Faculty Bibliography

Neonatal lupus, albeit rare, affords an excellent opportunity to examine a disease from bedside to bench. Over the past year there have been numerous publications covering clinical aspects and basic research. The timing of heart block is not random; bradycardia is most often identified between 16 and 24 weeks of gestation. Investigations have focused on this apparently vulnerable period and examined the expression of known (SSA/Ro-SSB/La), novel (p57, endogenous retrovirus-3), and cross-reactive (laminin) autoantigens in fetal hearts of varied ages and in adult hearts. Clinical studies are accumulating, but a unique maternal autoantibody profile is yet to be identified. Anti-52-kD responses, measured by enzyme-linked immunosorbent assay and immunoblot, continue to be a nearly universal finding in mothers whose children have neonatal lupus. The presence of anti-U1RNP in the absence of anti-SSA/Ro-SSB/La antibodies occurs only in cases of isolated cutaneous disease and not (to date) in mothers of infants with cardiac manifestations. Immunogenetically, mothers with affected children appear to be more closely related to Sjogren's syndrome than systemic lupus erythematosus. Asymptomatic mothers do not invariably become ill, and if an asymptomatic mother does develop lupus it is not likely to be life threatening. Heart block is associated with substantial morbidity and mortality. Although treatment of affected fetuses with dexamethasone has successfully diminished associated effusions, this therapy has not reversed established third-degree block. Treatment with sympathomimetics may be beneficial in fetuses with hydropic changes. Prophylactic therapies, other than serial echocardiographic evaluation, are not supported by any published data. To further efforts at both the bench and bedside, research registries were recently established in the United States and Canada

Neonatal lupus is strongly associated with antibodies reactive with SSA/Ro-SSB/La proteins, independent of maternal disease activity or classification. We sought to determine whether the fine specificity of antibody profiles remains stable or evolves over time and whether these findings relate to clinical status. Sera from 23 mothers whose children had neonatal lupus (22 heart block, one skin) were evaluated by SDS-immunoblot. For each mother two samples were available at least 13 months apart; the mean duration of time between testing was 45 months +/- 27 S.D. (range 13-108 months). Twenty-two of the 23 initial profiles were identical to the results obtained in a later sample. The health status of seven (30%) of 23 mothers changed after the birth of the affected infant but the immunoblot specificity of the antibodies remained unchanged. SLE was the initial and final diagnosis in the only mother whose profiles differed, with development of weak reactivity to 48 kD SSB/La in addition to the 52kD SSA/Ro after 14 months. In conclusion, the fine specificity of anti-SSA/Ro-SSB/La antibodies as assessed by immunoblot is highly stable for years. Progression of clinical status was not associated with a concomitant change in antibody profile

OBJECTIVE. To compare the subclass distribution of anti-48 kDa La(SSB) and anti-52 and 60 kDa Ro(SSA) antibodies in the maternal and neonatal circulation, in pregnancies affected and unaffected by the development of congenital heart block (CHB). METHODS. Sera were obtained from 32 mothers (during 34 pregnancies 23 complicated by CHB and 11 healthy) demonstrated to have anti-Ro(SSA) and/or La(SSB). Maternal and neonatal autoantibodies were evaluated for subclass distribution by ELISA. RESULTS. All 4 subclasses of anti-Ro(SSA) and La(SSB) antibodies cross the placenta and are detectable in sera obtained from the umbilical cord, IgG1 and IgG3 were the major subclasses represented in the 48 kDa La(SSB) and 52 kDa Ro(SSA) responses. All subclasses, including IgG2 and IgG4, were observed in about one-third of the anti-52 kDa Ro(SSA) and 48 kDa La(SSB) responses. In contrast, anti-60 kDa antibodies were, with rare exception, confined to IgG1. Except for anti-48 kDa La(SSB) IgG3 antibodies, no significant differences were observed between affected and unaffected pregnancies in the ratio of maternal to neonatal levels of any of the antibody subclasses. Overall, there were no significant differences in the subclass profiles between mothers whose children had heart block and those who did not. CONCLUSION. The IgG subclasses of anti-48 kDa La(SSB) and anti-52 and 60 kDa Ro(SSA) do not account for the susceptibility of one fetus versus another for the development of CHB. Anti-60 kDa Ro(SSA) antibodies are more restricted in subclass distribution than anti-52 kDA Ro(SSA) or 48 kDa La(SSB) responses