Background/Purpose:

The onset of SLE, a prototypical autoimmune disease characterized by immune dysregulation and consequential inflammatory tissue injury, may be insidious with non-specific symptoms. The current standard for diagnosing SLE is based on the ACR classification criteria. A diagnosis of definite SLE is made when a patient has met 4 of the 11 criteria, which may take years to fulfill. Patients who have met less than 4 ACR criteria may have pre-SLE and may go on to develop definite SLE, in whom serious organ damages might have occurred unnecessarily due to the missed opportunity of early treatment. Our recent studies have shown that cell-bound complement activation products (CB-CAP), particularly cell-bound C4d, can serve as unique biomarkers not only for diagnosis but also for disease activity monitoring in patients with SLE. We hypothesize that profiling the CB-CAP patterns in patients at risk for developing SLE may provide a “window” that may allow physicians to identify patients at an early stage of SLE and institute appropriate treatment accordingly.

Methods: To verify this hypothesis, a cross-sectional study investigating C4d levels on various circulating cells was conducted using blood samples taken from 429 patients with definite SLE, 51 patients with pre-SLE, 285 patients with other immune-inflammatory diseases, and 196 healthy individuals. Seven circulating cell types, including erythrocytes, reticulocytes, platelets, T and B lymphocytes, monocytes, and granulocytes, were detected and analyzed for surface-bound C4d by flow cytometry. Cell-bound C4d measure on each cell type was also classified in a binary positive (score = 1) and negative (score = 0) fashion and a cumulative CB-C4d score (ranging from 0 to 7) was derived for each study subject.

Results:

The results showed that C4d levels on all 7 circulating cell types were significantly elevated in patients with definite SLE or pre-SLE, compared to patients with other immune-inflammatory diseases, and healthy controls. However, the CB-C4d levels, with the exception for T cell- and B cell-bound C4d, were statistically indistinguishable between patients with definite SLE and patients with pre-SLE. When the cumulative CB-C4d scores of individual patients were calculated and compared, patients with definite SLE and pre-SLE were inclined to accrue higher CB-CAP scores (with an average score of 2.44 and 2.12, respectively) than did patients with other immune-inflammatory diseases (average score 0.72). Moreover, high CB-C4d scores were more prevalent in patients with definite SLE and pre-SLE than in patients with other immune-inflammatory diseases. The frequency distribution of CB-C4d scores within the patient group of pre-SLE resembled that within the patient group of definite SLE, but was considerably different from that within the patient group of other diseases.

Conclusion:

Collectively, the results suggest that CB-CAP generation may occur early during the pathogenic process of SLE. CB-CAP profiling may help identify patients at risk for developing full-blown SLE and thus provide preventative care to minimize disease progression.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/cell-bound-complement-activation-products-cb-cap-profiles-in-patients-with-pre-systemic-lupus-erythematosus/