Article Text

PDF
OP0271 Analysis of the Autoantibody Repertoire in Idiopathic Inflammatory Myopathies Using Antigen Bead Array
  1. A. Notarnicola1,
  2. C. Mattsson2,
  3. H. Idborg1,
  4. C. Hellström2,
  5. E. Jemseby1,
  6. P.-J. Jacobsson1,
  7. P. Nilsson2,
  8. I.E. Lundberg1
  1. 1Department of Medicine, Rheumatology Unit, Karolinska University Hospital
  2. 2SciLifeLab, School of Biotechnology, KTH, Royal Institute of Technology, Solna, Stockholm, Sweden

Abstract

Background The Idiopathic Inflammatory Myopathies (IIM), including Polymyositis (PM), Dermatomyositis (DM) and Inclusion Body Myositis (IBM), are a group of rare systemic inflammatory diseases often associated with severe organ manifestations and premature mortality [1]. The identification of new biomarkers is needed to understand underlying biological pathways, improve diagnosis, predict prognosis and tailor treatment to the single patient.

Objectives We investigated EDTA-plasma samples of IIM patients and healthy controls (HC) to discover new myositis-associated auto-antigens.

Methods Planar antigen microarrays consisting of 5760 human protein fragments were used for the screening of IgG reactivity in 160 samples of patients with Systemic Lupus Erythematosus (SLE) [2]. A set of 355 antigens (Ag) was selected for verification on suspension bead array using 695 SLE samples and 278 IIM samples. The IIM samples were collected from a cohort of 245 IIM patients (91 DM, 125 PM and 29 IBM) regularly followed at the Rheumatology Unit of the Karolinska University Hospital from January 2003 until March 2014. Twenty-eight IIM patients tested positive for anti-hystidyl-tRNA-synthetase antibodies (anti-Jo-1) and 217 were anti Jo-1 negative. Samples from 41 HC were also analysed.

Results Reactivity towards 70% of the 355 selected Ag was observed in more than 2% of both IIM and HC samples. Comparing the IIM and the HC groups according to the number of samples which showed reactivity towards each single Ag, reactivity towards 3 Ag was discovered with higher frequencies in the IIM samples (Fisher exact test, p<0.05). We also compared each IIM subset and HC. A higher number of DM and PM samples versus HC showed reactivity towards 4 and 3 Ag, respectively. No statistically significant difference was observed between IBM and HC samples for any of the 355 Ag. Making 2 group comparisons between DM/PM/IBM subsets, a statistically significant different reactivity profile was found for 1 Ag between DM and PM, 3 Ag between DM and IBM and 4 Ag between PM and IBM. The number of reactive samples towards 5 Ag was significantly higher in the anti-Jo-1 positive compared to the anti-Jo-1 negative patients.

Conclusions Auto-antigen reactivity was present both in IIM and HC samples. IIM and HC samples showed different frequencies of reactivity towards some of the selected Ag. A validation analysis is ongoing to confirm our preliminary results.

References

  1. Dalakas MC. Polymyositis, dermatomyositis and inclusion-body myositis. N Engl J Med. 1991;325:1487–98.

  2. B. Ayoglu et al., Expert Rev Mol Diagn 11, 219 (Mar, 2011).

Disclosure of Interest A. Notarnicola: None declared, C. Mattsson: None declared, H. Idborg: None declared, C. Hellström: None declared, E. Jemseby: None declared, P.-J. Jacobsson Grant/research support from: Astra-Zeneca, P. Nilsson: None declared, I. E. Lundberg Grant/research support from: Novartis, Servier, Astra-Zeneca och Bristol-Myers Squibb

Statistics from Altmetric.com

Request permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.