Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2015 Jul 20;1(1):e000097.
doi: 10.1136/rmdopen-2015-000097. eCollection 2015.

Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease

Francesco Caso  1 , Paola Galozzi  2 , Luisa Costa  1 , Paolo Sfriso  2 , Luca Cantarini  3 , Leonardo Punzi  2
Affiliations
Review

Autoinflammatory granulomatous diseases: from Blau syndrome and early-onset sarcoidosis to NOD2-mediated disease and Crohn's disease

Francesco Caso et al. RMD Open. .

Abstract

The recent identification of genetic mutations leading to dysfunction of inflammatory and apoptotic pathways, has allowed to characterise a group of diseases, recognised as monogenic autoinflammatory syndromes. Among those, Blau syndrome (BS) and early-onset sarcoidosis (EOS) have been identified as familial and sporadic phenotypes of the same non-caseating granulomatous form. Both the diseases are caused by mutations in the CARD15/NOD2 gene, encoding the cytosolic NOD2 protein, one of the key molecules in the regulation of innate immunity. Clinical onset is typically located in the first years of life and phenotype is characterised by simultaneous or less articular, cutaneous and ocular non-caseating granulomatous inflammation, which can be variably associated with a heterogeneous systemic spectrum. The CARD15/NOD2 gene has also been identified as one of the genes linked to susceptibility to Crohn's disease (CD), a common polygenic inflammatory granulomatous bowel disease. The heightened nuclear factor-κB activity, found in the intestinal tissue of patients affected by CD, has probably a genetic cause related to several CARD15/NOD2 polymorphisms. Other substitutions in the CARD15/NOD2 gene have also been found in a recently described disorder, called NOD2-associated autoinflammatory disease, which shares several clinical characteristics with BS and EOS. This review attempts to describe these diseases on the basis of the most recent evidences. We described genetic and clinical aspects, mainly focusing on BS and EOS, the most representative diseases of autoinflammatory granulomatous diseases, with the ultimate purpose to expand their knowledge.

Keywords: Arthritis; Fever Syndromes; Inflammation.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic representation of the NOD2 protein (NP_071445.1) with the characteristic three domains structure and localisation of NOD2 mutations described in autoinflammatory granulomatous diseases. Red squares highlight mutations associated with BS, whereas the grey colour identifies EOS-related mutations, on the basis of the Infevers database data (CARD, caspase recruitment domain’ LRR, leucine rich repeat; NACHT, central nucleotide-binding and oligomerisation domain; http://fmf.igh.cnrs.fr/ISSAID/infevers/index.php).
Figure 2
Figure 2
Camptodactyly in a young patient affected with BS.
Figure 3
Figure 3
Anterior uveitis in a patient with BS showing fibrin at the level of the anterior chamber.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell 2002;10:417–26. 10.1016/S1097-2765(02)00599-3 - DOI - PubMed
    1. Masters SL, Simon A, Aksentijevich I et al. . Horror autoinflammaticus: the molecular pathophysiology of autoinflammatory disease. Annu Rev Immunol 2009;27:621–68. 10.1146/annurev.immunol.25.022106.141627 - DOI - PMC - PubMed
    1. Caso F, Costa L, Rigante D et al. . Caveats and truths in genetic, clinical, autoimmune and autoinflammatory issues in Blau syndrome and early onset sarcoidosis. Autoimmun Rev 2014;13:1220–9. 10.1016/j.autrev.2014.08.010 - DOI - PubMed
    1. Hugot JP, Chamaillard M, Zouali H et al. . Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn's disease. Nature 2001;411:599–603. 10.1038/35079107 - DOI - PubMed
    1. Yao Q, Zhou L, Cusumano P et al. . A new category of autoinflammatory disease associated with NOD2 gene mutations. Arthritis Res Ther 2011;13:R148 10.1186/ar3462 - DOI - PMC - PubMed