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Objectives To evaluate the serological evolution of patients with systemic lupus erythematosus (SLE), focusing on the appearance or modification of existing autoantibodies.Methods A retrospective study was conducted on 82 SLE patients treated at a general hospital in northern Spain. Demographic data, clinical features, comorbidities, treatments, and both baseline and follow-up immunological profiles were collected. Autoantibodies evaluated included ANA, anti-dsDNA, anti-Ro/SSa (52 kDa and 60 kDa), anti-La/SSb, anti-Sm, anti-RNP, and antiphospholipid antibodies (aCL, aB2GPI, lupus anticoagulant). Patients were classified into four serological clusters based on the RELESSER registry: (1) Absence of ENA antibodies, (2) aPL positivity, (3) anti-SSa/SSb positivity, (4) anti-Sm or anti-RNP positivity. Changes in autoantibody status were categorized as persistent, transient, or negative/positive conversions based on predefined criteriaResults Among the 82 patients (90% women, 91% Caucasian), common manifestations included hematological involvement (72%) and arthritis (57%). ANA was positive in 95% of cases. The most frequent specific autoantibodies were anti-Ro (34%) and anti-dsDNA (23%). aCL and aB2GPI antibodies were detected in 38% and 32% of patients, respectively. Patients were distributed among the clusters defined as follows: Cluster 1: 23 patients (28%), cluster 2: 19 patients (23%) cluster 3: 17 patients (21%) and Cluster 4: 10 patients (12%) The average follow-up was 169.6 ± 108.3 months, with a mean of 2.5 ENA and 2.2 aPL determinations per patient.Serological evolution data was available for 66 patients. Only 9 patients (14%) changed their serological cluster during follow-up. Most changes (7/9) did not alter cluster assignment. Changes included new positivity or loss of anti-RNP, anti-Sm, anti-Ro, and anti-La. Twenty-two changes were detected in aPL profiles: 3 patients became persistently negative, 2 persistently positive, and 12 showed transient positivity.Conclusions Our findings support that serological profiles in SLE are largely stable over time. Only a minority of patients experienced significant changes in autoantibody expression affecting cluster classification. These results reinforce the clinical relevance of baseline serological profiling for prognostic and therapeutic decision-making