Serum type I interferon activity is dependent on maternal diagnosis in anti‐SSA/Ro–positive mothers of children with neonatal lupus

Abstract

Objective. The type I interferon (IFN) pathway is activated in many patients with systemic lupus erythematosus (SLE), and high serum levels of IFN are associated with anti-SSA/Ro autoantibodies. To investigate the clinical features associated with type I IFN production in vivo, we compared serum IFN activity in individuals with anti-SSA/Ro antibodies who were asymptomatic with that in individuals with clinical manifestations of SLE or Sjögren's syndrome (SS).Methods. Antibody-positive sera from 84 mothers of children with manifestations of neonatal lupus were studied for type I IFN activity, using a functional reporter cell assay. Maternal health status was characterized as asymptomatic, SS, SLE, pauci-SLE, or pauci-SS, based on a screening questionnaire, telephone interview, and review of medical records. The prefix "pauci-" indicates symptoms insufficient for a formal classification of the disease.Results. Only 4% of asymptomatic mothers had high serum type I IFN activity, compared with 73% with pauci-SLE (P ‫؍‬ 5.7 ؋ 10 ؊5 ), 35% with SLE (P ‫؍‬ 0.011), and 32% of patients with SS (P ‫؍‬ 0.032). One of the 4 patients with pauci-SS had high levels of IFN. The majority of patients for whom longitudinal data were available had stable type I IFN activity over time, and changes in IFN activity were not clearly accompanied by changes in the clinical diagnosis.Conclusion. Patients with SLE, patients with pauci-SLE, and patients with SS are more likely to have high serum IFN activity than asymptomatic individuals with SSA/Ro autoantibodies, suggesting that these autoantibodies are insufficient for activation of the type I IFN pathway, and that disease-specific factors are important for type I IFN generation in vivo.

Activation of the type I interferon pathway in primary Sjogren’s syndrome

“…Commercial ELISAs have not been informative for quantification of type I IFN activity in the systemic circulation of these patients. However, the development of highly sensitive cell reporter assays by our group and others has allowed the demonstration of the presence of detectable type I IFN activity in the sera or plasmas of pSS patients [22,23]. In our hands, the use of a monoclonal antibody against IFNa fully abrogated type I activity, implying the presence of IFNa in the circulation of these patients.…”

What to Expect When Expecting With Systemic Lupus Erythematosus (SLE): A Population‐Based Study of Maternal and Fetal Outcomes in SLE and Pre‐SLE

“…Our study supports the idea that the underlying immunologic profile of subclinical SLE may be associated with a higher likelihood of adverse maternal and fetal outcomes. For example, autoantibodies (anti‐SSA/Ro) in patients with insufficient clinical symptoms to be classified as SLE have increased levels of interferon‐α, and interferon‐α increases maternal vascular susceptibility to preeclampsia 19, 20.…”

Association of IRF5 polymorphisms with activation of the interferon α pathway

“…Interestingly, high serum IFNα activity is not associated with ANA or anti-SSA/Ro antibody positivity in subjects without disease manifestations,29 30 suggesting these are independent variables in the development of SLE. The correlation between IFN-inducible gene expression in peripheral blood cells and lupus disease activity and flare,31–36 however, implicates the IFNα pathway specifically in the development and exacerbation of SLE.…”