Background/Purpose: The prompt identification of patients with systemic lupus erythematosus (SLE) at risk of or in flare strongly influences the prognosis of the disease. Cell-bound complement activation products (CB-CAPs) have been studied as biomarkers of SLE activity. Despite growing knowledge, experience with CB-CAPs in the Latin American population is scarce. Therefore, this study aims to explore the behavior of CB-CAPs to determine lupus activity in SLE Colombian patients.

Methods: We conducted a cross-sectional study of 30 adult SLE patients (ACR/EULAR 2019 criteria) and 24 technical controls. Subjects were recruited from two centers in Medellín, Colombia, between September 2021 – January 2022. We used the non-serological SELENA/SLEDAI index (SELENA/SLEDAIns) to define activity as follows: inactive (0 points), mild/moderate (1-6 points), and severe (≥7 points) activity. We determined by flow cytometry the median fluorescence intensity (MFI) of the C3d and C4d bound to erythrocytes (E-C3d, E-C4d), reticulocytes (R-C3d, R-C4d), B lymphocytes (B-C3d, B-C4d), T CD4 (TCD4-C3d, TCD4-C4d), and T CD8 (TCD8-C3d, TCD8-C4d) lymphocytes. Descriptive correlations and an exploratory analysis of the accuracy of CB-CAPs to identify severe activity were performed.

Results: Table 1 shows the demographic and clinical characteristics of the SLE patients. Two inactive subjects, 11 with mild disease activity and 17 with severe activity, were included. Table 2 shows correlations between CB-CAPs with anti-dsDNA dilutions and serum complement. There was a statistically significant correlation between clinical SELENA-SLEDAIns with the TCD8-C4d MFI and TCD8-C3d MFI (figure 1). The results showed a negative correlation between C3 levels and SELENA-SLEDAIns for all patients (Rho= -0.57; p=˂0.001) and patients with severe disease activity (Rho= -0.65; p=0.004). In the case of C4, the correlation was -0.51 (p=0.004) for the 30 SLE subjects. Spearman correlation coefficients were not significant between anti-dsDNA by IIF and SELENA/SLEDAIns in none of the groups. The R-C4d had the highest sensitivity (75%), the best specificity (64%), and the area under the ROC curve (0.7 CI 95% 0.53-0.87). Therefore, R-C4d MFI was the CB-CAP with the best performance to discriminate lupus severe activity (SELENA/SLEDAIns ≥7 points).

Conclusion: This is the first time that TCD8-C4d and TCD8-C3d MFI demonstrated significant correlations with lupus disease activity. Previously, T-C4d was correlated with activity in an ethnical minority. To our knowledge, there are no data on this biomarker in large and diverse cohorts, which places a gap in the knowledge and an opportunity for future investigations. As we did, other authors have demonstrated the utility of R-C4d as a lupus disease activity biomarker.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/role-of-cell-bound-complement-fragments-as-biomarkers-to-determine-disease-activity-in-patients-with-systemic-lupus-erythematosus/