Patients at risk of autoimmune connective tissue disease who progressed to actual disease had elevated interferon scores and a family history of autoimmune rheumatic disease, suggesting the interferon scores could be used to predict disease progression, according to results from a prospective, observational study published in Annals of the Rheumatic Diseases.

Md Yuzaiful Md Yusof, MBChB, of the Institute of Rheumatic and Musculoskeletal Medicine at the University of Leeds (England) and his colleagues evaluated long-term data from musculoskeletal ultrasound and blood and skin biopsy samples of 118 patients at risk of developing autoimmune connective tissue disease (AI-CTD). They compared exams and samples from baseline as well as 12 months, 24 months, and 36 months against data from 49 healthy patients and 114 patients with systemic lupus erythematosus (SLE). Patients were at risk of developing AI-CTD if they had one or fewer symptoms of clinical SLE, displayed symptoms for less than 12 months, were antinuclear antibody (ANA) positive, and had not been treated previously for AI-CTD. The researchers analyzed blood and biopsy results for two continuous interferon (IFN) expression scores, IFN-Score-A and IFN-Score-B.

“Referrals of ANA-positive individuals to rheumatologists has increased over the last decade. Concerns are that these at-risk individuals may be discharged prematurely or be observed in an inefficient ‘watch and wait’ fashion until the diagnosis is clear, by which time the potential to prevent disease and confer the most benefit may be lost,” Dr. Yusof and his colleagues wrote in their study.

There were 19 of 118 patients who progressed to AI-CTD after 12 months of follow-up; of these patients, 14 developed SLE and 5 developed primary Sjögren’s syndrome. The researchers noted no significant differences among baseline characteristics or findings from ultrasound, compared with other groups. Compared with healthy controls, IFN-Score-A increased in 105 at-risk patients (fold difference = 2.21; 95% confidence interval, 1.22-4.00; P = .005) and in all 114 patients in the SLE group (fold difference = 7.81; 95% CI, 4.33-14.04; P less than .001). IFN-Score-A was also increased in the SLE group, compared with the at-risk group (fold difference = 3.54; 95% CI, 2.22-5.63; P less than .001). For IFN-Score-B, there was no difference between rates in the healthy control group and the at-risk group. However, IFN-Score-B was increased in the SLE group, compared with the healthy control group (fold difference = 3.85; 95% CI, 2.60-5.72; P less than .001) and the at-risk group (fold difference = 3.93; 95% CI, 2.87-5.37; P less than .001).

Independent baseline predictors of AI-CTD progression in a multivariate analysis included family history of autoimmune rheumatic disease (odds ratio, 8.20; P = .012) and IFN-Score-B (OR, 3.79; P = .005), researchers said.

“Although we could not confirm which IFN pathways predominate, our findings suggest that progression to AI-CTD may not be exclusively driven by IFN-I [type I interferon] but by a synergistic activation of [interferon-stimulated genes] induced by a range of IFNs and IFN-Score-B [that] could act as a biomarker for more diverse immune activation,” Dr. Yusof and his colleagues wrote.

Dr. Yusof is a U.K. National Institute for Health Research doctoral fellow at the University of Leeds. Several other authors reported financial support from range of pharmaceutical companies.

SOURCE: Yusof MYM et al. Ann Rheum Dis. 21 Jun 2018. doi: 10.1136/annrheumdis-2018-213386.

Autoimmune connective tissue disease predicted by interferon status, family history