Synapsin autoantibodies during pregnancy are associated with fetal abnormalities.

Anti-neuronal autoantibodies can be transplacentally transferred during pregnancy and may cause detrimental effects on fetal development. It is unclear whether autoantibodies against synapsin-I, one of the most abundant synaptic proteins, are associated with developmental abnormalities in humans. We recruited a cohort of 263 pregnant women and detected serum synapsin-I IgG autoantibodies in 13.3% using cell-based assays. Seropositivity was strongly associated with abnormalities of fetal development including structural defects, intrauterine growth retardation, amniotic fluid disorders and neuropsychiatric developmental diseases in previous children (odds ratios of 3-6.5). Autoantibodies reached the fetal circulation and were mainly of IgG1/IgG3 subclasses. They bound to conformational and linear synapsin-I epitopes, five distinct epitopes were identified using peptide microarrays. The findings indicate that synapsin-I autoantibodies may be clinically useful biomarkers or even directly participate in the disease process of neurodevelopmental disorders, thus being potentially amenable to antibody-targeting interventional strategies in the future.

Prenatal HLA genotyping of uncultured amniotic fluid samples contaminated with maternal blood.

OBJECTIVE: Allogenic transplantation of umbilical cord blood (UCB) from HLA-identical siblings is a therapeutic concept of increasing importance. Prenatal HLA typing results can provide important information as to whether the UCB should be collected. Therefore, we tested the suitability of two methods based on polymerase chain reaction (PCR) for low-resolution HLA genotyping of uncultured amniocytes contaminated with maternal blood. STUDY DESIGN: Amniotic fluid samples (~10 mL, n = 4) were collected and divided into 5 equal sized portions. Subsequently, maternal blood was added to produce a series of varying degrees of artificial contamination ranging from 0% to 5% (vol/vol). Corresponding maternal blood and cord blood samples were collected and served as reference material. After DNA preparation, all samples were subjected to both PCR-SSP (sequence-specific primers) and PCR-SSO (sequence-specific oligonucleotides) typing procedures, designed for low-resolution typing of the highly polymorphic HLA-B locus. RESULTS: Both PCR tests were able to accurately predict the fetal HLA-B type when pure amniotic fluid was used in all cases. The PCR-SSP method could still determine the fetal HLA type at 0.1% contamination but not at levels above this; in contrast, PCR-SSO failed if any degree of contamination was present. CONCLUSION: Fetal cells from amniotic fluid represent a reasonable source for prenatal testing of the fetal HLA genotype with either the PCR-SSP or the PCR-SSO method. Low levels of contamination with maternal blood in the amniotic fluid are tolerated by the more robust PCR-SSP method. In contrast, the PCR-SSO procedure is more sensitive to any degree of contamination, but it is the method of choice if the amount of DNA is limited because of the very low volume of specimens of amniotic fluid available.