Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles

Research output: Contribution to journalArticle

  • External authors:
  • Sathya Darmalinggam
  • Vincent Bondet
  • Ellen Bruce
  • Mumtaz Khan
  • Sahena Haque
  • Eoghan Mccarthy
  • Leo Zeef
  • Andrew Hayes
  • Darragh Duffy
  • Benjamin Parker
  • Ian Bruce

Abstract

Objectives To investigate the relationships between interferon-alpha (IFNα) and the clinical and serological phenotype of patients with systemic autoimmune rheumatic disease (SARDs) in order to determine whether a distinct subpopulation of patients can be identified. Methods We recruited patients with at least 1 SARD clinical feature, and at least 1 SARD-related autoantibody from two NHS Trusts in Greater Manchester. A 6-gene interferon-stimulated gene (ISG) score was calculated in all patients and in a subgroup, a 30-gene ISG score was produced using NanoString. A digital Single Molecule Array (Simoa) was used to measure plasma IFNα protein. In an exploratory analysis, whole blood RNA sequencing was conducted in 12 patients followed by RT-qPCR confirmation of expression of 6 nucleic acid receptors (NARs) in the whole cohort. Results Sixty three of 164 (38%) patients had a positive ISG score. The 3 measures of IFNα all correlated strongly with each other (p<0.0001). There were no differences in mucocutaneous or internal organ involvement between the ISG subgroups. The ISG-positive group had increased frequency of specific autoantibodies and haematological abnormalities which remained significant after adjusting for the SARD subtype. Expression of DDX58, MB21D1 and TLR7 was correlated with the ISG score whilst TLR3, TLR9 and MB21D1 were associated with neutrophil count. Conclusion In SARD patients, IFNα-positivity was associated with specific autoantibodies and haematological parameters but not with other clinical features. The variable NAR expression suggests that different pathways may drive IFNα production in individual patients. The identification of an IFNα-positive subgroup within a mixed SARD cohort supports a pathology-based approach to treatment.

Bibliographical metadata

Original languageEnglish
Article number147
JournalArthritis Research and Therapy
Volume21
Issue number1
DOIs
Publication statusPublished - 2019

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