Placental and fetal cardiac laminin are targets for cross-reacting autoantibodies from mothers of children with congenital heart block.
The association of congenital heart block (CHB) with maternal autoantibodies to the Ro and La ribonucleoprotein antigens may be due to cross-reactions between maternal anti-La antibodies and fetal cardiac specific antigens. One of the major components of cardiac myocytes, laminin, is accessible for binding by maternal autoantibodies and we have previously reported cross-reactivity of mouse laminin with anti-La antibodies affinity purified from the sera of patients with primary Sjögren's syndrome. Affinity purified anti-La antibodies from ten women who had at some time given birth to a child with CHB were examined for cross-reactivity with human placental laminin, which shares structural similarities with cardiac laminin. All ten anti-La antibodies bound to the surface of cryosections of normal full term placental trophoblasts. Binding could be inhibited by pre-incubation of antibodies with either La or placental laminin. Eight anti-La antibodies also reacted with placental laminin by ELISA and La inhibited up to 82% of binding to laminin while laminin inhibited up to 85% of binding to La in a dose dependent manner. Eight anti-La antibodies also bound to the surface of fetal cardiac myocytes at 10.3 weeks of gestation and five showed lower levels of reactivity with the surface of fetal cardiac myocytes at 16.5 weeks of gestation. None showed any surface staining of normal adult heart. These data confirm the cross-reactivity of anti-La antibodies with laminin and may support a placental role in preventing the majority of potentially pathogenic antibodies from reaching the fetal circulation.
Horsfall
A C
AC
Kennedy Institute of Rheumatology, London.
Li
J M
JM
Maini
R N
RN
D001323:Autoantibodies / Q000276:immunology / Q000378:metabolism; D001324:Autoantigens / Q000276:immunology; D015153:Blotting, Western; D003429:Cross Reactions; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005333:Fetus / Q000737:chemistry; D006321:Heart / Q000196:embryology; D006327:Heart Block / Q000151:congenital* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007797:Laminin / Q000276:immunology* / Q000378:metabolism; D008431:Maternal-Fetal Exchange / Q000276:immunology; D009206:Myocardium / Q000737:chemistry; D010920:Placenta / Q000737:chemistry; D011247:Pregnancy; D011485:Protein Binding / Q000502:physiology; D012261:Ribonucleoproteins / Q000276:immunology; D000097585:SS-B Antigen
D001323:Autoantibodies; D001324:Autoantigens; D007797:Laminin; D012261:Ribonucleoproteins; D000097585:SS-B Antigen