Sequential Studies of Complement Activation in Systemic Lupus Erythematosus

Abstract

C1 and C3 activation, measured as C1r-C1s-C1 inactivator C1s-C1r-C1IA complexes in serum and circulating C3d were studied in serial samples from 33 patients with SLE. All patients demonstrated exacerbations during observation periods of 10-30 months and were divided into groups according to principal clincal features (mild SLE, severe extra-renal SLE, and lupus glomerulonephritis). Increased C1 activation was consistently found during exacerbation. C3d in plasma was a feature associated with severe disease flares. Activation of C1, but not of C3, was documented before flare-ups of disease activity, but such predictive information was mostly restricted to patients with extra-renal disease. C2 cleavage in plasma, studied serially in a few patients, appeared to be closely associated with C1 activation. Circulating immune complexes, measured with solid-phase C1q assay, did not always increase before development of clinical manifestations. Remission of symptoms was paralleled by decreasing concentrations of C1r-C1s-C1IA and of, when present, C3d. Similar findings were made for immune complexes but only in severe disease. Persisting C3d was observed in 3 patients, who subsequently developed renal failure. C1q levels were transiently low during flare-ups of lupus glomerulonephritis, but otherwise the concentrations of C1q, C4 and C3 did not show consistent patterns of variation in relation to disease activity.

Laboratory tests as predictors of disease exacerbations in systemic lupus erythematosus. Why some tests fail

“…In contrast, Sturfelt et a1 (15) found that changes in levels of C4 and C3, and solid-phase Clq binding did not predict 8 renal and 16 nonrenal flares. Buyon et al (19) also found conventional measures of complement (C4, C3, and CH50) to be of limited value in predicting 8 renal and 14 nonrenal flares.…”

“…Thus, tests for levels of complement split products, interleukin-2 receptor, and urinary free light chains, among other tests, have been reported to predict subsequent disease activity in recent studies (15)(16)(17)(18)(19). While they are of considerable interest for understanding the pathogenesis of SLE, these tests are not routinely available.…”

Annexin A2 and A5 Serve as New Ligands for C1q on Apoptotic Cells

“…Clearly, C1q has many functions crucial for homeostasis and prevention of SLE. Accordingly, low serum levels of C1q correlates with severe active SLE (51).…”

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

“…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).…”