Benefits and Risks of IgG Transplacental Transfer

Maternal passage of immunoglobulin G (IgG) is an important passive mechanism for protecting the infant while the neonatal immune system is still immature and ineffective. IgG is the only antibody class capable of crossing the histological layers of the placenta by attaching to the neonatal Fc receptor expressed at the level of syncytiotrophoblasts, and it offers protection against neonatal infectious pathogens. In pregnant women with autoimmune or alloimmune disorders, or in those requiring certain types of biological therapy, transplacental passage of abnormal antibodies may cause fetal or neonatal harm. In this review, we will discuss the physiological mechanisms and benefits of transplacental transfer of maternal antibodies as well as pathological maternal situations where this system is hijacked, potentially leading to adverse neonatal outcomes.

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Animal model of fetal and neonatal immune thrombocytopenia: role of neonatal Fc receptor in the pathogenesis and therapy

Blood ◽

10.1182/blood-2010-05-284919 ◽

2010 ◽

Vol 116 (18) ◽

pp. 3660-3668 ◽

Cited By ~ 61

Author(s):

Pingguo Chen ◽

Conglei Li ◽

Sean Lang ◽

Guangheng Zhu ◽

Adili Reheman ◽

...

Keyword(s):

Animal Model ◽

Immunoglobulin G ◽

Immune Thrombocytopenia ◽

Fc Receptor ◽

Maternal Antibodies ◽

Severe Bleeding ◽

Neonatal Fc Receptor ◽

Igg Isotypes ◽

Β3 Integrin

Abstract Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder in which maternal antibodies cross the placenta and destroy fetal/neonatal platelets. It has been demonstrated that the neonatal Fc receptor (FcRn) regulates immunoglobulin G (IgG) homeostasis and plays an important role in transplacental IgG transport. However, the role of FcRn in the pathogenesis and therapy of FNIT has not been studied. Here, we developed an animal model of FNIT using combined β3 integrin–deficient and FcRn-deficient (β3−/−FcRn−/−) mice. We found that β3−/−FcRn−/− mice are immunoresponsive to β3+/+FcRn−/− platelets. The generated antibodies were β3 integrin specific and were maintained at levels that efficiently induced thrombocytopenia in adult β3+/+FcRn−/− mice. FNIT was observed when immunized β3−/−FcRn+/+ females were bred with β3+/+FcRn+/+ males, while no FNIT occurred in β3−/−FcRn−/− females bred with β3+/+FcRn−/− males, suggesting that FcRn is indispensable for the induction of FNIT. We further demonstrated that fetal FcRn was responsible for the transplacental transport of various IgG isotypes. We found that anti-FcRn antibody and intravenous IgG prevented FNIT, and that intravenous IgG ameliorated FNIT through both FcRn-dependent and -independent pathways. Our data suggest that targeting FcRn may be a potential therapy for human FNIT as well as other maternal pathogenic antibody-mediated diseases.

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PROTECTION AGAINST Rh SENSITIZATION AND PREVENTION OF ERYTHROBLASTOSIS FETALIS

PEDIATRICS ◽

10.1542/peds.41.1.1 ◽

1968 ◽

Vol 41 (1) ◽

pp. 1-4

Author(s):

Louis K. Diamond

Keyword(s):

Blood Group ◽

Hemolytic Anemia ◽

Fetal Death ◽

Maternal Antibodies ◽

Group Factor ◽

Transplacental Passage ◽

Fetal Hydrops ◽

Good Fortune ◽

Sequence Of Events ◽

Blood Group Factor

Rarely has it been our good fortune to have a disease recognized, its cause clearly determined, its treatment successfully developed to a great extent, and then its prevention found, all in one generation. It is gratifying to be able to review such a sequence of events, especially the latest advance. In 1932, we1 drew together and defined as a single entity, generally called erythroblastosis fetalis, four conditions previously described separately, namely late fetal death with erythroblastosis in the tissues, fetal hydrops, congenital anemia of the newborn, and icterus gravis neonatorum.In 1941, Philip Levine and coworkers2 astutely surmised that the disease resulted from immunization of the mother against a blood group factor of her infant and the development of hemolytic anemia in the baby from the transplacental passage of maternal antibodies.

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Maternal antibody persistence: a neglected life-history trait with implications from albatross conservation to comparative immunology

Proceedings of The Royal Society B Biological Sciences ◽

10.1098/rspb.2011.2277 ◽

2011 ◽

Vol 279 (1735) ◽

pp. 2033-2041 ◽

Cited By ~ 48

Author(s):

R. Garnier ◽

R. Ramos ◽

V. Staszewski ◽

T. Militão ◽

E. Lobato ◽

...

Keyword(s):

Life History ◽

Growth Period ◽

Maternal Antibodies ◽

Life History Strategies ◽

Life History Trait ◽

Comparative Immunology ◽

Physiological Mechanisms ◽

Antibody Persistence ◽

Temporal Persistence ◽

Potential Impact

The evolution of different life-history strategies has been suggested as a major force constraining physiological mechanisms such as immunity. In some long-lived oviparous species, a prolonged persistence of maternal antibodies in offspring could thus be expected in order to protect them over their long growth period. Here, using an intergenerational vaccination design, we show that specific maternal antibodies can display an estimated half-life of 25 days post-hatching in the nestlings of a long-lived bird. This temporal persistence is much longer than previously known for birds and it suggests specific properties in the regulation of IgY immunoglobulin catabolism in such a species. We also show that maternal antibodies in the considered procellariiform species are functional as late as 20 days of age. Using a modelling approach, we highlight that the potential impact of such effects on population viability could be important, notably when using vaccination for conservation. These results have broad implications, from comparative immunology to evolutionary eco-epidemiology and conservation biology.

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Maternal Antibodies Enhance or Prevent Cytomegalovirus Infection in the Placenta by Neonatal Fc Receptor-Mediated Transcytosis

American Journal Of Pathology ◽

10.2353/ajpath.2006.050482 ◽

2006 ◽

Vol 168 (4) ◽

pp. 1210-1226 ◽

Cited By ~ 149

Author(s):

Ekaterina Maidji ◽

Susan McDonagh ◽

Olga Genbacev ◽

Takako Tabata ◽

Lenore Pereira

Keyword(s):

Cytomegalovirus Infection ◽

Fc Receptor ◽

Maternal Antibodies ◽

Neonatal Fc Receptor

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The Metabolism and Transplacental Transfer of Oseltamivir in the Ex Vivo Human Model

Infectious Diseases in Obstetrics and Gynecology ◽

10.1155/2008/927574 ◽

2008 ◽

Vol 2008 ◽

pp. 1-5 ◽

Cited By ~ 29

Author(s):

Kevin C. Worley ◽

Scott W. Roberts ◽

Roger E. Bawdon

Keyword(s):

Active Metabolite ◽

Ex Vivo ◽

Reference Method ◽

Human Model ◽

Transplacental Passage ◽

Oseltamivir Carboxylate ◽

Ex Vivo Model ◽

Transplacental Transfer ◽

Perfusion Studies ◽

Oseltamivir Phosphate

Oseltamivir phosphate is extensively metabolized in the ex vivo human placenta model, and the transplacental passage of the metabolite oseltamivir carboxylate is incomplete.Objective. To evaluate the metabolism and transplacental transfer of oseltamivir (Tamiflu) in the ex vivo human placental model.Study Design. Perfusion studies were performed in six placentas from term, uncomplicated deliveries. Concentrations of oseltamivir phosphate (OP) that were 5-6 fold, 20–30 fold, and 600–800 fold above the therapeutic peak were tested, as neither OP nor its active metabolite, oseltamivir carboxylate (OC), could be detected at near-therapeutic concentrations. The transplacental transfer and accumulation of OC were assessed using the antipyrine reference method.Results. OP was extensively metabolized to OC. In the 4 placentas with the highest concentration of OP, OC had a mean clearance index of , suggesting that transplacental passage occurs at a relatively low rate. Measurable fetal accumulation occurred in the two placentas with the highest initial concentrations.Conclusions. Oseltamivir phosphate was extensively metabolized in the ex vivo model. Transplacental transfer of the metabolite was incomplete and accumulation was minimal.

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Human IgE does not bind to human FcRn

Scientific Reports ◽

10.1038/s41598-021-03852-1 ◽

2022 ◽

Vol 12 (1) ◽

Author(s):

Maximilian Brinkhaus ◽

Elvera J. van der Kooi ◽

Arthur E. H. Bentlage ◽

Pleuni Ooijevaar-de Heer ◽

Ninotska I. L. Derksen ◽

...

Keyword(s):

Surface Plasmon Resonance ◽

Immune Responses ◽

Surface Plasmon ◽

Plasmon Resonance ◽

Placental Transfer ◽

Direct Interaction ◽

Transplacental Passage ◽

Neonatal Fc Receptor ◽

Β2 Microglobulin ◽

Environmental Antigens

AbstractThe neonatal Fc receptor (FcRn) is known to mediate placental transfer of IgG from mother to unborn. IgE is widely known for triggering immune responses to environmental antigens. Recent evidence suggests FcRn-mediated transplacental passage of IgE during pregnancy. However, direct interaction of FcRn and IgE was not investigated. Here, we compared binding of human IgE and IgG variants to recombinant soluble human FcRn with β2-microglobulin (sFcRn) in surface plasmon resonance (SPR) at pH 7.4 and pH 6.0. No interaction was found between human IgE and human sFcRn. These results imply that FcRn can only transport IgE indirectly, and thereby possibly transfer allergenic sensitivity from mother to fetus.

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