Related Experiment Videos
Neonatal Guillain-Barré syndrome: blocking antibodies transmitted from mother to child
B Buchwald1, M de Baets, G J Luijckx
1Neurologische Klinik der Bayerischen, Julius-Maximilians-Universität, Würzburg, Germany.
Insights
Blocking antibodies transferred from mother to infant caused neonatal Guillain-Barré syndrome (GBS). These antibodies targeted mature neuromuscular junctions, explaining the delayed onset of GBS in the neonate.
Area of Science:
- Neurology
- Immunology
- Developmental Biology
Background:
- Neonatal Guillain-Barré syndrome (GBS) is rare but severe.
- Maternal GBS can pose risks to the neonate via transplacental antibody transfer.
Observation:
- A neonate born to a mother with active GBS developed the condition 12 days postpartum.
- Maternal and infant serum samples showed significant blockade of neuromuscular transmission.
Findings:
- Blocking antibodies, confirmed by immunoglobulin G (IgG) and Fab fragments, reduced quantal content by 90% and postsynaptic current amplitude by 30-40%.
- IgM antibodies to GM1 ganglioside were detected, but not IgG to common GBS targets.
- Blocking activity was absent in recovered mother and infant sera and in 5-day-old rats, but present in 23-day-old rats.
Implications:
- Transplacentally transferred blocking antibodies may target mature, but not fetal, neuromuscular junction epitopes.
- This antibody specificity could explain the delayed onset of neonatal GBS.
- Understanding these mechanisms is crucial for managing maternal and neonatal autoimmune neurological disorders.
Objective:
To investigate the role of blocking antibodies in neonatal Guillain-Barré syndrome (GBS) occurring 12 days postpartum in a child born to a mother with ongoing GBS.
Methods:
We studied plasma filtrate, purified IgG, and monovalent Fab fragments from the affected mother and serum from the neonate as well as serum samples after recovery from disease 3 months later. Experiments were performed on the hemidiaphragms of adult mice and neonatal and juvenile rats. Quantal endplate currents were recorded with the perfused macro-patch clamp electrode.
Results:
A dual effect was seen. Serum from mother and infant depressed quantal content by approximately 90% and reduced the amplitude of postsynaptic currents by 30 to 40%. The antibody nature of the blockade could be confirmed by showing that monovalent Fab fragments were similarly effective as purified immunoglobulin (Ig) G. No IgG antibodies to gangliosides, fetal or adult nicotinic acetylcholine receptor, or voltage-gated calcium channels could be detected, but IgM antibodies to the ganglioside GM1 were present. After recovery from GBS no blocking activity was seen in the sera of mother and infant. To elucidate why neonatal disease onset was delayed we examined the possible influence of early developmental changes in functional properties of the neuromuscular junction and applied the mother's active serum to postnatal rats. Although blockade was present in 23-day-old rats, it was absent in 5-day-old rats.
Conclusion:
Transplacentally transferred blocking antibodies may be specifically directed at epitopes of the mature but not the fetal neuromuscular junction.