Dynamics of immunoglobulins at the feto-maternal interface

Saji, Fumitaka; Samejima, Yoshihiro; Kamiura, Shoji; Koyama, Masayasu

doi:10.1530/ror.0.0040081

Cited by 224 publications

(137 citation statements)

References 14 publications

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“…Exposure in late pregnancy and the resulting potential risk of postnatal infections 17 are associated with active placental drug transfer from mother to infant, mediated by binding of the Fc region to the neonatal Fc receptor (FcRn) 42. In contrast to other anti‐TNF agents, the CZP molecule lacks the Fc moiety, preventing binding to placental FcRn, thus limiting placental transport 43.…”

Section: Discussionmentioning

confidence: 99%

Pregnancy Outcomes After Exposure to Certolizumab Pegol

Clowse

Scheuerle

Chambers

et al. 2018

Arthritis & Rheumatology

142

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ObjectiveAnti–tumor necrosis factor (anti‐TNF) medications are effective in controlling chronic inflammatory diseases, but information about their use and safety in pregnancy is limited. Consequently, anti‐TNF agents are often discontinued early in gestation. Certolizumab pegol (CZP), a PEGylated, Fc‐free anti‐TNF agent approved for the treatment of rheumatic diseases and/or Crohn's disease, has minimal to no active placental transfer. This analysis was undertaken to evaluate pregnancy outcomes in women receiving CZP, especially those exposed during early pregnancy.MethodsProspective and retrospective data on maternal CZP exposure were extracted from the UCB Pharma safety database through March 6, 2017. Analysis was limited to prospective reports to avoid potential bias associated with retrospective submissions. The numbers of live births, miscarriages, elective abortions, stillbirths, and major congenital malformations were ascertained.ResultsOf 1,137 prospectively reported pregnancies with maternal exposure to CZP, 528 (including 10 twin pregnancies) had 538 known outcomes: 459 live births (85.3%), 47 miscarriages (8.7%), 27 elective abortions (5.0%), and 5 stillbirths (0.9%). There were 8 major congenital malformations (1.7%) among the 459 infants. First trimester exposure occurred in 367 (81.2%) of 452 pregnancies resulting in 459 live births. Exposure during all 3 trimesters occurred in 201 (44.5%) of 452 pregnancies.ConclusionThis analysis represents the largest cohort of pregnant women exposed to an anti‐TNF agent for management of chronic inflammatory diseases. Analysis of pregnancy outcomes does not indicate a teratogenic effect of CZP, compared to the general population, nor an increased risk of fetal death. The data are reassuring for women of childbearing age considering treatment with CZP.

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Section: Discussionmentioning

confidence: 99%

Pregnancy Outcomes After Exposure to Certolizumab Pegol

Clowse

Scheuerle

Chambers

et al. 2018

Arthritis & Rheumatology

142

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“…21 In addition, the four IgG subclasses are actively transported across syncytiotrophoblast and the villous fetal endothelial cells, and hence they reach the conceptus blood and protect him/her even for several months after birth. 82 Besides, Igs are produced by the human fetus by week 14 of gestation and they may be stimulated by antigens. 83,84 Four systems have been described for the constant heavy and k light chain genes of Igs, Gm, Am, Em and Km, with 24 allotypes.…”

Section: Igs and Fcrs Polymorphismsmentioning

confidence: 99%

“…Both FcgRIIIa and FcgRIIIb bind IgGl and IgG3 complexes, but not IgG2 or IgG4. 82,94 Transplacental transport of maternal IgG has classically been considered protective for the newborn against infection, and most of the IgG is transferred during the third trimester (Figure 1). 82 Thus, it would be reasonable that vertical transmission was lower by the end of gestation.…”

Section: Igs and Fcrs Polymorphismsmentioning

confidence: 99%

“…2 The FcRn is present in the syncytiotrophoblast and fetal endothelial cells, and binds IgG of the four subclasses with high affinity. 82,94 It mediates IgG transcytosis and immune complexes during pregnancy. 82,88,95 A variable number of tandem repeats (VNTR) region within the promoter, with five different alleles (VNTR1-VNTR5), has been studied in monocytes; this polymorphism influences FcRn expression leading to variable cellular IgG-binding activity.…”

Section: Igs and Fcrs Polymorphismsmentioning

confidence: 99%

“…82,94 It mediates IgG transcytosis and immune complexes during pregnancy. 82,88,95 A variable number of tandem repeats (VNTR) region within the promoter, with five different alleles (VNTR1-VNTR5), has been studied in monocytes; this polymorphism influences FcRn expression leading to variable cellular IgG-binding activity. VNTR3 homozygous monocytes express 1.66-fold more FcRn transcript than VNTR2/ VNTR3 heterozygous cells, and hence the latter show diminished IgG binding.…”

Section: Igs and Fcrs Polymorphismsmentioning

confidence: 99%

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PhysiologicIgGBiodistribution, Transport, and Clearance: Implications for Monoclonal Antibody Products

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Price‐Schiavi

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Pharmaceutical Sciences Encyclopedia

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Following administration, monoclonal antibodies become part of the endogenous IgG pool for distribution, transport, and clearance unless these physiologic processes are altered by antibody CDR‐epitope interactions. This article aims to provide helpful information regarding potential monoclonal antibody IgG test article (non‐CDR‐mediated) binding to specific tissues, cell types or other tissue elements, and subcellular locations following exogenous intravenous administration in animal model test systems.

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Dynamics of immunoglobulins at the feto-maternal interface

Cited by 224 publications

References 14 publications

Pregnancy Outcomes After Exposure to Certolizumab Pegol

Pregnancy Outcomes After Exposure to Certolizumab Pegol

Congenital toxoplasmosis: candidate host immune genes relevant for vertical transmission and pathogenesis

PhysiologicIgGBiodistribution, Transport, and Clearance: Implications for Monoclonal Antibody Products

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