Autoantibody Clusters in Childhood-onset Systemic Lupus Erythematosus: Insights from a Multicenter Study with 912 Patients

To identify clusters of autoantibodies in a large cSLE population and to verify possible associations between different autoantibody clusters and the following variables: demographic data, cumulative clinical and laboratory manifestations, disease activity, cumulative damage and mortality. A cross-sectional study was performed in 27 Pediatric Rheumatology University centers, including 912 cSLE patients. The frequencies of seven selected autoantibodies (anti-dsDNA, anti-Ro/SSA, anti-La/SSB, anti-Sm, anti-RNP, aCL IgM and/or IgG and LA) were used for cluster analysis using the K-means method. Four distinctive antibody clusters were identified. Cluster 1 ( = 322; 35.31%) was characterized by anti-dsDNA (61.18%), low frequency of antiphospholipid antibodies (<10%), and lower frequency of cutaneous, articular manifestation ( < 0.05) and hypocomplementemia ( < 0.001) compared to the other groups. Cluster 2 ( = 158; 17.32%) comprised anti-dsDNA (93.04%), aCL (87.34%) and LA (39.87%) and higher frequencies of thrombocytopenia ( = 0.006) and antiphospholipid syndrome ( < 0.001) than the other clusters. Cluster 3 ( = 177; 19.41%) was characterized by anti-dsDNA (81.36%), anti-Sm (100%) and anti-RNP (44.63%) antibodies, as well as a higher frequency of proteinuria compared to cluster 4 (58.15% vs 56.13% vs 64.00% vs 49.80%, = 0.031). Cluster 4 ( = 255; 27.96%) consisted of all 7 autoantibodies, with predominance of anti-dsDNA (72.55%), anti-Ro/SSA (89.8%) and anti-La/SSB (45.88%), with no specific clinical pattern, except by higher pulmonary damage ( = 0.017). Our study suggests that, within the context of cSLE, the coexistence of anti-dsDNA with antiphospholipid autoantibodies is linked to an elevated incidence of antiphospholipid syndrome. This association does not coincide with a proportionate increase in the occurrence of nephritis. Conversely, the cluster of anti-dsDNA with anti-Ro/SSA and anti-La/SSB antibodies was associated with pulmonary damage, requiring close surveillance.