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Lessons from characterization and treatment of the autoinflammatory syndromes

Aksentijevich, Ivona; McDermott, Michael F.

Current Opinion in Rheumatology: March 2017 - Volume 29 - Issue 2 - p 187–194
doi: 10.1097/BOR.0000000000000362
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Purpose of review: The list of genes associated with systemic inflammatory diseases has been steadily growing because of the explosion of new genomic technologies. Significant advances in the past year have deepened our understanding of the molecular mechanisms linked to inflammation and elucidated insights on the efficacy of specific therapies for these and related conditions. We review the molecular pathogenesis of four recently characterized monogenic autoinflammatory diseases: haploinsufficiency of A20, otulipenia, a severe form of pyrin-associated disease, and a monogenic form of systemic juvenile idiopathic arthritis.

Recent findings: The scope of autoinflammation has been broadened to include defects in deubiquitination and cellular redox homeostasis. At the clinical level, we discuss the biological rationale for treatment with cytokine inhibitors and colchicine in respective conditions and the use of interleukin-1 antagonism for diagnostic and therapeutic purposes in the management of undifferentiated autoinflammatory disorders.

Summary: Gene discoveries coupled with studies of molecular function provide knowledge into the biology of inflammatory responses and form the basis for genomically informed therapies. Diseases of dysregulated ubiquitination constitute a novel category of human inflammatory disorders.

aInflammatory Disease Section, National Human Genome Research Institute, Bethesda, Maryland, USA

bNIHR National Institute for Health Research–Leeds Musculoskeletal Biomedical Research Unit (NIHR-LMBRU) and Leeds Institute of Rheumatic and Musculoskeletal Medicine (LIRMM), Wellcome Trust Brenner Building, St. James's University Hospital, Leeds, UK

Correspondence to Dr Ivona Aksentijevich, NHGRI/NIH, Bldg.10 CRC Rm. B2-5235, 9000 Rockville Pike, Bethesda, MD 20892, USA. Tel: +1 301 496 8365; fax: +1 301 480 2490; e-mail:

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