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Background / PurposeIdentification 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).MethodsClinical 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). Results21% 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<0.001, odds ratio [OR] 7.1 95% confidence interval [CI] 3-17). When comparing anti-p140 and anti-p155/140 cases; cutaneous oedema (p=0.04) and rash over the trunk (p=0.002) and small joints (p=0.013) was more frequent with anti-p155/140. Calcinosis in anti-p140 remained a significant feature compared to anti-p155/140 (p=0.005, OR 6.4 95% CI 2-22). HLA-DRB1*08 was a significant risk factor in anti-p140 positives (25%) compared to controls (5%) (OR 5.8 95% CI 2-18, corrected p=0.002).ConclusionAnti-p140 found in our cohort is likely to be the same as anti-MJ, recently described to target nuclear matrix protein NXP-2 [2] and further confirmation is required. Anti-p140 is a major autoantibody subset in JDM and is associated with HLA-DRB1*08. Further characterisation of this system may provide insights into the pathophysiology of calcinosis and JDM.References1. Gunawardena H et al. Clinical associations of autoantibodies to a p155/140 kDa doublet in juvenile dermatomyositis. Rheumatology 2008;47:324-8.2. Targoff IN et al. Sera with autoantibodies to the MJ antigen react with NXP2. Arthritis Rheum 2007;56 Suppl 9:S787.

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