Autoantibody response to the Ro/La particle may predict outcome in neonatal lupus erythematosus

Abstract

SUMMARYThis study was undertaken to determine the role of antibodies against both recombinant Ro (r-Ro) and La (r-La) proteins and polypeptides derived from the recombinant La protein in predicting fetal and neonatal outcome in children at risk to develop neonatal lupus erythematosus (NLE). All sera were obtained in the perinatal period and quantitative ELISA assays were used. We collected 41 maternal sera within 2 months of delivery ofa child with NLE (21 with congenital heart disease block (CHB) and 20 with dermalologic NLE) and 19 sera from anti-Ro and/or anti-La antibodypositive mothers with systemic lupus erythematosus (SLE) who delivered a child without NLE. All sera were tested for anti-r-La aod anti-r-Ro antibodies by ELISA, and most sera were tested for antibodies directed against La polypeptides by immunoblot. We found significantly higher anti-rLa antibody levels in the sera from mothers of children with NLE compared with sera from mothers of unaffected children (067 i 0-43 versus 0-14 ± 0-30: P < 0 0001). There was a statistically significant difference in the mean anti-r-La levels between the sera of mothers of children with CHB compared with dermatologic NLE (0-51 ±0 45 versus 083 ±0 37 respectively; /'^O 0091). When we examined antibodies directed against the recombinant 52-kD Ro protein, there was a statistically significant elevation of titres in the sera of mothers of NLE children (0 77±0 35) compared with non-NLE mothers (0'29±0 39; /*<OOOOI). There was no difference in the r-Ro levels between mothers of children with dermatologic NLE compared with CHB (0-82 ±0-37 versus 0 71 ±0 74; /'^O 32). When we examined polypeptides derived from the recombinant La protein, the mean number of polypeptides recognized by sera from mothers of children with NLE was significantly higher than the mean number of polypeptides recognized by sera from mothers of unaffected children (51 ±0-54 versus 2 3 ±0-54 respectively; /*<OOOI). More importantly, when we examined the individual polypeptides. we found that only sera from mothers of children with NLE and not from mothers of unaffected children recognized a polypeptide designated DD (30% versus 0%, respectively). These studies indicate that the autoantibody response to the Ro/La particle can differentiate sera from mothers of children with NLE and sera from mothers of unaffected children. Furthermore, there was a difference In the anti-La autoantibody response between mothers of children with CHB and dermatologic NLE. Antibodies directed against the DD polypeptide derived from the recombinant La protein were seen only in the sera of mothers of children with NLE.

The Importance of the Level of Maternal Anti-Ro/SSA Antibodies as a Prognostic Marker of the Development of Cardiac Neonatal Lupus Erythematosus

“…Previous studies have shown that all cases of cardiac NLE are associated with antibodies to at least 1 of the 52-and 60-kD Ro-particles and/or to the 48-kD La-protein (8,9). More recently, the response to peptides within the Ro-and La-proteins has also been examined (9,25,26).…”

“…It took another 20 years before this association became well recognized (3)(4)(5) and until the early 1980s that studies documented a close association between maternal anti-Ro/SSA and anti-La/SSB antibodies and congenital heart block (6,7). It was subsequently shown that the highest relative risks of CAVB were seen in offspring of mothers with antibodies against 52-kD Ro and 48-kD La proteins (8,9).…”

Neonatal Lupus Erythematosus

“…In addition to the traditional Ro antigen of 60kD, another antigen of 52kD has been identified. Antibodies with specificity for the 52 kD component of the SSA/Ro protein (Ro52) are more frequently found and are present at higher concentrations in the serum of children with congenital heart block and their mothers [14,15]. More specifically, maternal anti Ro-52 kD antibodies with primary specificity for a particular peptide fragment (amino acids 200 through 239, p200-239) are significantly associated with the development of CHB [15,16].…”

Neonatal Lupus Erythematosus (NLE)

“…In addition to inducing tissue damage, anti-SSA/Ro and/or anti-SSB/La antibodies inhibit calcium channel activation or the cardiac L-and T-type calcium channels themselves. L-type channels are crucial to action potential propagation and conduction in the AV node [Xiao GQ, 2001;Silverman, 1995]. Very few neonates who have maternal antibodies develop neonatal lupus.…”

“…Post mortem studies in the neonates revealed deposition of IgG1 & IgG3 along with complement (including C1q, C4, C3d, C6, and C9), and fibrin [6. Silverman, 1995;Salomonsson 2002] leading initially to pancarditis and later on to fibroelastosis of the heart. Thus it can involve almost all the structures of the heart.…”