First‐trimester serum BAFF:sFlt‐1 ratio as a candidate early biomarker of spontaneous abortion

Abstract

Problem Immunologic, angiogenic, and anti‐angiogenic factors are associated with spontaneous abortion (SAB). B cell–activating factor (BAFF), a proliferation‐inducing ligand (APRIL), placental growth factor (PlGF), and soluble fms‐like tyrosine kinase‐1 (sFlt‐1) may play a role in SAB and may serve singly or in combination as an early biomarker of SAB. Method of Study In this prospective observational study, serum sFlt‐1, PIGF, BAFF, and APRIL levels were measured in the first trimester of pregnancy in a medically diverse group of women and in non‐pregnant controls. Associations and discriminative values of first‐trimester sFlt‐1, PIGF, BAFF, and APRIL levels and the corresponding APRIL:BAFF, BAFF:sFlt‐1, and sFlt‐1:PlGF ratios with development of SAB were tested. Results Median serum BAFF level was lower (p = .007) and median serum sFlt‐1 level was higher (p < .001), in the first trimester of pregnancy than in non‐pregnant controls. SAB developed in 27 of the pregnant women (11.3%), and first‐trimester levels of BAFF (but not APRIL) and sFlt‐1 (but not PIGF) were associated with SAB. Using optimal cutoffs determined through receiver operating characteristics curves, the best discriminator of SAB was the serum BAFF:sFlt‐1 ratio, specifically among non‐nulliparous women and women with prior SAB. Conclusion First‐trimester serum BAFF:sFlt‐1 ratio is a candidate indicator/predictor of SAB among non‐nulliparous women and women with prior SAB. If validated through additional studies, then early identification of pregnant women at high risk for SAB through this simple blood test would assist in counseling and facilitate clinical trials of therapeutic interventions.

Maternal and cord blood BAFF and APRIL levels during pregnancy

“…Sera were routinely isolated from the clotted blood samples within 12 to 24 h and were aliquoted and stored at −80°C for subsequent batch analysis. Serum levels of BAFF and APRIL were measured in duplicate in a blinded fashion by ELISA 7,8 …”

“…Indeed, we have previously reported that increased maternal first‐trimester levels of BAFF in women without any known chronic medical disease may be an early and clinically useful predictor of hypertensive disorders of pregnancy 7 . Moreover, maternal first‐trimester levels of BAFF were greater in women who underwent a spontaneous abortion than in those who maintained their pregnancies 8 …”

“…7 Moreover, maternal first-trimester levels of BAFF were greater in women who underwent a spontaneous abortion than in those who maintained their pregnancies. 8 A factor closely related to BAFF is a proliferation-inducing ligand (APRIL) which serves as a vital survival factor for plasma cells. 9 Given the structural homology between BAFF and APRIL and their sharing two receptors (BCMA and TACI), [10][11][12][13] we reasoned that maternal APRIL levels during the course of pregnancy could also be informative with regard to pregnancy outcomes.…”

“…• C for subsequent batch analysis. Serum levels of BAFF and APRIL were measured in duplicate in a blinded fashion by ELISA 7,8. 2.analyses were performed using SigmaStat software (SPSS) or Medcalc software (www.medcalc.org).…”

B-Cells and BAFF in Primary Antiphospholipid Syndrome, Targets for Therapy?

“…One study specifically studied pregnant patients with obstetric PAPS and found higher levels of BAFF as compared to healthy pregnant women, particularly in those with prior adverse pregnancy events [59]. Notably, BAFF levels were lower in healthy pregnant subjects as compared with non-pregnant healthy subjects, suggesting a drop in BAFF levels during normal pregnancy [59,60]. The levels of BAFF in the pregnant obstetric PAPS patients were similar as in healthy, non-pregnant subjects [59] although pre-and post-pregnancy samples were not collected in the obstetric APS patients.…”