Serological clusters in systemic lupus erythematosus and its clinical and prognostic implications: A longitudinal...

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by multi-organ involvement and variable clinical manifestations. Recurrent clinical patterns suggest distinct phenotypes, where cluster analysis of autoantibodies could identify prognostic subtypes.

To define and describe serological clusters and their clinical-epidemiological characteristics, as well as their association with comorbidities, disease activity measures, severity, and damage.

Descriptive, observational, and multicenter study including SLE patients from the Spanish Registry RELESSER. Gower distance was used for cluster analysis.

A total of 1,740 patients from the cross-sectional phase and 718 from the prospective phase with a four-year follow-up were included. Four serological clusters were identified. Cluster 1 (negative for extractable nuclear antigen [ENA]) was characterized by a lower frequency of vasculitis, leukopenia, and lymphopenia. Cluster 2 (positive antiphospholipid antibodies) more frequently presented haemolytic anaemia, thrombocytopenia, vasculitis and visual alterations and required greater use of immunoglobulins and oral anticoagulants. Cluster 3 (positive anti-SSA/Ro and anti-SSB/La) had a lower incidence of lupus nephritis. Cluster 4 (positive anti-Sm and anti-ribonucleoproteins) was characterized by higher rates of lupus nephritis, leukopenia, lymphopenia, hypocomplementemia, myositis and cutaneous manifestations and greater use of glucocorticoids and immunosuppressants. Patients in cluster 2 had higher baseline damage scores measured by the SLICC/ACR DI (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), while patients in cluster 4 had higher severity scores measured by the Katz Index. These differences among clusters persisted over the four-year of follow-up.

In our SLE patient population, the serological profile is key not only for clinical stratification but also for prognostic value.