52-kDa Ro/SSA epitopes preferentially recognized by antibodies from mothers of children with neonatal lupus and congenital heart block

Christine Fritsch¹ , Johan Hoebeke¹ , Hayet Dali¹ , Vincent Ricchiuti¹^,2 , David A Isenberg³ , Olivier Meyer⁴ and Sylviane Muller¹

¹UPR 9021 Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, Strasbourg, France

²Division of Endocrinology, Diabetes & Hypertension, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA

³Centre for Rheumatology, The Middlesex Hospital, University College London, UK

⁴Groupe Hospitalier Bichat-Claude Bernard, Service de Rhumatologie, Paris, France

author email corresponding author email

Arthritis Research & Therapy 2006, 8:R4doi:10.1186/ar1848


Published:	4 November 2005

Abstract

Neonatal lupus erythematosus is a rare disorder caused by the transplacental passage of maternal autoantibodies. The 52-kDa Ro/SSA antigen (Ro52) ribonucleoprotein represents an antigenic target strongly associated with the autoimmune response in mothers whose children have neonatal lupus and cardiac conduction disturbances, mainly congenital heart block. The objective of this study was to identify putative Ro52/60-kDa Ro/SSA antigen (Ro60) epitopes associated with neonatal lupus and congenital heart block. The reactivity of IgG antibodies present in the sera from mothers with systemic lupus erythematosus and Sjögren's syndrome and in the sera from asymptomatic mothers (a longitudinal study of 192 samples from 66 subjects) was investigated by ELISA using Ro52, Ro60 and 48-kDa La/SSB antigen proteins, as well as 45 synthetic peptides, 13–24 residues long, of Ro52/Ro60 proteins. One to 19 samples collected before, during and after pregnancy were available for each mother. Forty-three disease controls selected randomly and normal sera were tested in parallel. Although no differences were found between Sjögren's syndrome and asymptomatic mothers of group I, who had at least one infant with neonatal lupus, and of group II, who had healthy babies only, significant differences were observed between lupus mothers from both groups. In the former group of lupus mothers, a significantly higher frequency of antibodies to Ro52 peptides 107–122 and 277–292 was observed. Between 18 and 30 weeks of gestation, the period of risk, there was clearly an elevated level of antibodies reacting with Ro52 peptides 1–13, 277–292 and 365–382. Antibodies to Ro52 peptide 365–382 have been shown previously to cross-react with residues 165–185 of the heart 5-HT₄serotoninergic receptor, and might be pathologically important. The level of these Ro52 antibody subsets decreased at the end of pregnancy and after delivery. IgG antibodies to Ro52 peptides 1–13, 107–122, 277–292 and 365–382 may therefore represent important biomarkers to predict a complication in pregnant lupus women with Ro52 antibodies.