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Emerging insights into mosaic errors of immunity.

Willem Roosens1, Jonas Demeulemeester2, Eric Legius3

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Summary

Mosaic errors of immunity (MEI) are immune disorders from gene variants affecting blood cells. This review synthesizes MEI knowledge, offering a framework to understand these rare genetic disorders and immune pathways.

Keywords:
hematoinflammationimmunogeneticsmosaic errors of immunityprimary immune regulatory disorderssomatic mosaicism

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Area of Science:

  • Immunology
  • Genetics
  • Hematology

Background:

  • Mosaic errors of immunity (MEI) are immune disorders caused by somatic or gonosomal gene variants affecting hematopoiesis and immune function.
  • The role of mosaicism in monogenic immune disorders is known, but pathogenesis, genotype-phenotype correlation, and clonal evolution are poorly understood.

Purpose of the Study:

  • To synthesize molecular determinants of recognized MEI.
  • To provide a mechanistic framework for future research on MEI.
  • To explore implications of mosaic genetic variation in unexplained immune disorders.

Main Methods:

  • Literature review and synthesis of existing data on MEI.
  • Analysis of molecular determinants and genetic variation.
  • Mechanistic framework development.

Main Results:

  • Shared and distinct molecular determinants across recognized MEI have been identified.
  • A mechanistic framework for understanding MEI pathogenesis and evolution is proposed.
  • Potential for uncovering novel genetic disorders and understanding immune pathways.

Conclusions:

  • Further research into mosaic genetic variation can reveal new actionable genetic disorders.
  • Studying MEI offers insights into cell-specific immune pathways, non-malignant clonal dynamics, and mosaic disorders.
  • Understanding MEI is crucial for advancing both immunology and genetics.