Cell-bound complement biomarkers for systemic lupus erythematosus: from benchtop to bedside

Abstract

Systemic lupus erythematosus is arguably the most clinically and serologically diverse autoimmune disease. This article highlights the biomarkers helpful in diagnosing this disease. The authors' own research is presented.

Figure 1. Schematic summary of the rationale and methodology of the CB-CAP biomarkers

(A) Rationale: During SLE flares, considerable amounts of complement activation products may be generated. These CAPs may bind stably to various circulating cells in proportion to the extent of complement activation. (B) Schematic illustration of the multicolor staining of circulating cells for cell type-specific surface markers and surface-bound CAPs (e.g., C4d). (C) Representative dotplots demonstrate the identification of erythrocytes, reticulocytes, platelets, lymphocytes, monocytes, and granulocytes. These cell types can also be differentiated using cell lineage-specific mAbs added to the cell suspension (e.g., anti-CD3, anti-CD19, etc).

Figure 2. The “Erythrocyte Time Capsules” model

(A) Schematic illustration of the hypothetical model; (B) Histograms of E-C4d levels on age-fractionated erythrocytes prepared from a representative SLE patient. The open histograms represent the C4d staining on the entire population (left panel) or density/age-fractionated erythroctyes (right panel). The purple closed peak depicts the background staining of erythrocytes using an istotype mouse IgG control.