Novel Autoantibodies targeting a p140 protein are a major autoantigen system in juvenile dermatomyositis and a marker of calcinosis

H Gunawardena, LR Wedderburn, H Chinoy, ZE Betteridge, J North, WER Ollier, RG Cooper, AV Ramanan, JE Davidson, NJ McHugh

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

Background / Purpose Identification of novel autoantigen targets in juvenile dermatomyositis (JDM) may lead to the identification of more homogeneous clinical and immunogenetic subsets within the disease spectrum, have prognostic implications and lead to further insights into pathogenesis. The aim of this study was to demonstrate that autoantibodies targeting a p140 singlet protein are a major autoantigen in JDM. We describe the clinical and immunogenetic associations of anti-p140 autoantibodies in children recruited to the JDM National Registry and Repository (UK and Ireland). Methods Clinical data and sera were collected from 156 children recruited to the registry. Serum was screened by immunofluorescence (IF) and radio-immunoprecipitation of [35S]-methionine labelled K562 cells (IPP). [1]. Immunodepletion was performed to establish whether p140 is a different target to p155/140 which is also recognised in this JDM cohort [1]. DNA from 100 children was genotyped for HLA-DRB1 (using a commercially available sequence specific oligonucleotide kit) and compared to 864 randomly selected UK Caucasian controls. The study had the appropriate ethical approval. Subjects gave informed written or parental consent. Clinical features were compared using the appropriate statistical tests (SPSS ver.14). Results 21% of children were positive for anti-p140 on IPP, with a weak non-specific nuclear pattern or negative ANA on IF. No anti-p140 cases were positive for other autoantibody specificities. Immunodepletion confirmed that p140 and p155/140 are different autoantigens. Anti-p140 positives compared to negatives had a similar male:female ratio and age at diagnosis. No significant difference was observed in the type or distribution of rash when comparing anti-p140 positives with negatives except for more rash on the trunk in negative cases (p=0.017). Calcinosis was significantly more frequent in anti-p140 positives (52%) compared to negatives (13%) (p
Original languageEnglish
Title of host publicationARTHRITIS AND RHEUMATISM
Place of PublicationHOBOKEN, NJ 07030 USA
PublisherJohn Wiley & Sons Ltd
PagesS923-S923
Volume58
Publication statusPublished - Sep 2008
Event72nd Annual Scientific Meeting of the American-College-of-Rheumatology - San Francisco, CA
Duration: 24 Oct 200829 Oct 2008

Conference

Conference72nd Annual Scientific Meeting of the American-College-of-Rheumatology
CitySan Francisco, CA
Period24/10/0829/10/08

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