Activation of the Alternative Complement Pathway Accompanies Disease Flares in Systemic Lupus Erythematosus During Pregnancy

Abstract

Objective. To assess the activity of systemic lupus erythematosus (SLE) during pregnancy and to distinguish it from preeclampsia.Methods. We prospectively measured the complement activation products Ba, Bb, SC5b-9, and C4d, as well as the conventional complement determinants C3, C4, and CH50, during pregnancy in 14 patients with SLE and 10 women with preeclampsia.Results. Four of the 14 SLE patients were considered to have disease flares, 3 occurring in the second trimester and 1 postpartum. In these patients, significant abnormalities of Ba, Bb, SC5b-9, and CH50 were noted. In contrast, measures of C4d did not distinguish between pregnant patients who had flares and those whose SLE remained stable. Although decreased values of C3 were rarely seen in the patients with stable disease, normal values of C3 during lupus pregnancy were not reliably associated with stable disease. Three of Submitted for publication January 17, 1991; accepted in revised form August 12, 1991.10 non-SLE patients with preeclampsia had elevated levels of Ba; however, in each case, the CH50 level was close to or within the normal range. This was in sharp contrast to the findings observed in the 4 patients with active SLE, in whom high levels of plasma Ba were always associated with low CH50 values. Moreover, the ratio of CH50 to Ba was significantly lower in the patients with lupus flares than in the non-SLE patients with preeclampsia.Conclusion. While a decline in the C W O level alone could otherwise be attributed to decreased synthesis of complement components, these data demonstrate that ongoing activation of the alternative complement pathway can accompany disease flares in pregnant women with SLE.

The correlation of pregnancy complications with C3/C4 levels, anti-dsDNA titers, and autoimmune target testing in gravidas with systemic lupus erythematosus

“…C3 and C4 may be decreased with increased lupus activity because these proteins are consumed in the inflammatory process [31]. In pregnancy, however, the complement levels may increase 10-50% in response to increased hepatic protein synthesis [32]. During pregnancy, C3 and C4 may rise to supranormal levels, and thus a flare with complement activation may occur despite apparently normal levels of C3 and C4.…”

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

“…Measurement of complement split products may be most helpful in situations in which conventional measurements are not, such as in lupus patients who are pregnant. In a recent study by Buyon and colleagues (37), the combined evaluation of conventional measurements (C3, C4) and complement split products was the most useful in differentiating active lupus nephritis from preeclampsia in pregnant women with SLE. In addition, complement split product determinations may have a role in patients with chronically low levels of C3 or C4, or those whose C3 and C4 levels remain normal despite clinical evidence of disease activity.…”

Lupus Activity in Pregnancy

“…37 In pregnancy, however, the complement levels may increase 10-50% in response to increased hepatic protein synthesis. 38 Therefore, the utility of complement measurement in pregnancy is unclear. In the Hopkins Lupus Pregnancy Cohort, half of the pregnancies had hypocomplementemia at some point.…”