Brief Report: IFIH1 Mutation Causes Systemic Lupus Erythematosus With Selective IgA Deficiency. Issue 6 (June 2015)

• Record Type: Journal Article
• Authors: Van Eyck, Lien; De Somer, Lien; Pombal, Diana; Bornschein, Simon; Frans, Glynis; Humblet‐Baron, Stéphanie; Moens, Leen; de Zegher, Francis; Bossuyt, Xavier; Wouters, Carine; Liston, Adrian
• Is Part Of: Arthritis & rheumatology. Volume 67:Issue 6(2015)
• Page Start: 1592
• Page End: 1597
• Publication Date: 2015-06
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; 616.72
• DOI: 10.1002/art.39110
• Languages: English
• ISSNs: 2326-5191

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="art39110-sec-0001" sec-type="section"> <title>Objective</title> <p>To identify the underlying genetic defect in a 16‐year‐old girl with severe early‐onset and refractory systemic lupus erythematosus (SLE), IgA deficiency, and mild lower limb spasticity without neuroradiologic manifestations.</p> </sec> <sec id="art39110-sec-0002" sec-type="section"> <title>Methods</title> <p>Whole‐exome sequencing and extensive immunologic analysis were performed on samples from the index patient.</p> </sec> <sec id="art39110-sec-0003" sec-type="section"> <title>Results</title> <p>We identified a de novo p.R779H <italic>IFIH1</italic> gain‐of‐function mutation in a patient with severe early‐onset SLE, selective IgA deficiency, and mild lower limb spasticity. The same mutation in <italic>IFIH1</italic> was recently identified in patients with Aicardi‐Goutières syndrome, a rare neuroimmunologic disorder associated with elevated levels of type I interferon (IFN). IFN induced with helicase C domain 1 functions as an intracellular innate immune receptor that senses viral nucleic acids and leads to the induction of type I IFN and proinflammatory cytokines. Despite systemic immunosuppressive treatment, disease activity persisted in the patient and was associated with elevated serum levels of IFNα and up‐regulation of <italic>IFIH1</italic> itself.</p> </sec> <sec id="art39110-sec-0004" sec-type="section"> <title>Conclusion</title> <p>This finding adds a new genetic causation for Mendelian lupus and greatly extends the disease spectrum associated with mutations in <italic>IFIH1</italic> (ranging from inflammatory encephalopathy to prototypic systemic autoimmune disease). This marked phenotypic heterogeneity, despite an identical mutation, demonstrates the importance of modifying factors in type I IFN–dependent pathologies caused by mutations in <italic>IFIH1</italic>.</p> </sec> </abstract>