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Two-factor interferon score, family history predict connective tissue disease progression
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Physicians and rheumatologists can use a two-factor interferon score and family history to predict a patient’s progression from being antinuclear-antibody positive to developing autoimmune connective tissue diseases, such as systemic lupus erythematosus or Sjögren’s syndrome, according to findings published in the Annals of the Rheumatic Diseases.
“[Antinuclear antibodies] can be detected in serum up to 10 years before clinical features, representing a phase of subclinical autoimmunity,” Md Yuzaiful Md Yusof, MBChB, MRCP, of the University of Leeds, England, and colleagues wrote. “However, [antinuclear antibodies] are present in up to 25% of the general population, of whom less than 1% develop clinical autoimmunity. Individuals with [antinuclear antibodies] therefore constitute at-risk population of whom a minority will progress to [autoimmune connective tissue diseases].”
“Variants in type I interferon (IFN-I) pathway are prominent in the genetic susceptibility to [autoimmune connective tissue diseases] and therefore a focus for investigation,” Md Yusof and colleagues added. “However, their role in disease initiation is currently unclear.”
To analyze the clinical, interferon and imaging predictors of progressing from “at risk” status to developing autoimmune connective tissue diseases, the researchers conducted a prospective, observational study of patients referred from primary care to Leeds Teaching Hospitals NHS Trust, who were suspected of having autoimmune connective tissue disease between November 2014 and May 2017. For this study, “at risk” for autoimmune connective tissue disease was defined as being antinuclear-antibody positive, having one or fewer clinical SLE criteria, experiencing symptoms for less than 12 months and being treatment-naive.
A total of 118 at-risk participants with 12-month follow-ups were included in the study. In addition, the researchers enrolled 49 healthy individuals and 114 patients with SLE as negative and positive controls, respectively. Md Yusof and colleagues analyzed blood and skin biopsy for IFN-Score-A and IFN-Score-B. Progression was defined as meeting classification criteria for autoimmune connective tissue diseases at 12 months.
According to the researchers, among the 118 at-risk participants, 16% progressed to autoimmune connective tissue diseases, with 14 developing SLE and five ultimately diagnosed with Sjögren’s syndrome. Both IFN scores differed among the at-risk, healthy control and SLE control groups at baseline (P < .001). In addition, both scores were elevated among those at-risk participants who eventually progressed to autoimmune connective tissue disease at 12 months, compared with those who did not progress. Among those who progressed, IFN-Score-B was particularly elevated (fold difference of 3.22; 95% CI, 1.74-5.95) compared to IFN-Score-A (2.94; 95% CI, 1.14-7.54).
Participants who progressed did not have significantly greater baseline clinical characteristics or ultrasound findings, the researchers wrote. After completing multivariable logistic regression, the researches noted that only a family history of autoimmune rheumatic disease (OR = 8.2; 95% CI, 1.58-42.53) and IFN-Score-B (OR = 3.79; 95% CI, 1.5–9.58) increased the odds of progression.
“A novel [interferon-stimulated gene] score, IFN-Score-B and family history of [autoimmune rheumatic diseases] predict progression from [antinuclear-antibody] positivity to [autoimmune connective tissue diseases],” Md Yusof and colleagues wrote. “After validation, the predictive value of IFN scores may allow us to identify patients with imminent [autoimmune connective tissue diseases] for earlier intervention using therapies that block IFNs or conventional immunosuppressants to avoid irreversible organ damage and glucocorticoid exposure. Additionally, patients with benign autoreactivity can be better identified.” – by Jason Laday
Disclosure: Md Yusof reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.
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