Increased levels of plasma anaphylatoxins in systemic lupus erythematosus predict flares of the disease and may elicit vascular injury in lupus cerebritis

Abstract

We measured levels of complement anaphylatoxin split products, C3a and C5a, in the circulation of patients with systemic lupus erythematosus (SLE). In 23 SLE patients who were followed serially, the mean C3a value was 179 ng/ml during stable disease and 550 ng/ml during a disease flare. In 10 patients, C3a levels predicted disease activity, with the C3a value rising from a mean of 183 ng/ml at a time of stable disease to a mean of 242 ng/ml 1-2 months prior to a clinical exacerbation of disease. The mean C3a level in 5 patients with acute dysfunction of the central nervous system (CNS) was 1,297 ng/ml, which is significantly higher than that observed in patients with active disease but without CNS involvement (P < 0.01). C5a levels were also significantly elevated in 4 patients with acute CNS disease. Pathologic specimens from 2 patients who died during an acute lupus flare revealed neutrophils occluding the cerebral and intestinal vessels. Fluorescein angiography in a patient with CNS lupus revealed vasoocclusive retinopathy. In 5 of 7 SLE patients who were pregnant, C3a levels were elevated, with a group mean value of 310 ng/ml. There was a negative correlation (r = -0.59) between C3a and C3 levels in pregnant patients with SLE, and this finding is consistent with comple-~~

Reticulocytes bearing C4d as biomarkers of disease activity for systemic lupus erythematosus

“…Second, serum C3 and serum C4 have been widely used in attempts to monitor disease activity in SLE. Although the utility of these measurements is a subject of controversy, it is generally held that in some patients, particularly those with lupus nephritis, these are useful tests (3)(4)(5)10,13,14). Surprisingly, these tests have not been replaced or improved upon despite enormous advances in our understanding of complement biology during the last 20 years.…”

“…Although serum levels of C3, C4, and their activation-derived products are frequently used to monitor disease activity in SLE, their value as biomark-ers is a subject of controversy (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). These observations have led us to consider measurement of complement activation products bound to circulating blood cells (14,15).…”

Sensitivity and specificity of plasma and urine complement split products as indicators of lupus disease activity

“…Fewer studies have actually addressed the predictive value of complement activation products (1,6). Hopkins and colleagues (6) reported that a rise in the C3a level at a time of stable disease predicted a disease flare 1-2 months later, in 10 patients who were followed up prospectively. In contrast, a fall in the C3 level occurred in only 7 of the 10 patients who had a subsequent disease flare, with the C3 value falling below the normal range in only 2 patients.…”

Complement-Dependent Apoptosis and Inflammatory Gene Changes in Murine Lupus Cerebritis

“…In addition, systemic complement activation, as reflected by increased serum levels of the anaphylatoxins, C3a and C5a, has been shown to correlate with CNS disease (12). Once complement activation occurs, it can lead to increased migration of cells toward the site of inflammation, alter the release of cytokines, and cause cell necrosis or apoptosis (3,13,14).…”