Arrhythmias Presenting in Neonatal Lupus

Abstract

Arrhythmogenicity and electrophysiological effects of anti-Ro ⁄ SSA antibodiesBased on the facts that there is no convincing evidence that maternal antibodies can cross the sarcolemma of a normal cardiac myocyte, essentially two major categories of mechanisms for congenital complete heart block (CHB) can be identified. The first is abnormal surface expression of intracellular SSA ⁄ Ro and SSB ⁄ La antigens, eventually induced by apoptosis [1, 2], viral infection [3], UV light and IFNc treatment [4]. The other mechanism is the cross-reactivity of maternal antibodies with targets other than SSA ⁄ Ro and SSB ⁄ La antigens. Maternal antibodies were reported to cross-react with laminin and with human cardiac myosin heavy chain at a critical stage during foetal cardiac development [5,6], but the L-type calcium channels seem particularly important in this hypothesis [7][8][9][10].After preliminary reports, [11,12] Boutjdir in an outstanding paper [7] showed that IgG-enriched fractions and anti-52-kD SSA ⁄ Ro antibodies affinity-purified from the sera of mothers whose children have CHB reversibly induce complete atrioventricular (AV) block in the human foetal heart perfused by the Langendorff technique. At 33 min of perfusion, complete AV block was observed with the presence of only P waves and missing QRS complexes. Reperfusion of the heart with antibodyfree Tyrode's solution for 48 min resulted in partial and slow recovery. Superfusion of hearts with IgG fractions from mothers with affected children also induced bradycardia and AV dissociation. In contrast, IgG from control mothers did not have any measurable effect on AV conduction. In the same paper, the authors showed that anti-Ro ⁄ SSA antibodies inhibit L-type Ca 2+ currents at the whole-cell and single-channel level. Immunization of female BALB ⁄ c mice with recombinant 52-kD SSA ⁄ Ro protein generated high-titre antibodies that crossed the placenta during pregnancy and were associated with varying degrees of AV conduction abnormalities, including complete AV block, in the pups. These findings suggest that anti-52-kD SSA ⁄ Ro antibodies are causally related to the development of CHB.The same group reported that the passive transfer of human anti-Ro/SSA into pregnant mice induced AbstractPerfusion of human foetal heart with anti-Ro ⁄ SSA antibodies induces transient heart block. Anti-Ro ⁄ SSA antibodies may cross-react with T-and L-type calcium channels, and anti-p200 antibodies may cause calcium to accumulate in rat heart cells. These actions may explain a direct electrophysiological effect of these antibodies. Congenital complete heart block is the more severe manifestation of so-called ''Neonatal Lupus''. In clinical practice, it is important to distinguish in utero complete versus incomplete atrioventricular (AV) block, as complete AV block to date is irreversible, while incomplete AV block has been shown to be potentially reversible after fluorinated steroid therapy. Another issue is the definition of congenital AV block, as cardiologists have considered co...

A Population‐based Investigation of the Autoantibody Profile in Mothers of Children with Atrioventricular Block

“…These women are commonly diagnosed with systemic lupus erythematosus (SLE) or Sjögren’s syndrome, but may also be asymptomatic. The fetal atrioventricular (AV) block usually develops during the 18th to 24th week of gestation after transfer of the maternal antibodies across the placenta, but can also be diagnosed later [3–5]. Following reports of increased incidence of sudden deaths in asymptomatic patients with AV block [6], a pacemaker is now commonly implanted at an early age.…”

Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern

“…However, association with the presence of maternal autoantibodies to Ro/SSA and/or La/SSB is well established,1 2 and the risk of complete congenital heart block is 1–2% in Ro/SSA-positive pregnancies 3–6. Furthermore, the reported risk of giving birth to a second child with complete heart block for anti-Ro/SSA-positive mothers ranges from 12% to 20%,7–9 despite the persistence of maternal autoantibodies 10.…”

Anti-Ro52 monoclonal antibodies specific for amino acid 200–239, but not other Ro52 epitopes, induce congenital heart block in a rat model

“…Congenital heart block (CHB) is a cardiac manifestation of the neonatal lupus syndrome, which may develop in fetuses of women with anti-Ro/SSA antibodies 1. During pregnancy, the maternal autoantibodies are transferred to the child and may initiate a series of events that will lead to cardiac inflammation, fibrosis and calcification, eventually blocking signal conduction at the atrioventricular (AV) node 2 3.…”