-associated antibodies, autoantibodies against the Ku complex (anti-Ku) are considered among the rarest, with unclear clinical significance. Some studies suggest that anti-Ku antibodies may serve as a hallmark of myositis overlap syndrome, while others have found associations with lupus nephritis and muscle damage. Ethnicity may contribute to the variability observed between different cohorts. However, most of the available data come from North American and European populations, while data from Africa remain scarce. <h3>Objectives:</h3> The aim of our study was to evaluate the clinical significance of anti-Ku antibodies in the Tunisian population. <h3>Methods:</h3> A multicenter, retrospective, observational, and longitudinal study was conducted using data from the Pasteur Institute of Tunis database, which includes all immunological assay results for patients referred to the Clinical Immunology Department. For this study, we identified and extracted patients who tested positive for anti-Ku antibodies between January 2014 and December 2024. Anti-Ku antibody detection was performed using the EUROLINE Line Dot Immunoassay (LDIA) (Euroimmun®). Band intensity was measured using the EUROLineScan (SU) system. Clinical data for these patients, regardless of their diagnosis, were then collected from their referring centers. <h3>Results:</h3> Forty-two patients were included in the study, with a male-to-female ratio of 0.3. The mean age at disease onset was 52.6 ± 17.2 years. Fifteen patients showing isolated anti-Ku positivity (35.7%) and 27 showed multiple positivity (64,3%). Most frequent associated abs were: Anti-Ro-52 (n=13; 48,1%); anti-Sm (n=7; 25,9%); anti-RNP (n=7; 25,9%); anti-SSA (n=7; 25,9%); Pm/Scl 75 (n=5; 18,5%); Pm/Scl100 (n=4; 14,8%); Pl-12 (n=3; 11,1%). The most common diagnoses were overlap syndrome (n=16; 38,09%), SLE (n=6; 14.3%), and systemic sclerosis (n=3; 7.1%), undifferenciated connective tissue disease (n=3; 7,1%); mediastino-pulmonary sarcoidosis (n=2; 4.8%), dermatomyositis (n=1; 2.4%), antisynthetase syndrome (n=1; 2.4%), SSc-SLE overlap syndrome (n=1; 2.4%), primary Sjögren's disease (n=1; 2.4%), autoimmune hepatitis (n=1; 2.4%), microscopic polyangiitis (n=1; 2.4%), Crohn's disease with central nervous system vasculitis (n=1; 2.4%), bacterial pneumonia (n=1; 2.4%), left heart failure decompensation (n=1; 2.4%), pulmonary embolism (n=1; 2.4%), diabetic ketosis (n=1; 2.4%), and Morbihan disease (n=1; 2.4%). Muscle weakness was observed in 31% of patients, and interstitial lung disease (ILD) occurred in 40.5%. Three patients had cancers in remission at the time of the study. A significant correlation was found between anti-Ku antibody levels and the severity of muscle weakness (p=0.027), with anti-Ku Abs intensity above 40 SU associated with the highest risk for muscle weakness (p=0.0063). Anti-Ku positivity was significantly linked to elevated levels of CK (p=0,034), AST (p=0.08), and ALT (p=0.04). ILD was significantly associated with anti-Ku antibodies (p=0.014), with anti-Ku Abs levels above 40 SU showing the highest risk for ILD onset (p=0.022) in multivariate analysis. Anti-Ku titers were also correlated with left ventricular ejection fraction (p=0.038). No correlation was found with forced vital capacity, renal, skin or osteoarticular involvement. <h3>Conclusion:</h3> To our knowledge, this is the first large-scale study in Africa to investigate the clinical significance of anti-Ku antibodies. Our findings suggest an association of anti-Ku Abs with ILD and myositis, with potential prognostic implications. Larger comparative studies are needed to validate these results and further investigate disease progression and treatment response. <h3>REFERENCES:</h3> <b>NIL</b>. <h3>Acknowledgements:</h3> <b>NIL</b>. <h3>Disclosure of Interests:</h3> <b>None declared</b>. © The Authors 2025. This abstract is an open access article published in Annals of Rheumatic Diseases under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Neither EULAR nor the publisher make any representation as to the accuracy of the content. The authors are solely responsible for the content in their abstract including accuracy of the facts, statements, results, conclusion, citing resources etc.