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

John A. Reynolds (1) , Tracy Briggs (1, 2) , Gillian Rice (1) , Sathya Darmalinggam (1) , Vincent Bondet (3) , Ellen Bruce (1) , Mumtaz Khan (1) , Sahena Haque (1) , Hector Chinoy (1, 4) , Ariane Herrick (1, 4) , Eoghan Mccarthy (1) , Leo Zeef (1) , Andrew Hayes (1) , Darragh Duffy (3) , Ben Parker (1) , Ian Bruce (1)

1 University of Manchester [Manchester]
2 MCGM - Manchester Centre for Genomic Medicine [Manchester, UK]
3 Immunobiologie des Cellules dendritiques
4 Salford Royal NHS Foundation Trust [Salford, UK]

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.

Mots clés: Autoantibodies; Interferon alpha; Systemic autoimmune rheumatic disease

Domaines: Immunologie

John A. Reynolds, Tracy Briggs, Gillian Rice, Sathya Darmalinggam, Vincent Bondet, et al.. Type I interferon in patients with systemic autoimmune rheumatic disease is associated with haematological abnormalities and specific autoantibody profiles. Arthritis Research and Therapy, 2019, 21 (1), pp.147. ⟨10.1186/s13075-019-1929-4⟩. ⟨pasteur-02173399⟩