E086 Clinical and serological features of increased interferon-alpha activity in an unselected connective tissue disease cohort

John Reynolds (1) , Tracy Briggs (1) , Gillian Rice (1) , Sathya Darmalinggam (1) , Vincent Bondet (2) , Ellen Bruce (1) , Mumtaz Khan (1) , Sahena Haque (1) , Hector Chinoy (1) , Ariane Herrick (1) , Eoghan Mccarthy (1) , Leo Zeef (1) , Andrew Hayes (1) , Darragh Duffy (2) , Ben Parker (1) , Ian Bruce (1)

1 University of Manchester [Manchester]
2 Immunobiologie des Cellules dendritiques

Background: The connective tissue diseases (CTDs) are currently defined by common clinical features rather than the underlying immunopathological abnormalities. Interferon-alpha (IFNα) is an important pro-inflammatory cytokine implicated in autoimmunity and may be increased in some CTD patients. We aimed to determine the clinical and serological features of a high IFNα subgroup of patients within an unselected CTD cohort. Methods: We recruited patients with at least 1 CTD clinical feature, and at least 1 CTD-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 high-sensitivity digital ELISA 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 (⩾2 s.d. of a healthy control cohort). The 3 measures of IFNα all correlated strongly with each other (p < 0.0001). The ISG-positive group had increased frequency of ever having had a haematological abnormality, and lower contemporaneous leukocyte counts, which remained significant after adjusting for the CTD subtype (Table 1).

Domains: Life Sciences [q-bio]

John Reynolds, Tracy Briggs, Gillian Rice, Sathya Darmalinggam, Vincent Bondet, et al.. E086 Clinical and serological features of increased interferon-alpha activity in an unselected connective tissue disease cohort. Rheumatology, 2019, 58 (Supplement_3), ⟨10.1093/rheumatology/kez110.084⟩. ⟨pasteur-03251882⟩