ANTI-Ku ANTIBODY SYNDROME: IS IT A DISTINCT CLINICAL ENTITY? A CLUSTER ANALYSIS OF 75 PATIENTS.

Background: Anti-Ku antibodies are rare among patients with Connective Tissue Diseases (CTD) (1). Their potential role as a disease biomarker is not well established. Objectives: To identify subgroups of anti-Ku positive patients according to their spectrum of anti-nuclear antibody (ANA) specificities and analyze their clinical and analytical features. Methods: Multicenter, cross-sectional study of anti-Ku positive patients, irrespective of their diagnosis, followed at eight Rheumatology outpatient clinics. Patients were spontaneously identified according to the local work-out for suspected autoimmune diseases. Anti-Ku and other ANA specificities were determined at each hospital’s Immunology lab according to the local methodology and strategy to decide on which auto-antibodies to check when faced with a positive ANA immunofluorescence. Clinical, analytical and treatment cumulative features were identified following a dedicated structured questionnaire. Hierarchical cluster analysis (method: between-groups linkage, squared Euclidian distance) for ANA specificity variables was performed to identify subgroups. Results: Seventy-five anti-Ku positive patients were included (female: 73.3%, mean age at diagnosis: 50.5±17.9 years, mean disease duration: 4.7±5.4 years). Their clinical diagnosis were undifferentiated connective tissue disease (UCTD) (21.3%), systemic lupus erythematosus (17.3%), Sjögren’s syndrome (16.0%), inflammatory myositis (14.7%), systemic sclerosis (10.7%), overlap CTD syndrome (8.0%), other connective tissue diseases (17.3%), healthy anti-Ku carrier (17.3%). Six autoantibody clusters were identified and included most patients ( Figure 1 ): Cluster 1 - anti-Ku without any other ANA specificities (36.0%); cluster 2 - Anti-nor90 and anti-fibrillarin (8.0%); cluster 3 - anti-Jo1, PL-7, PL-12, and PM-Scl100 (9.3%); cluster 4 - anti-Scl70 (4.0%); cluster 5 - anti-Sm, anti-ribosome, and anti-dsDNA (13.3%); cluster 6 - anti-centromere, Th/To, PM-Scl75 (8.0%). The remaining patients were outliers (21.3%) not fitting in any cluster. Figure 1. Hierarchical cluster analysis of ANA specificities in anti-Ku+ patients Detailed clinical analysis of patients in cluster 1, the most numerous, presenting anti-Ku antibodies without any other ANA specificities, the most frequent clinical manifestations were: Raynaud’s phenomenon (40.7%), arthritis (25.9%), sicca syndrome (25.9%), myositis (14.8%), and interstitial lung disease (ILD) (14.8%); 25.9% were healthy anti-Ku carriers. Patients from cluster 1 were most frequently treated with low dose glucocorticoids (51.9%), hydroxychloroquine (37.0%), or methotrexate (18.5%). Among the whole study population (n=75), major organ involvement was present in 18.7%, with ILD in 10.7% and renal involvement in 8.0%. None of the patients in cluster 1 presented nephritis. Conclusion: Anti-Ku positive patients without any other ANA specificities is the largest subset and may represent a distinct entity among the differentiated CTD (2). Patients with this anti-Ku syndrome may develop ILD. In addition, anti-Ku antibodies can be found in patients with a diversity of other ANA specificities and heterogeneous CTD diagnosis. REFERENCES: [1]Lakota K, et al. International cohort study of 73 anti-Ku-positive patients: association of p70/p80 anti-Ku antibodies with joint/bone features and differentiation of disease populations by using principal-components analysis. Arthritis Res Ther. 2012 Jan 6;14(1):R2. doi: 10.1186/ar3550. PMID: 22226402; PMCID: PMC3392788. [2]Spielmann L, et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Ann Rheum Dis. 2019 Aug;78(8):1101-1106. doi: 10.1136/annrheumdis-2018-214439. Epub 2019 May 24. PMID: 31126956. Disclosure of Interests: None declared Citation: , volume 81, supplement 1, year 2022, page 724Session: Scleroderma, myositis and related syndromes (POSTERS only)