Neonatal lupus syndrome: the heart as a target of the immune system

Abstract

Neonatal lupus erythematosus (NLE) is an auto-immune disease related to systemic lupus erythematosus (SLE). Unlike SLE it is not a spontaneous syndrome but rather an acquired one. In NLE the most common disease manifestations are a transient cutaneous lesion and cardiac conduction disturbances. The cutaneous lesions and other non-cardiac manifestations of NLE are transient and disappear about six months after birth, at the time when maternal antibodies disappear from the neonatal circulation. This fact suggests that maternal antibodies may cross the placenta leading to an inflamatory reaction in the fetal tissues. NLE is the principal cause of atria-ventricular block, when it is not associated with congenital birth defects. All the clinical studies to date correlate the heart block in NLE with the presence of certain types of circulating maternal antibodies, against the Ro/SSA nuclear proteins, in the serum of the newborn. In this paper we discuss animal models that have been developed by our and others groups to study the participation of the anti-Ro/SSA antibodies in the pathogenesis of the cardiac conduction blockades that occur in NLE.

Sera from patients with idiopathic dilated cardiomyopathy decrease ICa in cardiomyocytes isolated from rabbits

“…In that regard, Masuda et al (26) have shown that the muscarinic-like action of Chagasic antibodies could be blocked by the incubation of sera from the patients with peptides derived from the P2␤ family of T. cruzi ribosomal protein, carrying a stretch of negative charges at the carboxyl terminal end. In neonatal lupus, a well-known autoimmune syndrome that is associated with autoantibodies reactive to intracellular ribonucleoproteins (SSA/Ro and SSB/La), antibodies present in the mother's serum also have the ability to induce cardiac disturbances that are related to I Ca,L activity (12,33). However, in this case, direct interaction of the antibodies with the pore-forming subunit (␣-1C) of the L-type Ca 2ϩ channel occurs, leading to a strong inhibition (ϳ50%) of the current flowing through this channel (38).…”

Neonatal Lupus Erythematosus

“…The most common clinical manifestations of NLE are, in decreasing order of frequency, dermatologic, cardiac, and hepatic abnormalities [1, 5, 10, 16, 25]. Some infants may also have hematologic, neurologic, or splenic abnormalities [5, 7, 10, 16].…”

“…The cardiac manifestations include conduction abnormalities (first-, second-, and third-degree heart block) and cardiomyopathy [1, 2, 5, 24, 31]. Third-degree heart block, once established, is usually irreversible [26].…”

“…Neonatal lupus erythematosus (NLE) refers to a clinical spectrum of cutaneous, cardiac, and systemic abnormalities observed in newborn infants whose mothers have autoantibodies against Ro/SSA, La/SSB, and, less commonly, U1-ribonucleoprotein (U1-RNP) [1–3]. The condition was first described in 1954 by McCuistion and Schoch who reported a case of transient lupus skin lesion in an infant with an ANA-positive mother [4].…”

Anti‐La/SSB antibodies transported across the placenta bind apoptotic cells in fetal organs targeted in neonatal lupus

“…Congenital heart block (CHB) is the most severe manifestation of NLS and is characterized in postmortem studies by inflammation and connective tissue replacement of the fetal conduction system (6, 7). The role of anti‐Ro/La autoantibodies in the selective fetal tissue injury is poorly understood (5, 8–10).…”