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H 435‐containing immunoglobulin G 3 allotypes are transported efficiently across the human placenta: implications for alloantibody‐mediated diseases of the newborn
Author(s) -
Einarsdottir Helga,
Ji Yanli,
Visser Remco,
Mo Chunyan,
Luo Guangping,
Scherjon Sicco,
Schoot C. Ellen,
Vidarsson Gestur
Publication year - 2014
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.12334
Subject(s) - placenta , antibody , immunoglobulin g , immunology , biology , medicine , fetus , pregnancy , genetics
Background The neonatal receptor ( FcRn ) extends the half‐life of human immunoglobulin (Ig)G and transports it across the placenta, providing the newborn with humoral immunity. Of the four subclasses, IgG 3 stands out with strong effector functions, short half‐life (7 days vs. 21 days for other subclasses), and poor placental transport. We recently described how a single‐amino‐acid polymorphism at P osition 435 in IgG 3 is sufficient to explain the short half‐life of R 435‐containing IgG 3 and demonstrated that H 435‐ IgG 3 has a normal half‐life of 21 days. Here, we investigated whether the R 435 also explains the relatively poor placental transport of IgG 3. Study Design and Methods Sera were collected from paired mothers and newborns at birth. The study included six mothers expressing R 435‐ IgG diagnosed with fetal and neonatal alloimmune thrombocytopenia and treated with intravenous immune globulin ( IVIG ; containing H 435‐ IgG 3, also known as G 3m16 or G 3m(s,t) allotype), as well as 33 paired samples of both G 3m16 − and G 3m16 + mothers. Placental IgG transport was estimated by comparing cord and maternal concentrations of IgG subclass and G 3m16 allotype. Results The placental transport of naturally occurring H 435‐ IgG 3 allotypes was significantly more efficient than that of other R 435‐ IgG 3 allotypes and was comparable to IgG 1 transport. Conclusion We demonstrate that the poor maternal–fetal transport of IgG 3 is only true for most individuals of western populations where the G 3m16 is not common. In G 3m16 + individuals, expressing H 435‐containing IgG3 , IgG 3 transport is similar to IgG 1, which may give rise to enhanced complications in pregnancy‐associated alloimmune disease in ethnic communities where this naturally occurring H 435 containing IgG 3 allotype is more frequent.