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Identification of discrete epitopes of Ro52p200 and association with fetal cardiac conduction system manifestations in a rodent model
University of Padua, Italy; Karolinska Institute, Sweden.
University of Padua, Italy.
Karolinska Institute, Sweden.
Karolinska Institute, Sweden.
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2016 (English)In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 186, no 3, 284-291 p.Article in journal (Refereed) Published
Abstract [en]

Congenital heart block (CHB) is a potentially lethal condition characterized by a third-degree atrioventricular block (AVB). Despite anti-Ro52 antibodies being detected in nearly 90% of mothers of affected children, CHB occurs in only 1-2% of anti-Ro/Sjogrens-syndrome-related antigen A (SSA) autoantibody-positive pregnancies. Maternal antibodies have been suggested to bind molecules crucial to fetal cardiac function; however, it remains unknown whether a single antibody profile associates with CHB or whether several specificities and cross-reactive targets exist. Here, we aimed to define further the reactivity profile of CHB-associated antibodies towards Ro52p200 (amino acid 200-239). We first analysed reactivity of a monoclonal anti-Ro52 antibody shown to induce AVB in rats (7.8C7) and of sera from anti-Ro52p200 antibody-positive mothers of children with CHB towards a panel of modified Ro52p200 peptides, and subsequently evaluated their potential to induce AVB in rats upon transfer during gestation. We observed that CHB maternal sera displayed a homogeneous reactivity profile targeting preferentially the C-terminal part of Ro52p200, in contrast to 7.8C7 that specifically bound the p200 N-terminal end. In particular, amino acid D233 appeared crucial to maternal antibody reactivity towards p200. Despite low to absent reactivity towards rat p200 and different binding profiles towards mutated rat peptides indicating recognition of different epitopes within Ro52p200, immunoglobulin (Ig)G purified from two mothers of children with CHB could induce AVB in rats. Our findings support the hypothesis that several fine antibody specificities and cross-targets may exist and contribute to CHB development in anti-Ro52 antibody-positive pregnancies.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2016. Vol. 186, no 3, 284-291 p.
Keyword [en]
anti-Ro52 antibodies; AV block; congenital heart block; neonatal lupus erythematosus; SSA
National Category
Immunology in the medical area
Identifiers
URN: urn:nbn:se:liu:diva-132979DOI: 10.1111/cei.12854ISI: 000387589200002PubMedID: 27548532Scopus ID: 2-s2.0-84992671972OAI: oai:DiVA.org:liu-132979DiVA: diva2:1054757
Note

Funding Agencies|Swedish Research Council; Swedish Heart-Lung Foundation; Stockholm County Council; Karolinska Institute; Swedish Rheumatism Association; King Gustaf the Vth 80-year Foundation; Freemason Children Foundation Stockholm; Torsten and Ragnar Soderberg Foundation

Available from: 2016-12-09 Created: 2016-12-07 Last updated: 2016-12-13

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Anandapadamanaban, MadhanagopalSunnerhagen, Maria
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Department of Physics, Chemistry and BiologyFaculty of Science & EngineeringChemistry
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