POS0221 CLUSTER ANALYSIS IDENTIFIES THREE CLINICAL PATTERNS OF PATIENTS WITH ANTI-KU ANTIBODIES: A MULTICENTRE STUDY OF 154 PATIENTS.
Authors: M. Robert, Y. Nguyen, Y. Allenbach, K. Sacre, B. Terrier, R. Borie, Y. Uzunhan, Z. Amoura, C. Comparon, P. Dieudé, V. Le Guern, C. Morélot-Panzini, M. Humbert, O. Sitbon, C. Goujard, B. Bader-Meunier, B. Fautrel, P. Chrétien, P. Roland-Nicaise, C. Goulvestre, J. L. Charuel, O. Benveniste, L. Mouthon, V. De Lastours, P. Dusser, M. Zaidan, E. Aslangul, M. Saillour, G. Dingulu, F. Chasset, G. Nocturne, X. Mariette, S. Bitoun, R. Seror
Journal: Annals of the Rheumatic Diseases (2024)

<h3>Background:</h3> Anti-Ku are rare antibodies (Ab) directed against heterodimeric DNA-binding proteins and detected in some auto-immune diseases (AIDs). In a first study of 42 anti-Ku positive patients, 2 distinct patterns have been yielded thanks to hierarchical clustering. The 1<sup>st</sup> group corresponded to patients with elevated creatine kinase (CK) levels and an increased risk of interstitial lung disease (ILD); the 2<sup>nd</sup> one included patients carrying anti-dsDNA antibodies with a high risk of glomerulonephritis [1]. Conclusions drawn may be dampened by the limited number of patients and this subgroup of patients remains partially characterized. To explore the role of anti-Ku positivity in patients with AIDs, a larger cohort with longitudinal assessment of the prognosis is therefore valuable to pursue the phenotypic description, to personalize care management, to monitor and prevent long term complications. <h3>Objectives:</h3> Using cluster analysis, we aimed to determine distinct patterns of anti-Ku-positivity in AID patients and their respective prognosis. <h3>Methods:</h3> An observational, multicentric and retrospective study was conducted in 10 University Hospitals in France between January 2010 and March 2022. Inclusion criteria were the positivity of anti-Ku Ab and a suspected AID. We first used an unsupervised multiple correspondence analysis including 19 clinical and biological variables, and then hierarchical clustering to build homogenous clusters of patients. The development of organ involvement throughout the follow-up was also studied. And thereafter, we compared the risk of disease progression, defined as a composite of new organ involvement or by the need for new immunosuppressant, according to each retrieved cluster. This risk was assessed by Cox proportional hazard regression models which estimated hazard ratios (HR) and their 95% confidence intervals (95% CI). <h3>Results:</h3> A total of 154 patients with anti-Ku Ab were included. At baseline, main diagnoses were inflammatory myopathies (IM, n=51/154, 33%), systemic lupus erythematosus (SLE, n=46/154, 30%), Sjögren's disease (SjD, n=30, 19%), systemic sclerosis (SSc, n=27/154, 18%), and rheumatoid arthritis (RA, n=12/154, 7.8%). Hierarchical clustering analyses based on 19 selected variables, which did not include disease classification, identified 3 distinct clusters: i)Cluster 1 (n=42/154, 27%) included a majority of patients with IM (n=35/42, 83%) and/or SSc (n=17/42, 40%). All patients had muscle involvement and 7 had myocarditis. ii)Cluster 2 (n=69/154, 45%) included the lowest proportion of women (68%), a majority of patients displayed ILD (n=31/42, 74%), a quarter of the latter fulfilled SjD criteria. iii)Cluster 3 (n=43/154) included younger patients (median age 25 years, vs 52 in cluster 1 and 55 in cluster 2), and the highest proportion of African (58%) and Asian (16%). Patients mainly displayed SLE features and 79% of them fulfilled SLE criteria. These clusters have distinct outcomes (p=0.0014, Figure 1): the 1<sup>st</sup> cluster mainly developed lung involvement (Figure 2) and displayed a higher risk of disease progression (Figure 1), the 2<sup>nd</sup> subgroup was prone to myositis development (Figure 1 and 2, HR 0.53, 95% CI 0.33-0.84), and the 3<sup>rd</sup> subgroup displayed various clinical manifestations (Figure 2), and had the lowest risk of a new immunosuppressant prescription over time (Figure 1, HR 0.42, 95% CI 0.25-0.69). The proportion of patients with heart involvement almost doubled over time in all clusters (Figure 2). <h3>Conclusion:</h3> Our study delineates 3 phenotypes of patients with anti-Ku Abs: 1/with muscle involvement, 2/with ILD and 3/with SLE features. These clusters had different prognosis and calls for an adapted monitoring and care management of each subgroup of patients. <h3>REFERENCES:</h3> [1] Spielmann, L. et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. <i>Ann Rheum Dis</i><b>78</b>, 1101-1106 (2019). <h3>Acknowledgements:</h3> <b>NIL.</b> <h3>Disclosure of Interests:</h3> Marie Robert: None declared, Yann Nguyen: None declared, Yves Allenbach: None declared, Karim Sacre Novartis, Benjamin Terrier: None declared, Raphael Borie Boehringer Ingelheim, Sanofi and Ferrer, Yurdagul Uzunhan: None declared, Zahir Amoura: None declared, Céline Comparon: None declared, Philippe Dieudé: None declared, Véronique Le Guern: None declared, Capucine Morélot-Panzini: None declared, Marc Humbert: None declared, Olivier Sitbon: None declared, Cécile Goujard: None declared, Brigitte Bader-Meunier: None declared, Bruno Fautrel: None declared, Pascale Chrétien: None declared, Pascale Roland-Nicaise: None declared, Claire Goulvestre: None declared, Jean-Luc Charuel: None declared, Olivier Benveniste: None declared, Luc Mouthon: None declared, Victoire De Lastours: None declared, Perrine Dusser: None declared, Mohamad Zaidan: None declared, Elisabeth Aslangul: None declared, Marie Saillour: None declared, Glory Dingulu: None declared, François Chasset: None declared, Gaetane Nocturne Gaëtane Nocturne received honoraria from Boehringer, Novartis, and travel fees from Amgen, Abbvie., Xavier Mariette Xavier Mariette received consulting fees from Astra Zeneca, Bristol Myer Squib, Galapagos, GSK, Novartis and Pfizer., Samuel Bitoun: None declared, Raphaèle Seror Raphaèle Seror received consulting fees from GSK, Bristol Myer Squib, Boerhinger and Janssen; honoraria from GSK, Bristol Myer Squib, Boehringer, Amgen, Pfizer and Roche; travel fees from Amgen and GSK.