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Defective production of interferon-alpha associated with HLA-DW2 antigen in stable multiple sclerosis
Abstract:
Interferon (IFN) production by peripheral blood mononuclear cells after induction with one purified and three crude viral antigens was studied in 29 patients with stable multiple sclerosis (MS) and 29 healthy controls. Antiviral substance produced was characterized as interferon-alpha. MS patients produced significantly less IFN-alpha after induction with mumps and purified measles virus antigens and the same tendency was seen after induction with rubella virus antigen. However, when herpes simplex virus antigen was used as the stimulating agent, no difference was seen between MS patients and controls. The decreased ability to produce IFN-alpha was associated with the histocompatibility antigen Dw2. Control subjects positive for Dw2 also produced less IFN-alpha than Dw2-negative controls. In conclusion, we suggest that the observed impaired interferon-alpha production in MS is at least partially due to a high prevalence of Dw2 antigen in this disease.
Insights
Multiple sclerosis patients show reduced interferon-alpha production in response to certain viral antigens. This impairment is linked to the presence of the Dw2 histocompatibility antigen, suggesting a partial cause for the condition.
Area of Science:
- Immunology
- Virology
- Neurology
Background:
- Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system.
- Interferon-alpha (IFN-α) plays a crucial role in antiviral immunity.
- Dysregulation of immune responses is implicated in MS pathogenesis.
Purpose of the Study:
- To investigate interferon-alpha production in patients with multiple sclerosis compared to healthy controls.
- To determine if viral antigen stimulation affects IFN-α production differently in MS patients.
- To explore the association between IFN-α production and specific histocompatibility antigens in MS.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) were isolated from 29 stable MS patients and 29 healthy controls.
- PBMCs were stimulated with purified and crude viral antigens (mumps, measles, rubella, herpes simplex virus).
- Interferon-alpha levels in the supernatant were quantified to assess IFN-α production.
Main Results:
- MS patients exhibited significantly lower IFN-α production after stimulation with mumps and measles virus antigens.
- A similar trend of reduced IFN-α production was observed with rubella virus antigen in MS patients.
- No significant difference in IFN-α production was found between MS patients and controls when stimulated with herpes simplex virus antigen.
- Impaired IFN-α production was associated with the presence of the histocompatibility antigen Dw2, observed in both MS patients and Dw2-positive controls.
Conclusions:
- Patients with multiple sclerosis demonstrate an impaired capacity to produce interferon-alpha in response to specific viral stimuli.
- The decreased IFN-α production in MS is at least partially attributed to the high prevalence of the Dw2 antigen.
- The findings suggest a potential role for immune dysregulation, specifically related to IFN-α and Dw2, in the pathophysiology of multiple sclerosis.