Maternal Antibodies against Fetal Cardiac Antigens in Congenital Complete Heart Block

Abstract

An immunologic basis for congenital heart block has been proposed previously. To investigate the association between congenital heart block and maternal antibodies capable of crossing the placenta, we used immunofluorescence to examine serum samples from 41 mothers and 8 affected children, together with serum from controls, for antibodies to fetal cardiac tissue. Twenty-one mothers (51 percent) had IgG antibody reactive with fetal heart tissue, as compared with only 9 of 94 controls (10 percent; P less than 0.001). Three of 8 affected babies, but none of 50 healthy babies, had similar antibodies. The antibodies reacted with all myocardial tissue and were not directed specifically to the conduction system. They also reacted with other fetal tissues and could be distinguished from nuclear and smooth-muscle autoantibodies. We also observed a higher occurrence of antibodies to cytomegalovirus, but not to Epstein-Barr virus, in these mothers. Autopsy specimens from babies with congenital heart block examined by immunoperoxidase staining showed deposition of immunoglobulin and complement components in all cardiac tissues. These findings strengthen the case implicating immune reactivity related to maternal antibody in the development of some but not all cases of congenital heart block.

Identification of mothers at risk for congenital heart block and other neonatal lupus syndromes in their children. comparison of enzyme‐linked immunosorbent assay and immunoblot for measurement of anti–ss‐a/ro and anti–ss‐b/la antibodies

“…Antibodies to SS-A/Ro and SS-B/La ribonucleoproteins in maternal sera have been almost universally demonstrable when neonatal lupus is identified in a child (4)(5)(6). These autoantibodies are found with high frequency in the sera of individuals with Sjogren's syndrome (SS) or systemic lupus erythematosus (SLE), in some of their clinically normal relatives, and occasionally in otherwise healthy individuals (7,8).…”

Complete congenital heart block is associated with increased autoantibody titers against calreticulin

“…It has been suggested that CCHB is a model of passively acquired autoimmune injury as a consequence of pathogenic maternal autoantibodies [4]. The reactivity between anti-Ro/SS-A antibodies and fetal cardiac tissue including the conduction system have been shown [5,6], as well as the presence of 52 kD and 60 kD Ro/SS-A and La/SS-B antigen in fetal heart tissue [7]. Alexander et al [8] have reported the inhibition of cardiac repolarization by anti-Ro/SS-A in vivo.…”

Anti-La (SS-B) but not anti-Ro52 (SS-A) antibodies cross-react with laminin—a role in the pathogenesis of congenital heart block?

“…Congenital heart block {CHB), a potentially fatal and irreversible disease of infants, has been suggested as a consequence of transplacental passage of maternal autoantibodies to the small ribonucleoproteins La/SS-B and Ro/SS-A (1)(2)(3). La (48 kD) is thought to be either a nuclear transcription termination factor (4], and/or a cytoplasmic protein capable of ATPdependent melting of RNA/DNA hybrids [5], Ro (52 or 60 kD) is a cytoplasmic antigen, whose precise biological function is unknown, Autoantibodies to Ro and La are found in autoimmune diseases such as primary Sjogren's syndrome (SS) or secondary Sjogren's syndrome accompanied by systemic lupus erythematosus (SLE) [6,7].…”