Journal of pediatric surgery · 2025
Prenatal administration of Immunoglobulin-M (IgM) via transamniotic fetal immunotherapy (TRAFIT).
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Huang Alex L, Scire Emily M, Dang Tanya T, Tai Melody, Bechara Beatriz S, Yohannes Blen, Kycia Ina, Zurakowski David, Fauza Dario O
Аннотация
PURPOSE: Immunoglobulin-M (IgM) is the first antibody class produced during an immune response, playing a crucial role in early defense mechanisms. Its large pentameric or hexameric structure, however, prevents it from crossing the placenta from mother to fetus during pregnancy. We sought to determine whether IgM is amenable to transamniotic fetal delivery utilizing a healthy rodent model.
METHODS: Fetuses (n = 42) from three time-dated pregnant dams received intra-amniotic injections on gestational day 17 (E17, term = E21-22) of either a solution of human IgM antibodies suspended in saline (n = 27) or just saline (n = 15), the latter to control for IgM interspecies homology. Samples from 9 fetal and annexial sites (umbilical cord, gestational membranes, placenta, and fetal spleen, thymus, intestine, liver, bone marrow, and serum) were procured at term for semi-quantitative fluorescence ELISA. Statistical comparisons were performed with and without nesting to account for individual mothers (p < 0.05).
RESULTS: Overall survival was 90.5 % (38/42) with no significant differences between the groups. In non-nested comparisons, significantly elevated relative fluorescence was detected in IgM exposed animals at all sites studied (p < 0.001 for spleen, thymus, umbilical cord, gestational membranes, placenta, thymus, liver, bone marrow, and serum and p = 0.001 for intestine). In nested comparisons, all sites also showed significantly elevated fluorescence in the IgM exposed group (p = 0.009 to <0.001) except for spleen (p = 0.064).
CONCLUSIONS: Fetal administration of immunoglobulin-M (IgM) is viable via the transamniotic route. Transamniotic fetal immunotherapy (TRAFIT) utilizing IgM may become a valuable minimally invasive option for prevention and/or treatment of select perinatal infections.
LEVEL OF EVIDENCE: N/A (animal and laboratory study).
TYPE OF STUDY: animal and laboratory study.
METHODS: Fetuses (n = 42) from three time-dated pregnant dams received intra-amniotic injections on gestational day 17 (E17, term = E21-22) of either a solution of human IgM antibodies suspended in saline (n = 27) or just saline (n = 15), the latter to control for IgM interspecies homology. Samples from 9 fetal and annexial sites (umbilical cord, gestational membranes, placenta, and fetal spleen, thymus, intestine, liver, bone marrow, and serum) were procured at term for semi-quantitative fluorescence ELISA. Statistical comparisons were performed with and without nesting to account for individual mothers (p < 0.05).
RESULTS: Overall survival was 90.5 % (38/42) with no significant differences between the groups. In non-nested comparisons, significantly elevated relative fluorescence was detected in IgM exposed animals at all sites studied (p < 0.001 for spleen, thymus, umbilical cord, gestational membranes, placenta, thymus, liver, bone marrow, and serum and p = 0.001 for intestine). In nested comparisons, all sites also showed significantly elevated fluorescence in the IgM exposed group (p = 0.009 to <0.001) except for spleen (p = 0.064).
CONCLUSIONS: Fetal administration of immunoglobulin-M (IgM) is viable via the transamniotic route. Transamniotic fetal immunotherapy (TRAFIT) utilizing IgM may become a valuable minimally invasive option for prevention and/or treatment of select perinatal infections.
LEVEL OF EVIDENCE: N/A (animal and laboratory study).
TYPE OF STUDY: animal and laboratory study.