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Updated: Aug 19, 2025

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Macroglobulinemia and Autoinflammatory Disease.

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  • 1Division of Rheumatology, Allergy and Immunology, Stony Brook University Renaissance School of Medicine, Stony Brook, NY, USA.

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|December 5, 2022
PubMed
Summary

Schnitzler syndrome (SchS) and Waldenstrom macroglobulinemia (WM) share clinical traits and potential genetic links. Myeloid differentiation primary response gene 88 (MyD88) and nucleotide-binding oligomerization domain containing protein 2 (NOD2) mutations may contribute to SchS.

Keywords:
MyD88NOD2Schnitzler syndromeWaldenstrom macroglobulinemiaautoinflammatory diseasemacroglobulinemia

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Area of Science:

  • Immunology and Genetics
  • Rheumatology and Hematology

Background:

  • Schnitzler syndrome (SchS) is a rare autoinflammatory condition.
  • Waldenstrom macroglobulinemia (WM) is a lymphoproliferative disorder.
  • Both SchS and WM share overlapping clinical phenotypes, with SchS potentially progressing to WM.

Purpose of the Study:

  • To review the clinical aspects of Schnitzler syndrome and Waldenstrom macroglobulinemia.
  • To explore potential genetic links between SchS and WM.
  • To investigate the role of specific gene mutations in the pathogenesis of SchS.

Main Methods:

  • Literature review using PubMed.
  • Keywords included: SchS, WM, autoinflammatory disease, periodic fever syndrome, NOD2.
  • Analysis of genetic mutations in SchS and WM patients.

Main Results:

  • Myeloid differentiation primary response gene 88 (MyD88) mutations found in one-third of SchS patients and 86% of WM patients.
  • Nucleotide-binding oligomerization domain containing protein 2 (NOD2) mutations detected in 18% of SchS patients.
  • NLRP3 mutations were rarely found in SchS patients.

Conclusions:

  • MyD88 and NOD2 mutations are suggested to contribute to the development of Schnitzler syndrome.
  • These genes play critical roles in innate immune response and may be cooperative in autoinflammatory diseases.
  • Incorporating molecular analysis of NOD2 mutations into genetic testing for suspected SchS or SchS/WM is recommended.