Lessons from characterization and treatment of the autoinflammatory syndromes

Curr Opin Rheumatol. 2017 Mar;29(2):187-194. doi: 10.1097/BOR.0000000000000362.


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.

Publication types

  • Review

MeSH terms

  • Antirheumatic Agents / therapeutic use*
  • Arthritis, Juvenile / drug therapy
  • Arthritis, Juvenile / genetics
  • Colchicine / therapeutic use*
  • Endopeptidases / genetics
  • Familial Mediterranean Fever / drug therapy
  • Familial Mediterranean Fever / genetics
  • Haploinsufficiency
  • Hereditary Autoinflammatory Diseases / drug therapy*
  • Hereditary Autoinflammatory Diseases / genetics
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use*
  • Intracellular Signaling Peptides and Proteins
  • Mevalonate Kinase Deficiency / drug therapy
  • Mevalonate Kinase Deficiency / genetics
  • Phosphotransferases (Alcohol Group Acceptor) / genetics
  • Proteins / genetics
  • Pyrin / genetics
  • Tubulin Modulators / therapeutic use*
  • Tumor Necrosis Factor alpha-Induced Protein 3 / genetics


  • Antirheumatic Agents
  • Interleukin 1 Receptor Antagonist Protein
  • Intracellular Signaling Peptides and Proteins
  • LACC1 protein, human
  • MEFV protein, human
  • Proteins
  • Pyrin
  • Tubulin Modulators
  • Phosphotransferases (Alcohol Group Acceptor)
  • mevalonate kinase
  • Endopeptidases
  • OTULIN protein, human
  • TNFAIP3 protein, human
  • Tumor Necrosis Factor alpha-Induced Protein 3
  • Colchicine