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NOD2-associated autoinflammatory disease: a large cohort study.

Qingping Yao1, Min Shen2, Christine McDonald3

  • 1Department of Rheumatic and Immunologic Disease, qingpingyao@yahoo.com.

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|June 14, 2015
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Summary

Nucleotide-binding oligomerization domain containing 2 (NOD2)-associated autoinflammatory disease (NAID) is linked to specific NOD2 variants, differing from Crohn's disease. This genetic disorder may be more prevalent than previously recognized.

Keywords:
Crohn’s diseaseIVS8+158NOD2-associated autoinflammatory diseasenucleotide-binding oligomerization domain containing 2 (NOD2)

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Area of Science:

  • Genetics
  • Immunology
  • Dermatology

Background:

  • Autoinflammatory diseases represent a group of disorders characterized by dysregulated innate immunity.
  • Nucleotide-binding oligomerization domain containing 2 (NOD2) is a key intracellular pattern recognition receptor involved in immune responses.
  • NOD2-associated autoinflammatory disease (NAID) is a rare condition linked to variations in the NOD2 gene.

Purpose of the Study:

  • To characterize the genotype profile of patients with NAID.
  • To investigate the association between NOD2 variants and NAID.
  • To describe the clinical phenotype and epidemiology of NAID.

Main Methods:

  • Genotyping of 143 adult patients with suspected NAID for NOD2 sequence variants.
  • Comparison of genotype frequencies with historical control data.
  • Clinical data collection including demographics, age at onset, disease duration, and presenting symptoms.

Main Results:

  • 47% of patients carried NOD2 variants, a significantly higher frequency than in controls.
  • Fifty-four patients with NOD2 variants were diagnosed with NAID.
  • NAID patients, predominantly non-Jewish white women, presented with periodic fever, dermatitis, and arthritis, with distinct skin manifestations and distal lower extremity swelling compared to NOD2 variant-negative patients.
  • Commonly associated NOD2 variants included IVS8(+158) and compound variants R702W/IVS8(+158).

Conclusions:

  • NAID is a genetically complex, multisystem disorder associated with NOD2 variants.
  • NAID exhibits a distinct genotype profile and phenotypic differences compared to Crohn's disease.
  • The prevalence of NAID may be underestimated.