Related Experiment Videos
Influence of HLA-DR2, HLA-DPw4, and T cell receptor alpha chain genes on the susceptibility to multiple sclerosis
M A Sherritt1, J Oksenberg, N K de Rosbo
1Neuroimmunology Laboratory, La Trobe University, Bundoora, Victoria, Australia.
Abstract:
In view of our recent report that T cell receptor (TCR) alpha chain restriction fragment length polymorphism (RFLP) is associated with multiple sclerosis (MS), we have assessed the possibility that HLA-DR2, HLA-DPw4, and TCR alpha chain RFLPs may interact to increase the risk of developing MS. Detection of TCR alpha chain polymorphisms, and HLA-DR and -DP typing were carried out by RFLP analysis on MS patients and healthy controls from the Melbourne metropolitan area. Interaction effects among these loci in producing susceptibility to MS were assessed by hierarchial log-linear analysis. Although HLA-DR2 was significantly associated with MS (chi 2 = 9.30, P = 0.002), no interactive effect between MS and HLA-DPw4 was observed. Significant interactions were observed with MS and both C alpha and V alpha, with the strongest effect seen with C alpha (chi 2 = 21.30, P less than 0.001). The combination of DR2/C alpha imparted a relative risk of 47. However, when the data were analysed for four and three way interactions, no significant effects were seen with MS, DR2, DPw4, V alpha, and C alpha, implying that the combined presence of these polymorphic markers is not essential for increasing susceptibility to MS.
Insights
Multiple sclerosis (MS) risk is linked to T cell receptor (TCR) alpha chain polymorphisms, particularly C alpha, and HLA-DR2. While these factors increase risk, their combined presence isn't essential for MS development.
Area of Science:
- Immunogenetics
- Neurology
- Human Genetics
Background:
- Previous research indicated a link between T cell receptor (TCR) alpha chain restriction fragment length polymorphism (RFLP) and multiple sclerosis (MS).
- The potential interaction between human leukocyte antigen (HLA) variants (HLA-DR2, HLA-DPw4) and TCR alpha chain RFLPs in MS susceptibility required further investigation.
Purpose of the Study:
- To investigate the interactive effects of HLA-DR2, HLA-DPw4, and TCR alpha chain RFLPs on the risk of developing multiple sclerosis (MS).
Main Methods:
- Restriction fragment length polymorphism (RFLP) analysis was used for TCR alpha chain typing and HLA-DR/DP typing in MS patients and healthy controls.
- Hierarchical log-linear analysis was employed to assess interaction effects among these genetic loci and MS susceptibility.
Main Results:
- HLA-DR2 showed a significant association with MS (P = 0.002).
- Significant interactions were found between MS and TCR alpha chain polymorphisms, specifically C alpha (P < 0.001) and V alpha.
- The combination of HLA-DR2 and C alpha demonstrated a high relative risk (47) for MS.
Conclusions:
- TCR alpha chain polymorphisms, particularly C alpha, interact with HLA-DR2 to significantly increase the risk of multiple sclerosis.
- No significant four- or three-way interactions were observed, suggesting that the combined presence of all studied polymorphic markers is not mandatory for MS susceptibility.