Clinical and serological manifestations associated with interferon-α levels in childhood-onset systemic lupus erythematosus

Abstract

OBJECTIVE:To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features.METHODS:We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay.RESULTS:We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33±4.50), 64 first-degree relatives (mean age 39.95±5.66), and 57 healthy (mean age 19.30±4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels.CONCLUSION:Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.

Childhood onset systemic lupus erythematosus: how is it different from adult SLE?

“…Polymorphisms in genes involved in IFN‐alpha pathway, for example IFN regulatory factor 5 and non‐receptor tyrosine‐protein kinase (TYK2) also support its role . Further, a recent study has shown a direct correlation between SLE Disease Activity Index (SLEDAI) scores and IFN‐alpha levels, suggesting that IFN‐alpha signature can serve as a new biomarker for SLE disease activity . Based on the role of IFN in SLE pathogenesis, several therapies targeting the IFN‐alha pathway are currently in clinical trials …”

Fueling autoimmunity: type I interferon in autoimmune diseases

“…Lupus patients contain circulating IFN and “IFN signature” – transcript expression of a panel of type I IFN-responsive genes - in their peripheral blood, which frequently correlate with the disease severity [5–9]. In childhood-onset systemic lupus erythematosus, the levels of serum IFNα is positively correlated with circulating anti-dsDNA autoantibodies and SLE Disease Activity index scores [10]. Not only 90% of pediatric SLE patients and more than 50% of adult patients display peripheral IFN signature, half of the biopsied glomeruli from SLE kidneys also contain IFN-inducible transcripts, suggesting a central role played by IFN-mediated pathogenesis [10,11].…”

“…In childhood-onset systemic lupus erythematosus, the levels of serum IFNα is positively correlated with circulating anti-dsDNA autoantibodies and SLE Disease Activity index scores [10]. Not only 90% of pediatric SLE patients and more than 50% of adult patients display peripheral IFN signature, half of the biopsied glomeruli from SLE kidneys also contain IFN-inducible transcripts, suggesting a central role played by IFN-mediated pathogenesis [10,11]. As a prototypic systemic autoimmune disease, SLE has been extensively studied in recent years and significant knowledge has been acquired regarding the source of IFN, the innate immune signaling pathways underlying its induction, and genetic risk factors involved (discussed in following sections).…”

Defining Biological Subsets in Systemic Lupus Erythematosus: Progress Toward Personalized Therapy

“…Polymorphisms in interferon regulatory factor (IRF) 5, IRF7, STAT4, and other known SLE-risk loci have been associated with the production of particular autoantibodies [44, 49–52], further supporting the case that autoantibody formation in SLE has a genetic component, and that subsets of patients defined by autoantibodies are genetically different. In previous work, we have shown that many first-degree relatives of SLE patients had significantly higher serum IFN-α levels compared to healthy unrelated individuals [53, 54]. These data suggest that IFN-α is a heritable risk factor in SLE, and thus genetic factors which lead to high IFN-α may be concentrated in lupus families [53].…”