Platelet C4d is highly specific for systemic lupus erythematosus

Abstract

Objective. Complement-activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet-bound C4d may provide a biomarker for SLE.Methods. We conducted a cross-sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d.Results. Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P ‫؍‬ 0.035) or the IgM (P ‫؍‬ 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P ‫؍‬ 0.039), low serum C4 (P ‫؍‬ 0.046), an elevated erythrocyte sedimentation rate (P ‫؍‬ 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001).Conclusion. This observation suggests that platelet-bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies.

Platelet C4d Is Associated With Acute Ischemic Stroke and Stroke Severity

“…Platelet C4d was detected as previously described. 1 Briefly, whole blood was incubated with mouse monoclonal antihuman C4d antibody (Quidel Corporation) or a mouse IgG1k isotype control (Becton Dickinson) that was labeled with Alexa Fluor 488 using a mouse IgG1 Zenon labeling kit (Molecular Probes). The blood was then diluted and analyzed immediately by flow cytometry.…”

Platelet Mediated Complement Activation

“…C4 fragments have been detected on platelets from a subset of patients with systemic lupus erythematosus (SLE), and this correlated with a history of neurologic events and the presence of antiphospholipid antibodies (Navratil, Manzi, Kao, Krishnaswami, Liu, Ruffing, Shaw, Nilson, Dryden, Johnson, and Ahearn 2006). These observations are consistent with preliminary data from our laboratory which suggest a statistically significant correlation between classical complement pathway C1q and C4d deposition on platelets and arterial thrombosis in SLE patients with anti phospholipid antibody syndrome (APS) (Peerschke, Yin, Alpert, Salmon, Roubey and Ghebrehiwet 2007).…”

The Important Roles of C4d in Systemic Lupus Erythematosus

“…Level of platelet-bound C4d (P-C4d) was found to be highly specific for SLE and significantly associated with positivity for lupus anticoagulant and anticardiolipid antibodies. P-C4d was also associated with SLEDAI [25]. Increased complement deposition on platelets was observed in SLE patients with a history of venous thrombosis compared to those without.…”

“…Peripheral free C4d Plasma Monitor disease activity; predict disease flare [12,13] Serum Monitor disease activity [14] Plasma No correlation with SLE during pregnancy [15] C4d binding to blood cells E-C4d Diagnose SLE; monitor disease activity [18,20,31] R-C4d Monitor disease activity [24] P-C4d Diagnose SLE; monitor disease activity; marker for venous thrombosis in SLE; associated with all-cause mortality and ischemic stroke [25][26][27][28] T/B-C4d Diagnose SLE; monitor disease activity [29][30][31] C4d deposition in tissues…”