Cross-reactive maternal autoantibodies and congenital heart block.
Epitopes with linear sequences recognized by anti-La autoantibodies from seven mothers of children with congenital heart block were recently defined. Eight of these epitopes share sequence identity with three other proteins in addition to the original autoantigen, La. The three proteins are human cardiac myosin beta heavy chain, laminin B1 chain and the M6 protein of Streptococcus pyogenes. Affinity purified anti-La antibodies from a further three mothers bound to the La antigen and also to human cardiac myosin and mouse laminin. Affinity purified antibodies from three mothers of healthy children bound to the La antigen but showed minimal binding to either human cardiac myosin or mouse laminin. Cardiac myosin inhibited the binding of CHB-related anti-La antibodies to both La and myosin. These data support a role for maternal autoantibodies crossing the placenta and recognizing foetal cardiac antigens accessible at a critical developmental stage during gestation. We suggest that this would lead to complement fixation, inflammation and the subsequent pathology associated with congenital heart block.
Horsfall
A C
AC
Kennedy Institute of Rheumatology, Bute Gardens, London, UK.
Rose
L M
LM
D000595:Amino Acid Sequence; D000915:Antibody Affinity; D000942:Antigens, Bacterial / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins / Q000276:immunology; D015153:Blotting, Western; D002352:Carrier Proteins; D003429:Cross Reactions; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000235:genetics; D005260:Female; D006327:Heart Block / Q000151:congenital / Q000209:etiology*; D006801:Humans; D007797:Laminin / Q000276:immunology; D008431:Maternal-Fetal Exchange; D008969:Molecular Sequence Data; D009218:Myosins / Q000276:immunology; D011247:Pregnancy; D012261:Ribonucleoproteins / Q000276:immunology; D017385:Sequence Homology; D012859:Sjogren's Syndrome / Q000276:immunology; D000097585:SS-B Antigen
D000942:Antigens, Bacterial; D001323:Autoantibodies; D001324:Autoantigens; D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D002352:Carrier Proteins; D000939:Epitopes; D007797:Laminin; D009218:Myosins; D012261:Ribonucleoproteins; D000097585:SS-B Antigen; C014689:streptococcal M protein