Background/Purpose: We reported (Ramsey-Goldman et al., Arthritis Rheumatol 2018: 70 [suppl 10]) that cell-bound complement activation products (CB-CAPs) and a multi-analyte assay panel with algorithm (MAP) are positive more frequently than standard immunological markers in patients with probable systemic lupus erythematosus (pSLE) who fulfilled 3 ACR criteria. We followed pSLE prospectively to evaluate whether CB-CAPs and MAP positivity at enrollment predict transition to classifiable SLE by fulfillment of a fourth ACR criterion.

Methods: pSLE were followed prospectively at academic lupus centers and clinical and laboratory data were collected. Biomarkers were measured at every visit. CB-CAPs – C4d bound to erythrocytes (EC4d) and B-cells (BC4d) – were measured by quantitative flow cytometry and expressed as mean fluorescent intensity (MFI). Serum C3 and C4 and autoantibodies were measured by turbidimetry and ELISA, respectively. Anti-dsDNA positivity was confirmed by immunofluorescence (IFA) with Crithidia Luciliae. MAP was evaluated as previously described (Dervieux T, et al. J Immunol Methods 2017) and consists of an algorithm which utilizes CB-CAPs and autoantibodies. A MAP score >0.1 is considered positive, the higher the number (to 3.5) the greater the likelihood of SLE. For this study, decision analysis with Youden index showed that MAP >0.8 and EC4d >20 MFI reflected the optimal cutoff. Data were analyzed by Fisher’s exact test and Kaplan-Meier with log-rank test and Cox proportional hazards model for time to fulfillment of a fourth ACR criterion, expressed as hazard ratios.

Results: Of the 92 pSLE enrolled, 69 had 1 follow up visit 9-18 months after enrollment (average±SD = 12.4±1.7 months; median = 12 months). The time to acquire the 4th ACR criterion was estimated by the investigators at the follow up visit. Twenty pSLE (29%) fulfilled a fourth ACR criterion during this time. SLICC fulfillment at enrollment did not predict fulfillment of ACR criteria (p =0.27). Eight of the 20 (40%) pSLE who transitioned to classifiable SLE by ACR criteria had MAP >0.8 at enrollment while 8/48 (17%) non-transitioned patients had MAP > 0.8 at enrollment (p =0.06). Patients with MAP >0.8 at enrollment fulfilled ACR criteria with a hazard ratio (HR) =3.11 within 18 months (p < 0.01 by log-rank test). HR of MAP was higher than other individual biomarkers, although anti-dsDNA and EC4d >20 MFI were of borderline significance (Table).

Conclusion: Complement activation as detected by MAP >0.8 at enrollment may predict disease evolution of pSLE into classifiable SLE by ACR criteria better than anti-dsDNA and low serum complement.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/complement-activation-in-probable-systemic-lupus-erythematosus-psle-may-predict-progression-to-sle-defined-by-fulfillment-of-acr-classification-criteria/