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FRI0309 Type I Interferon Activity Is Associated with Mucocutaneous but Not Musculoskeletal Disease Activity in Systemic Lupus Erythematosus
  1. A.A.A. Mohamed1,2,3,
  2. Y. El-Sherbiny1,2,
  3. E.M. Hensor1,2,
  4. M.Y. Md Yusof1,2,
  5. S.H. Goma4,
  6. E.A. Abda4,
  7. F.M. Abd-Allah4,
  8. P. Emery1,2,
  9. E. Vital1,2
  1. 1NIHR Leeds Musculoskeletal Biomedical Research Unit, Leeds Teaching Hospitals NHS Trust
  2. 2Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, United Kingdom
  3. 3Rheumatology and Rehabilitation Department
  4. 4Assiut University, Assiut, Egypt

Abstract

Background SLE is clinically and immunologically heterogeneous. Type I interferons (IFN-I) are pathogenic but expression of IFN-I stimulated genes varies. Many existing reports on clinical phenotype and IFN-I were limited by using categorical measures of IFN-I and disease activity scores that were not organ-specific. IFN-I targeted therapies are in development.

Objectives To define the clinical phenotype of IFN-I mediated SLE.

Methods 108 SLE patients and 20 age and sex matched healthy controls were studied. Activity was measured using BILAG-2004. PBMCs were collected for gene expression analysis using TaqMan. Relative expression of 7 interferon stimulated genes was In-transformed, normalized to healthy control and summed to derive a 7-gene IFN-I score.

Results The most common activity was mucocutaneous and musculoskeletal, which were analysed in detail (Table 1). The relationship between activity and IFN-I score differed between these domains. Overall, IFN-I scores were higher in active mucocutaneous disease. Scores were more variable for BILAG B: this was explained by subtype of BILAG B disease. IFN-I score was increased in subacute and discoid forms (25.3 (16.8–32.9), n=7) compared to acute forms (18.4 (4.9–31), n=15). Score was also higher in patients with anti-Ro60. In contrast, there was no relationship between musculoskeletal disease activity and IFN-I score.

Numbers of patients with renal, haematological and neuropsychiatric activity were limited but there was a trend to higher IFN-I scores with disease activity.

Conclusions We identify a relationship between clinical presentation of SLE and IFN-I. High IFN-I activity is linked to anti-Ro60 and non-acute forms of skin disease. We previously reported a worse response to rituximab in this subgroup, whilst response in musculoskeletal disease was consistently good. Measurement of B cell and interferon biomarkers may therefore be important in the selection of the most appropriate targeted therapy for SLE.

Disclosure of Interest None declared

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