Association of autoantibodies against the M2-muscarinic receptor with perinatal outcomes in women with severe preeclampsia

BACKGROUND: The goal of this study was to test the hypothesis that autoantibodies against M(2)-muscarinic acetylcholine receptor (M(2)-AAB) are associated with severe preeclampsia and increased risk of adverse perinatal outcomes. METHODS: We conducted a case–control study comparing 60 women with severe preeclampsia to 60 women with normal pregnancy and 60 non-pregnant controls. A peptide, corresponding to amino acid sequences of the second extracellular loops of the M(2) receptor, was synthesized as antigen to test for the presence of autoantibodies, using an enzyme-linked immunosorbent assay. The frequency and titer of M(2)-AAB were compared in the 3 groups. The risk of adverse perinatal outcomes among women with severe preeclampsia in the presence of M(2)-AAB was estimated. RESULTS: M(2)-AAB were positive in 31.7% (19/60) of patients with severe preeclampsia, in 10.0% (6/60) (p = 0.006) of normal pregnant women and in 8.3% (5/60) (p = 0.002) of non-pregnant controls. The presence of M(2)-AAB was associated with increased risk of adverse pregnancy complications (OR, 3.6; 95%CI, 1.0-12.6; p = 0.048), fetal growth restriction (OR, 6.8; 95% CI, 2.0-23.0; p = 0.002), fetal distress (OR, 6.7; 95% CI, 1.7-26.6; p = 0.007), low Apgar score (OR, 5.3; 95% CI, 1.4-20.7; p = 0.017), and perinatal death (OR, 4.3; 95% CI, 1.0-17.6; p = 0.044) among women with severe preeclampsia. CONCLUSIONS: This study demonstrates, for the first time, an increase in M(2)-AAB in patients with severe preeclampsia. Women with severe preeclampsia who are M(2)-AAB positive are at increased risk for neonatal mortality and morbidity. We posit that M(2)-AAB may be involved in the pathogenesis of severe preeclampsia.