Maternal alloimmune IgG causes anti-glomerular basement membrane disease in perinatal transgenic mice that express human laminin α5
| Autor: | Manuel Patarroyo, Larysa Stroganova, Dorin-Bogdan Borza, Dale R. Abrahamson, Brooke M. Steenhard, Margaret G. Petroff, Patricia L. St. John, Adrian Zelenchuk |
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| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine Anti-Glomerular Basement Membrane Disease 030232 urology & nephrology Fc receptor Mice Transgenic 03 medical and health sciences 0302 clinical medicine Pregnancy Laminin Placenta Glomerular Basement Membrane medicine Animals Humans Basement membrane Fetus biology Glomerulonephritis medicine.disease Immunity Humoral 030104 developmental biology medicine.anatomical_structure Animals Newborn Transcytosis Nephrology Immunoglobulin G Immunology biology.protein Female |
| Zdroj: | Kidney International. 96:1320-1331 |
| ISSN: | 0085-2538 |
| Popis: | Mammalian immune systems are not mature until well after birth. However, transfer of maternal IgG to the fetus and newborn usually provides immunoprotection from infectious diseases. IgG transfer occurs before birth in humans across the placenta and continues after birth across the intestine in many mammalian species, including rodents. Transfer, which is mediated by the neonatal IgG Fc receptor, occurs by transcytosis across placental syncytiotrophoblasts and intestinal epithelium. Although maternal IgG is generally beneficial, harmful maternal allo- and autoantibodies can also be transferred to the fetus/infant, resulting in serious disease. To test this we generated transgenic mice that widely express human laminin α5 in their basement membranes. When huLAMA5 transgenic males were crossed with wild-type females, there was a maternal anti-human laminin α5 immune response. Maternal IgG alloantibody crossed the yolk sac and post-natal intestine in vivo and bound in bright, linear patterns to kidney glomerular basement membranes of transgenic fetuses/neonates but not those of wild-type siblings. By postnatal day 18, most transgenic mice were proteinuric, had glomerular C3 deposits and inflammatory cell infiltrates, thickened and split glomerular basement membranes, and podocyte foot process effacement. Thus, our novel model of perinatal anti-glomerular basement membrane disease may prove useful for studying pediatric glomerulopathies, formation of the fetomaternal interface, and maternal alloimmunization. |
| Databáze: | OpenAIRE |
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