The Fetal/Adult Acetylcholine Receptor Antibody Ratio in Mothers with Myasthenia Gravis as a Marker for Transfer of the Disease to the Newborn

Gardnerova, M.; Eymard, B.; Morel, E.; Faltin, M; Zajac, J; Sadovsky, Oliver; Tripon, P; Domergue, M.; Garabedian, Béatrice Vernet-der; Bach, Jae Hyung

doi:10.1212/wnl.48.1.50

Cited by 57 publications

(29 citation statements)

References 17 publications

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“…Third, the clinical manifestations of human neonatal autoimmune diseases are often not explicable by direct Ab action. In myasthenia gravis neonatal Abs were found to recognize epitopes unique to fetal acetylcholine receptors (53). In congenital heart block associated with maternal Ro52 autoantibodies, 50% of the mothers were free of clinical lupus, and none of them developed cardiac conduction defects.…”

Section: Discussionmentioning

confidence: 99%

Maternal Autoantibody Triggers De Novo T Cell-Mediated Neonatal Autoimmune Disease

Setiady¹,

Samy

Tung

2003

The Journal of Immunology

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Although human maternal autoantibodies may transfer transient manifestation of autoimmune disease to their progeny, some neonatal autoimmune diseases can progress, leading to the loss of tissue structure and function. In this study we document that murine maternal autoantibody transmitted to progeny can trigger de novo neonatal pathogenic autoreactive T cell response and T cell-mediated organ-specific autoimmune disease. Autoantibody to a zona pellucida 3 (ZP3) epitope was found to induce autoimmune ovarian disease (AOD) and premature ovarian failure in neonatal, but not adult, mice. Neonatal AOD did not occur in T cell-deficient pups, and the ovarian pathology was transferable by CD4+ T cells from diseased donors. Interestingly, neonatal AOD occurred only in pups exposed to ZP3 autoantibody from neonatal days 1–5, but not from day 7 or day 9. The disease susceptibility neonatal time window was not related to a propensity of neonatal ovaries to autoimmune inflammation, and it was not affected by infusion of functional adult CD4+CD25+ T cells. However, resistance to neonatal AOD in 9-day-old mice was abrogated by CD4+CD25+ T cell depletion. Finally, neonatal AOD was blocked by Ab to IgG-FcR, and interestingly, the disease was not elicited by autoantibody to a second, independent native ZP3 B cell epitope. Therefore, a new mechanism of neonatal autoimmunity is presented in which epitope-specific autoantibody stimulates de novo autoimmune pathogenic CD4+ T cell response.

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Section: Discussionmentioning

confidence: 99%

Maternal Autoantibody Triggers De Novo T Cell-Mediated Neonatal Autoimmune Disease

Setiady¹,

Samy

Tung

2003

The Journal of Immunology

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“…In der Literatur finden sich Hinweise darauf, dass die klinische Symptomatik des Neugeborenen mit der Höhe der Serumkonzentration der AChR-AK bei der Schwangeren korreliert [16,17,23,25,34,35]. Umgekehrt scheint das MyasthenieRisiko für Neugeborene von Müttern, die zum Zeitpunkt der Geburt in Remission sind, geringer zu sein [12,17,21,26,29,35,36].…”

Section: Eine Immungenetische Prädisposition Wird Diskutiertunclassified

“…Umgekehrt scheint das MyasthenieRisiko für Neugeborene von Müttern, die zum Zeitpunkt der Geburt in Remission sind, geringer zu sein [12,17,21,26,29,35,36]. Unklar ist bisher aber, warum nicht jedes Neugeborene einer Myasthenie-Patientin erkrankt bzw.…”

Section: Eine Immungenetische Prädisposition Wird Diskutiertunclassified

Transiente neonatale Myasthenia gravis

et al. 2002

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Ten to twenty percent of the offspring of mothers suffering from myasthenia gravis (MG) also develop transient neonatal MG, since maternal antibodies are able to cross the placenta. We report the course of two newborns of a mother with MG and a healthy father. The first pregnancy was complicated during the 3rd trimester by a hydramnion. The newborn presented with generalized muscle weakness, respiratory distress, weak sounding, anaemia, and poor sucking. Mechanical ventilation was necessary. Confirmation of the diagnosis was achieved by the result of repetitive muscle stimulation, showing a typical decrement in the EMG, and measurement of serum antiacetylcholin receptor antibodies. For 3 months, the infant was treated with neostigmin (cholinesterase inhibitor). After 26 days of hospitalization, the patient was released and followed up regularly. Myasthenic symptoms completely resolved. Side effects of the treatment were not observed. The course of the second pregnancy was normal. This second newborn was healthy. Our case report is remarkable for the very different presentation of two children of the same mother with MG during pregnancy and after delivery, with one child developing severe transient neonatal MG, initially requiring intensive care unit (ICU) treatment followed by quick recovery, and one child being healthy. We also present a score for monitoring the clinical course and adjusting anticholinesterase therapy accordingly.

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“…Neonatal myasthenia is seen in 10-20% and could be predicted by the fetal/adult acetylcholine receptor antibody ratio [5]. Severe symptoms at 12-48 h after delivery can be treated by cholinesterase inhibitors, but in most cases supportive treatment only is sufficient.…”

Section: Discussionmentioning

confidence: 99%