Custom Ankylosing Spondylitis Panel

What is ankylosing spondylitis?

Ankylosing spondylitis (AS) is a chronic condition characterized by inflammation between the vertebrae in the spine as well as between the spine and the ankle joint, which can cause initial bone and joint erosion and induce joint stiffness. The pathogenesis of AS is related to genetic factors, immune factors and environmental factors. Studies have shown that the mutation of human leukocyte antigen B27 (HLA-B27) increases the risk of AS, and the prevalence of HLA-B27 positive individuals with family history of AS is 6-16 times as much as that of HLA-B27 positive individuals with no family history. After human CD4⁺T cells are stimulated by antigen, different cytokines are induced to differentiate into different subpopulations. The activation imbalance of two subtypes of Th1/Th2 is associated with inflammatory responses in a variety of autoimmune diseases. The pathogenesis of AS is associated with the increase in Th1 cytokines and the decrease in Th2 cytokines, but the role of specific Th1/Th2 cell populations, particularly Th1, in the pathogenesis of AS remains unclear. What’s more, studies have shown that the expression of TLR-4 in peripheral blood of patients with AS is elevated, suggesting that bacterial infection may be an important factor in the pathogenesis of AS.

Disease-related gene description

The main physiological function of HLA-B27 is to present endogenous antigenic peptides to CD8⁺T cells, which are generally considered to be involved in the restricted recognition of T cells. Some studies believe that, under normal circumstances, HLA B27 is transferred to the cell surface in a fully folded mature state, but HLA-B27 is found to be slow to fold in the AS animal model. The reason may be that a large amount of unfolded protein accumulates in the endoplasmic reticulum and cannot be transported to the cell surface. The endoplasmic reticulum overload reaction activates related proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin (IL)-2, leading to the onset of AS. In addition to the recognized variation in the HLA-B27 gene, which is thought to be closely related to AS, there are other important candidate genes that are also associated with AS, mainly including HLA-B14, HLA-B60, HLA-B39, MMP3, TNF-α, TGF-β, HSP-70, IL-1, IL-Ira, LMP2, CYP2DG, etc. In addition, studies have shown that polymorphisms of ERAP1 affect the risk of AS disease in HLA-B27 positive individuals.

In order to better explore the relationship between gene changes and the occurrence and progression of ankylosing spondylitis, and to promote the development of targeted therapy, CD Genomics’ custom ankylosing spondylitis panel platform offers a comprehensive library of ankylosing spondylitis panels, from which you can choose for genetic testing of ankylosing spondylitis.

Custom ankylosing spondylitis panel offers but not limited to:

Targeted DNA sequencing technology by Illumina MiSeq system/Ion PGM system provides ultra-deep sequencing for target specific genomic regions, so that we can detect low frequency ankylosing spondylitis variants.
Every detected genetic variant will be further validated to ensure the validity of results.
Strict quality control throughout the pipeline workflow ensures the accuracy and repeatability of the sequencing.
Custom panel content is designed to keep up with the frontiers from current literature about ankylosing spondylitis panel to target all relevant regions.
You can choose the panel content from our ankylosing spondylitis panel library or discuss with us to add the genes you interested in but are not in the panel, then we can provide you with your own panel.

Choose genes that suit you from the ankylosing spondylitis gene list

CYP2DG	ERAP1	HLA-B14
HLA-B27	HLA-B39	HLA-B60
HSP-70	IL1A	IL-1Ra
IL23R	LMP2	MMP3
TNF-α	TGF-β

Specimen requirements of our custom ankylosing spondylitis panel

Specimen: blood, saliva or extracted DNA (not FFPE-compatible).
Volume: 5 mL blood, 2 mL saliva, 3ug DNA.
Collection: blood is collected by routine blood collection and saliva is collected by saliva collection kits (kits are available upon request). DNA samples are stored in TE buffer or equivalent.
Container: lavender-top (EDTA) tube or yellow-top (ACD) tube.

Gene panel workflow

For more information about the Custom Ankylosing Spondylitis Panel or need other amplification requirements, please contact us.

References:

Laval S H, et al. Whole-genome screening in ankylosing spondylitis: evidence of non-MHC genetic-susceptibility loci. The American Journal of Human Genetics, 2001, 68(4): 918-926.
Evans D M, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nature genetics, 2011, 43(8): 761.
Dangoria N S, et al. HLA-B27 misfolding is associated with aberrant intermolecular disulfide bond formation (dimerization) in the endoplasmic reticulum. Journal of Biological Chemistry, 2002, 277(26): 23459-23468.
Evans D M, et al. Interaction between ERAP1 and HLA-B27 in ankylosing spondylitis implicates peptide handling in the mechanism for HLA-B27 in disease susceptibility. Nature genetics, 2011, 43(8): 761.

* For Research Use Only. Not for use in diagnostic procedures.