Patients with previously diagnosed monogenic inflammatory diseases and non-immunologically determined phenotypes that were associated with type I IFN signaling were tested. Controls were selected from a diverse group without preexisting medical conditions. Samples from parents and siblings of patients with autosomal dominant interferonopathies who were themselves negative for the mutation were collected. 

Methodology of Crowe Article

6 interferon stimulated genes (ISGs)--IFI127, IFI44L, IFIT1, ISG15, RSAD2 and SIGLEC1-- were greatly expressed in a cohort of patients with Aicardi-Goutieres syndrome (AGS). The median fold change of the six ISGs in relation to the median of 29 controls was used to construct an IS for every patient. This publication supports the theory that upregulated type I IFN signaling is an effective biomarker for inflammatory clinical phenotypes. Additionally, repeat testing of the expression of these novel genes can aid in identification of new ISGs and type I interferonopathies. 

Type I IFN Signaling in Known ISGs

Samples were collected from 41 patients with AID and 27 patients displayed no evidence of upregulation of type I interferon signaling. This implies the accuracy of the interferon signature as a diagnostic tool, suggesting that autoinflammation can have molecular sources in both interferon and non-interferon pathways. 

Interferon Signature (IS) & Auto-Inflammatory Disorders (AID)

Dr. Crowe and colleagues published data supporting the use of an Interferon Score (IS) to diagnose patients with type I interferonopathies and determine the efficacy of therapeutics for these inflammatory disorders. These assays can identify the relationship between type I interferonopathies and interferon stimulated genes (ISGs) to develop an interferon score that alerts clinicians to the immunological mechanisms of interferonopathies. 

Tulane University

Certain mendelian disorders are associated with upregulation of IFN production, resulting in inflammatory phenotypes. Disturbances to the homeostatic maintenance of this system can result in illnesses similar to lupus erythematosus (SLE) and dermatomyositis (DM). 

Type I Interferonopathies

Rice GI, Melki I, Frémond ML, Briggs TA, Rodero MP, Kitabayashi N, Oojageer A, Bader-Meunier B, Belot A, Bodemer C, Quartier P, Crow YJ. Assessment of Type I Interferon Signaling in Pediatric Inflammatory Disease. J Clin Immunol. 2017 Feb;37(2):123-132. doi: 10.1007/s10875-016-0359-1. Epub 2016 Dec 9. PMID: 27943079; PMCID: PMC5325846.

Learn Before

Related

Learn After