Introduction Cell-bound complement activation products (CB-CAPs) in a multi-analyte assay with algorithm (MAP) is a valuable biomarker for the diagnosis of SLE. Erythrocyte-bound complement activation products have been associated with SLE disease activity. The clinical and serologic phenotype of longitudinal MAP positive patients has not been well described. Herein, we evaluated the relationship between longitudinal MAP results with clinical and laboratory variables.

Methods This was a longitudinal study of adult SLE patients (2012 SLICC or 2019 ACR/EULAR criteria with a range of disease activity) with ≥2 routine lupus clinic visits from June 2020 to July 2022. Patients completed the polysymptomatic distress scale. The treating rheumatologist scored the PGA and SLEDAI scores at the time of the visit. Autoantibodies including ANA and anti-RNA-binding proteins were measured by ELISA. Anti-dsDNA was determined by immunofluorescence using the Crithidia luciliea assays. CB-CAPs were analyzed by flow cytometry. The multi-analyte assay panel (MAP) was determined using a 2-tier algorithm. Chi- square and ANOVA tests were used to analyze differences in demographic and disease history between persistently MAP positive, MAP negative, and patients with changing MAP positivity. Serologies and clinical variables at follow-up visits were compared using generalized linear models.

Results In this longitudinal cohort of 113 patients with 175 follow-up visits (100% SLICC SLE, 90% female, 62% Black, mean age 45) 65% were consistently MAP positive, 20% were negative, and MAP positivity changed in 15%. Patients with persistent MAP positivity were younger and more often of Black race. There was no difference in MAP positivity based on SLE disease duration. Significantly more MAP positive patients met 2019 ACR/EULAR criteria and had higher total ACR/EULAR scores. Patients who remained MAP positive were more likely to have a history of acute cutaneous lupus but there was no difference in other historical manifestations of SLE between the three groups (table 1).

When evaluating longitudinal associations, patients with persistent MAP positivity had higher total SLEDAI scores, but there was no difference in the clinical SLEDAI. Therapy was comparable across groups except for greater use of belimumab, rituximab, and cyclophosphamide in persistent MAP-positive patients. Patients who remained MAP positive reported higher rates of depression, but a similar amount of polysymptomatic distress and fatigue. A greater number of lupus-specific serologies were present in those with MAP positivity (table 2).

Conclusion Identifying endotypes of SLE is important to advancing personalized medicine. In this longitudinal cohort of SLE with a full spectrum of disease active, MAP results were static in most patients. MAP resulted changed between visits in a subset of patients; although there was not a distinct clinical, demographic or laboratory phenotype in those patients. Patients with consistent MAP positivity reported more depression and had a greater burden of disease activity as measured by the ACR/EULAR score and greater use of biologic and cytotoxic therapy. Combining longitudinal MAP scores with traditional assessment of SLE assessments activity may provide useful prognostic information and allow identification of a higher risk cohort of patients. Larger longitudinal studies are on-going to evaluate the relationship between individual CB-CAPs and markers of disease activity.