Background: Complications of pregnancy in women with aHUS include preeclampsia. This case study is a 35-year-old carrier of genetic complement anomalies, with GMNC3 and aHUS diagnosis, currently treated with eculizumab (1200 mg/two weeks).

Aims: To monitor clinical and laboratory parameters of the patient during her second pregnancy.

Methods: Routine laboratory and complement testing (ELISA) were performed: (i) total complement activity (IMTEC, Human Diagnostics), (ii) plasmatic sC5b-9 (BD biosciences) and (iii) C5b-9 formation on endothelial cell line HMEC-1 in presence of human serum (home-made cell-based ELISA).

Results: At 24 weeks (w) of gestation, signs of hypertensive crisis included headaches and vomiting for which magnesium sulfate was administered. Between 36-37w, patient suffered nauseas, headaches and blurred vision, and delivered a healthy live birth (2.630kg) following caesarean section. Eculizumab treatment was associated with low levels of total complement activation (≤20U/mL) during pre- and post-natal period. Interestingly, plasmatic sC5b-9 increased significantly between 32w of gestation and first week puerperium (fig 1). However, eculizumab administration (900 mg) was given weekly during first month postpartum (fig 1). 

Timeline of soluble C5b-9 levels in patient plasma during her pregnancy and postpartum. Eculizumab (ECU) dosing regimen was indicated by asterisk (*) or black arrow.

Additionally, we quantified complement activation on HMEC-1 surface induced by cell incubation with patient serum. C5b-9 formation on HMEC-1 was significantly higher in presence of serum from pregnant patient compared with serum from patient postpartum (fig 2A). Complex formation of C5b-9 during puerperium was similar to complex formed with a pooled human serum from 42 healthy donors (PS). Heat-inactivated (HI) serum at 56°C from 34w of gestation, corresponding to peak levels of plasmatic sC5b-9, showed remnant complement activation on HMEC-1, whereas HI PS demonstrated complement inhibition (fig 2B). 

Detection of C5b-9 complex formation on endotelial cell line HMEC-1 using a cell-based ELISA assay. A. Serum from patient during her pregnancy and postpartum as well as from pooled human donors (PS) were incubated with HMEC-1 and complement membrane attack complex was detected using an anti-human C5b-9 antibody. **p<0.01 by Student's t-test. B. Serum from pooled human donors (PS) and from patient at 34 weeks gestation were heat-inactivated at 56⁰C during 1 hour before incubation on HMEC-1 for detection of C5b-9 on cell surface. w: weeks, OD: optical density. *p<0.05 and ***p<0.001 by Student's t-test.

 

Conclusions: Observations from this aHUS case study suggest that monitoring levels of sC5b-9 during pregnancy could offer insight in dose adjustment of anti-C5 therapy. Further studies are needed to explore other pathological pathway mechanisms involved in C5b-9 complex formation on cell surface during pregnancy.

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ISTH Congress Abstracts - https://abstracts.isth.org/abstract/role-of-soluble-c5b-9-sc5b-9-in-dosing-adjustments-of-anti-complement-therapy-during-pregnancy-in-a-patient-with-history-of-atypical-hemolytic-uremic-syndrome-ahus/