Genetics of Psoriasis and Autoimmune Disorders
Title: The genetics of psoriasis and autoimmunity.
Author: 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.
