title: Increased serum type I interferon activity in organ-specific autoimmune disorders: clinical, imaging, and serological associations.
abstract: BACKGROUND
  Activation of the type I interferon (IFN) pathway has been implicated in the pathogenesis of systemic autoimmune disorders but its role in the pathogenesis of organ-specific autoimmunity is limited. We tested the hypothesis that endogenous expression of type I IFN functional activity contributes to the pathogenesis of autoimmune thyroid disease (ATD) and type I diabetes (T1DM).
  
  
  METHODS
  We studied 39 patients with ATD and 39 age and sex matched controls along with 88 T1DM patients and 46 healthy matched controls respectively. Available clinical and serological parameters were recorded by chart review, and thyroid ultrasound was performed in 17 ATD patients. Type I IFN serum activity was determined in all subjects using a reporter cell assay. The rs1990760 SNP of the interferon-induced helicase 1 gene was genotyped in ATD patients.
  
  
  RESULTS
  Serum type I IFN activity was increased in patients with ATD and T1DM compared to controls (p-values: 0.002 and 0.04, respectively). ATD patients with high type I IFN serum activity had increased prevalence of antibodies against thyroglobulin (anti-Tg) and cardiopulmonary manifestations compared to those with low IFN activity. Additionally, the presence of micronodules on thyroid ultrasound was associated with higher type I IFN levels. In patients with T1DM, high IFN levels were associated with increased apolipoprotein-B levels.
  
  
  CONCLUSIONS
  Serum type I IFN activity is increased in ATD and T1DM and is associated with specific clinical, serological, and imaging features. These findings may implicate type I IFN pathway in the pathogenesis of specific features of organ-specific autoimmunity.
authors: Mary Kirkland Center for Lupus Research, Hospital for Special Surgery , New York, NY , USA ; Department of Physiology, School of Medicine, University of Athens , Athens , Greece.
authors: Clio P
authors: CP
authors: Mavragani
authors: Timothy B
authors: TB
authors: Niewold
authors: Antonis
authors: A
authors: Chatzigeorgiou
authors: Stamatina
authors: S
authors: Danielides
authors: Dimitrios
authors: D
authors: Thomas
authors: Kyriakos A
authors: KA
authors: Kirou
authors: Elli
authors: E
authors: Kamper
authors: Grigorios
authors: G
authors: Kaltsas
authors: Mary K
authors: MK
authors: Crow
keywords: autoimmune thyroid disease; organ-specific autoimmunity; type I diabetes; type I interferon
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