Genetics of Psoriasis and Autoimmune Disorders

Title: The genetics of psoriasis and autoimmunity.
: Bowcock AM
Publication: Annu Rev Genomics Hum Genet. 2005;6:93-122.

Psoriasis is an inflammatory / autoimmune disease (where the body’s own immune system attack its own body parts), and is associated genetically with major histocompatibility complex (MHC).

However, penetrance or the frequency of manifestation of physical symptoms in those with MHC-associated gene is not 100%. This may be because development of the symptoms requires additional environmental and/or genetic modifiers, or may require specific T-cell receptor arrangements. Families with genetic susceptibility to psoriasis other than MHC have also been reported.

Overlapping genetic locations of different autoimmune diseases have been known for several years and are starting to reveal common genes. These include genes that:

  • Prevent spontaneous T-cell activation or proliferation
  • Immune synapse formation or interaction of two types of immune system cells
  • Cytokine production via pathways such as those mediated by NFkappaB

Autoimmune disorders may also involve the RUNX family of transcription factors, which are involved in:

  • Hematopoietic or blood cell development
  • Development of T-cells in the thymus
  • Remodeling of chromatin or DNA and protein complex in the nucleus
  • Gene silencing

The authors concluded that the effect of MHC on cells of the immune system may be due to variable changes in gene expression and could account for the variable location of the psoriasis lesions and the waxing and waning of the disease.

Editor’s Note: T-cells or T-lymphocytes are white blood cells that mature in the thymus and can recognize specific peptide sequence through receptors on their surface. These cells orchestrate the immune system’s response to infected or malignant cells.

Transcription factors are proteins that bind the DNA at a specific region of a gene, and regulate the transcription of that gene into mRNA, which in turn is used to make proteins.

Cytokine is a type of protein that mediates immune response. NFkappaB or Nuclear Factor kappa B is a B-cell transcription factor that is involved in cellular response to cytokine, free radicals, uv light, bacteria, and viruses.

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