Background The mechanism(s) responsible for the acquisition of maternal antibody isotypes other than IgG are not fully understood. offspring. In separate experiments FcRn+/? or FcRn?/? neonatal mice were gavage fed TNP-specific IgE as IgG1 anti-IgE/IgE immune complexes IgG1 isotype control and IgE or IgE alone. Mice were sacrificed 2 hours after feeding to determine serum levels and biologic activity of absorbed TNP-specific IgE. Results As expected the absorption Roburic acid of maternal OVA-specific IgG1 in FcRn?/? offspring was at levels 103-104 less than observed in FcRn+/+ or FcRn+/? offspring. Surprisingly FcRn expression also influenced the absorption of maternal IgE. OVA-specific IgE was detected in FcRn+/+ and FcRn+/? offspring but not in FcRn?/? offspring. IgG1 anti-IgE/IgE immune complexes were detected in allergic foster mothers and correlated strongly with levels in FcRn+/+ and FcRn+/? offspring (rho=0.88 P <0.0001). Furthermore FcRn expression was required for neonatal mice to absorb TNP-specific IgE when fed as IgG1 anti-IgE/IgE immune complexes. When immune complexes were generated with IgG1 anti-IgE directed against the Cε4 domain the absorbed IgE was able to function in antigen-dependent basophil degranulation. Conclusions and Clinical Relevance These data demonstrate a novel mechanism by which FcRn may facilitate absorption of maternal antibodies other than IgG. These findings are clinically relevant because FcRn mediates the transplacental passage of maternal IgG to the fetus. This raises the possibility that FcRn could mediate the transplacental passage of maternal IgE as IgG anti-IgE/IgE immune complexes. placental perfusion model Szepfalusi et al. demonstrated the placental transport of inhalant and nutritive allergens is increased in the presence of human immunoglobulin [20]. In addition the transplacental passage of exogenous insulin from mother to fetus is associated with the presence of anti-insulin antibodies suggesting in this situation that insulin can cross the placental barrier as IgG-insulin immune complexes [21]. Despite the finding that all 5 classes of antibodies are variably present in the serum of newborns [22;23] the mechanism(s) responsible for acquisition of maternal antibody isotypes other than IgG are not fully understood. Using a murine model of ovalbumin (OVA)-induced allergic airway disease (AAD) we previously demonstrated that allergen-specific IgG1 and IgE are absorbed from the neonatal gastrointestinal tract into the systemic circulation of na?ve mice nursed by Roburic acid allergic mothers [24;25]. In this report we demonstrate the absorption of allergen-specific IgE by breastfed offspring was dependent on offspring FcRn expression. Because it is generally thought that FcRn does not bind IgE [7;26] we hypothesized that IgE could be absorbed from the milk of allergic mothers as IgG anti-IgE/IgE immune complexes. To investigate this possibility we demonstrated that IgG1 anti-IgE/IgE immune complexes were present in the serum of allergic mothers and correlated strongly with the serum concentration of IgG1 anti-IgE/IgE immune complexes in breastfed offspring. Furthermore in neonatal mice fed IgG1 anti-IgE/IgE immune complexes the ability to absorb IgE into the systemic circulation was dependent on THEM4 FcRn. Our results suggest a mechanism by which FcRn may facilitate the absorption of maternal antibodies other than IgG. METHODS Animals C57BL/6J-wildtype or -FcRn-deficient (FcRn?/?) mice were obtained from Jackson Laboratories (Bar Harbor ME) or bred in our colony at the University of CT Health Center. All Roburic acid mice were fed sterile food and water and housed in microisolators under pathogen-free conditions. Their care was in accordance with institutional and Office of Laboratory Animal Welfare guidelines. To distinguish FcRn+/+ FcRn+/? and FcRn?/? mice genomic DNA was isolated from tail pieces Roburic acid and PCR was performed as described [27]. Generation of allergic foster mothers Maternal AAD was generated in 5-6 week old female C57BL/6J wildtype mice with two weekly immunizations by intraperitoneal (i.p.) injection of 8 μg or 0.32 μg/gram body weight OVA (grade V Sigma Chemical Co. St. Louis MO) adsorbed to Roburic acid 2 mg or 0.08 mg/gram body Roburic acid weight Al(OH)3. Seven to.