SCIENTIFIC BACKGROUND

NLRP3

Category:

Cryopyrin-associated periodic syndromes (CAPS) include three disorders that were formerly classified separately:

 

  • Familial cold-associated syndrome (FCAS)
  • Muckle-Wells syndrome (MWS)
  • Neonatal-onset multisystem inflammatory disease (NOMID) (also called chronic infantile neurological cutaneous and articular syndrome, CINCA)

 

Since variants in the NLRP3 gene (also NALP3/CIAS1) have been identified as the cause of all three syndromes, it is thought that these disorders represent different degrees of clinical severity of the same pathophysiological change. CAPS are inherited in an autosomal dominant manner; in NOMID, mutations occur predominantly de novo. All ethnic groups can be affected by CAPS. In Germany, 2-7 newly diagnosed patients (aged ≤ 16 years) are estimated per year. The first striking manifestation is an urticaria-like skin rash that develops shortly after birth (NOMID) or in early childhood (all three disorders). In addition, episodes of fever occur, usually accompanied by arthralgias, headache, fatigue, and conjunctivitis. In FCAS, the febrile episodes are triggered by exposure to cold and usually last up to 24 hours. MWS is characterized by the development of progressive sensorineural hearing loss as the disease progresses (often not until adolescence). About 25% of MWS patients develop secondary amyloidosis if untreated. NOMID presents with the most severe phenotype of CAPS. Facial abnormalities such as a prominent forehead and saddle nose deformity are described, and neurological and movement symptoms are typical. Postnatally, chronic progressive aseptic meningitis, sensorineural hearing loss, and optic atrophy often develop. The therapy of choice in CAPS is targeted IL-1 blockade.

 

The NLRP3 gene product cryopyrin is a key component of the cryopyrin inflammasome, a cytoplasmic protein complex formed as part of the innate immune response that induces IL-1β production. Variants in the NLRP3 gene, presumably through constitutive activation of cryopyrin, lead to increased production of IL-1β even in the absence of exogenous stimuli. Almost all the mutations known to date are located in exon 3 of the NLRP3 gene. However, in approximately 40-60% of patients with classic clinical manifestations of NOMID syndrome, no mutations are found in the entire coding region of the NLRP3 gene.

 

References

Gattorno et al. 2019, Ann Rheum Dis Epub ahead of print, doi:10.1136 / Booshehri & Hoffman 2019, J Clin Immunol 39:277 / Cuisset et al. 2011, Ann Rheum Dis 70:495 / Lainka et al. 2010, Klin Padiatr 222:356

GENES

NLRP3
How to order

LATEST ARTICLES

February, designated as Cancer Awareness Month, marks a time to reflect on the remarkable progress made in cancer research and to inspire hope for th...

Read more

Introduction Cardiovascular disease (CVD) is a major health issue as it remains a leading cause of death worldwide [1]. CVD is responsible for mor...

Read more

Antimicrobial resistance (AMR) is one of the most pressing global health threats, and accurate identification and surveillance of multidrug-resistant...

Read more

Colorectal cancer remains a significant health concern globally. While genetic factors play a crucial role in its development, identifying the exact ...

Read more

A new meta-analysis links trans-kingdom gut microbiota (bacteria, eukaryotes, viruses, archaea) to immune checkpoint inhibitor (ICI) response in canc...

Read more

Reproductive health is a fundamental aspect of human well-being, affecting individuals and communities worldwide [1]. It encompasses a wide range of ...

Read more

It seems as though everyone is talking about artificial intelligence, usually referred to as AI, these days! Indeed, not only are AI tools now access...

Read more

Orphan drugs are those developed specifically for the treatment of rare diseases. Within the pharmaceutical industry, the drug development process is...

Read more

A study of 629 pregnancies with ultrasound-detected anomalies found that exome sequencing identified pathogenic variants in 14% of cases. The detecti...

Read more

Breast cancer is a type of cancer that originates in the breast cells. Genetic changes in the DNA of the healthy breast cells can lead to the formati...

Read more