Autoimmune phenotype with type I interferon signature in two brothers with ADA2 deficiency carrying a novel CECR1 mutation

作者：Skrabl Baumgartner Andrea^*; Plecko Barbara; Schmidt Wolfgang M; Koenig Nadja; Hershfield Michael; Gruber Sedlmayr Ursula; Lee Kirsch Min Ae

来源：Pediatric Rheumatology, 2017, 15(1): 67.

DOI：10.1186/s12969-017-0193-x

• Adenosine deaminase 2
• CECR1
• Systemic lupus erythematosus
• Hypergammaglobulinaemia
• Antinuclear antibodies
• Interferon signature

Background: Loss-of-function CECR1 mutations cause polyarteritis nodosa (PAN) with childhood onset, an autoinflammatory disorder without significant signs of autoimmunity. Herein we describe the unusual presentation of an autoimmune phenotype with constitutive type I interferon activation in siblings with adenosine deaminase 2 (ADA2) deficiency.
Case presentation: We describe two siblings with early-onset recurrent strokes, arthritis, oral ulcers, discoid rash, peripheral vascular occlusive disease and high antinuclear antibody titers. Assessment of interferon signatures in blood revealed constitutive type I interferon activation. Aicardi-Goutieres syndrome (AGS) was suspected, but no mutation in the known AGS genes were detected. Whole exome sequencing identified compound heterozygosity for a known and a novel mutation in the CECR1 gene. Functional consequences of the mutations were demonstrated by marked reduction in ADA2 catalytic activity.
Conclusions: Our findings demonstrate that ADA2 deficiency can cause an unusual autoimmune phenotype extending the phenotypic spectrum of PAN. Constitutive interferon I activation in patient blood suggests a possible role of type I interferon in disease pathogenesis which may have therapeutic implications.

• 出版日期2017-8-22