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)

CÉLIA DOS SANTOS; GUSTAVO GRELONI; MARÍA F ALBERTO; ANALÍA SÁNCHEZ-LUCEROS

Philadelphia

Congreso; ISTH 2021 Virtual congress; 2021

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