Structure and pathogenicity of antibodies specific for citrullinated collagen type II in experimental arthritis

Antibodies to citrulline-modifi ed proteins have a high diagnostic value in rheumatoid arthritis (RA). However, their biological role in disease development is still unclear. To obtain insight into this question, a panel of mouse monoclonal antibodies was generated against a major triple helical collagen type II (CII) epitope (position 359 – 369; ARGLTGRPGDA) with or without arginines modifi ed by citrullination. These antibodies bind cartilage and synovial tissue, and mediate arthritis in mice. Detection of citrullinated CII from RA patients ’ synovial fl uid demonstrates that cartilage-derived CII is indeed citrullinated in vivo. The structure determination of a Fab fragment of one of these antibodies in complex with a citrullinated peptide showed a surprising beta -turn conformation of the peptide and provided information on citrulline recognition. Based on these findings, we propose that autoimmunity to CII, leading to the production of antibodies specific for both native and citrullinated CII, is an important pathogenic factor in the development of RA

0228: Impact of the precision of prenatal diagnostic of congenital heart diseases on perinatal and long-term management

ObjectiveTo evaluate the impact of precising prenatal diagnosis of congenital heart diseases (CHD) on perinatal and long-term management.MethodsOver a 10-year period, 1258 neonates with a prenatally diagnosed CHD and 189 fetal autopsies after termination of pregnancy were included. Changes in CHD diagnosis were classified as totally different, similar but leading to changes in neonatal management, and similar without changes on initial management. The impact on long-term outcome was considered negative if the final diagnosis was a more complex CHD precluding the planned biventricular repair, or if additional surgical interventions were needed, or if the complexity level of the Aristotle score was increased. The impact on outcome was considered positive if biventricular repair was possible while not planned prenatally, or if the number of surgical interventions was reduced, or if the complexity level of the Aristotle score was lower.ResultsThe post-natal diagnosis was imprecise in 30.2% of the cases: completely different in 2.9%, led to changes in initial management in 8%, and did not affect initial management in 19.3%. Imprecision in the prenatal diagnosis had a negative impact on long-term outcome in 4.9% of the cases, and a positive impact in 4.1%.In the fetal autopsy group (mean term 26 weeks), the diagnosis was imprecise in 54.5% of the cases: completely different in 8.5%, could have led to changes in postnatal management in 14.3%, and with minor differences that would not have led to changes in management in 31.7%. In both groups, the most frequent differences were anomalies of the outflow tract anatomy (43%), and the systemic or pulmonary veins (25%).ConclusionImprecision of prenatal diagnosis of CHD changes early management in 11% of the cases, and impacts long-term outcome in 9% of the cases. Improvement of CHD diagnosis for anatomy of the outflow tract and main veins should help to reduce impact on postnatal management and outcome