Antibodies to amino acid 200–239 (p200) of Ro52 as serological markers for the risk of developing congenital heart block

Abstract

SummaryMaternal autoantibodies to the p200-epitope of Ro52 have been suggested to correlate with development of congenital heart block. The aim of the present study was to evaluate the clinical relevance and predictive value of p200-antibodies in high-risk pregnancies. Sera from 515 Finnish, Swedish and American women were included in the study. Sera originated from 202 mothers with an infant affected by second-or third-degree atrioventricular block (AVB), 177 mothers with rheumatic disease having infants with normal heart rate and female blood donors (n = 136). A novel serological assay for Ro52 p200-antibodies with intra-and inter-assay variability of 3% and 3·8% respectively was developed. Mothers of children affected by AVB II-III had significantly higher p200-antibody levels than mothers with rheumatic disease having children with normal heart rate (P < 0·001). In the Swedish cohort, a distinction between foetuses with normal conduction, AVB I, AVB II and III was possible. A significant difference in anti-p200 levels between AVB I and AVB II-III groups compared with foetuses with normal conduction (P < 0·05 and P < 0·01) was observed. Using p200-antibodies as a second step analysis in Ro52-positive pregnancies increased the positive predictive value for foetal cardiac involvement (AVB I, II or III) from 0·39 (0·27-0·51) to 0·53 (0·37-0·68). In conclusion, Ro52 p200-antibodies may occur in women with unaffected children, but levels are significantly higher in mothers of children with congenital heart block and are suggested as a relevant marker in evaluating the risk for foetal AV block.

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

“…More recently, the response to peptides within the Ro-and La-proteins has also been examined (9,25,26). While this approach has provided new insights into the reasons for the low prevalence of cardiac NLE, it has little clinical utility as these assays are available in research facilities only.…”

Neonatal Lupus Erythematosus

“…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]. Although maternal anti Ro52-p200 antibody exposure was observed in equal frequency in both affected and unaffected offspring [17], higher levels of Ro52 p200 antibodies were observed in mothers of children with CHB compared to those with normal children [18]. Cutaneous NL was present in 16 % of women with anti-SSA/Ro antibodies and was significantly more frequent in those with both anti-SSA/Ro and anti-SSB/La autoantibodies [3].…”

Pregnancy implications for systemic lupus erythematosus and the antiphospholipid syndrome

“…Several aspects have been investigated, although many questions remain open. The features of maternal autoantibodies seem to be relevant [36]: i) specificity: antibodies to amino acid 200-239 (p200) of Ro52 were detected at higher titre in mothers of children with CHB [37]; ii) titre: levels of maternal anti-Ro/SSA antibodies were higher in those cases who had a child with cardiac complications. Genetics may be also important, since foetal susceptibility to cardiac NL has been shown to be associated with MHC-encoded genes [38]and with genes related to inflammatory and apoptotic responses that may promote cardiac damage triggered by maternal autoantibodies [39].…”