The roles of interferon biomarkers in monitoring patients with systemic lupus erythematosus and other connective tissue diseases

Background: Type I interferon (IFN-I) is thought to have a central role in the pathogenesis and activity of autoimmune connective tissue disease (CTD). As a heterogeneous condition, CTD is often a challenge to manage, which is further made difficult by the lack and imprecision in diagnostic tools. IFN has shown promise as biomarkers in correlation studies on disease activity in CTD. Real world challenges in CTD management could be addressed with a validated IFN biomarker.
Objectives: (i) to examine the role of IFN biomarkers in the prediction of flares and glucocorticoid requirements in SLE; (ii) to examine the use IFN assays in distinguishing patients who meet definite CTD classification criteria from a cohort of patients labelled as UCTD; and (iii) to examine the relationship between IFN biomarkers and patient-reported outcomes in patients At-Risk, with UCTD and with established CTD.
Methods: A prospective study was conducted in a (i) SLE cohort and a (ii) UCTD cohort attending routine clinics. Comprehensive clinical assessment focussing on (i) disease activity and glucocorticoid requirements, and (ii) classification criteria for SLE, SS, IM and SSc, was conducted in conjunction with IFN biomarker sampling. (iii) A cross-sectional study of patient-reported outcomes was administered together with IFN biomarker sampling in At-Risk, UCTD and established CTD patients attending routine clinic.
Results: (i) High IFN Score A, IFN Score B and Memory B cell tetherin were associated with flares and increased glucocorticoid requirements in a cohort of SLE patients; (ii) IFN Score A was higher in those who were re-classified into CTD than those remained undifferentiated, thus could be used to distinguish between these two groups, and patient’s initially labelled as UCTD; (iii) correlation between IFN Scores and PROMs varied widely among diagnoses of CTDs, with the strongest correlation found in patients with UCTD.
Conclusion: In this thesis, I have demonstrated several potential uses of IFN assays in the monitoring of patients with CTD with respect to prediction of flares and glucocorticoid requirements in SLE; the distinguishment of classifiable CTD from UCTD; and understanding the relationships between IFN and patient-reported outcomes. These findings need validation in a longitudinal cohort to inform their applicability in clinical practice.