Immunodeficiency, autoinflammation and amylopectinosis in humans with inherited HOIL-1 and LUBAC deficiency Academic Article uri icon


MeSH Major

  • Glycogen Storage Disease Type IV
  • Hereditary Autoinflammatory Diseases
  • Immunologic Deficiency Syndromes
  • NF-kappa B
  • Ubiquitin-Protein Ligases


  • We report the clinical description and molecular dissection of a new fatal human inherited disorder characterized by chronic autoinflammation, invasive bacterial infections and muscular amylopectinosis. Patients from two kindreds carried biallelic loss-of-expression and loss-of-function mutations in HOIL1 (RBCK1), a component of the linear ubiquitination chain assembly complex (LUBAC). These mutations resulted in impairment of LUBAC stability. NF-κB activation in response to interleukin 1β (IL-1β) was compromised in the patients' fibroblasts. By contrast, the patients' mononuclear leukocytes, particularly monocytes, were hyper-responsive to IL-1β. The consequences of human HOIL-1 and LUBAC deficiencies for IL-1β responses thus differed between cell types, consistent with the unique association of autoinflammation and immunodeficiency in these patients. These data suggest that LUBAC regulates NF-κB-dependent IL-1β responses differently in different cell types.


publication date

  • December 2012



  • Academic Article



  • eng

PubMed Central ID

  • PMC3514453

Digital Object Identifier (DOI)

  • 10.1038/ni.2457

PubMed ID

  • 23104095

Additional Document Info

start page

  • 1178

end page

  • 86


  • 13


  • 12