Inverse Relation between MxA Gene Expression and Age in Multiple Sclerosis Patients Reveals a Gender Difference in Response to Interferon Therapy

Abstract

Multiple sclerosis (MS) is an inflammatory, multifocal, immune-mediated disease of the central nervous system that women are at a higher risk to acquire than men. Myxovirus resistance protein A (MxA) is used as a predictive marker of bioactivity of interferon-beta (IFN-β) therapy in MS patients. This study was undertaken in west of Iran to investigate gender differences in the expression level of MxA in relapsing-remitting MS (RRMS) patients receiving IFN-β therapy, compared with untreated normal individuals. The expression level of the MxA gene in RRMS samples were compared to untreated normal individuals using the extracted RNA from whole blood of 50 RRMS patients (31 females and 19 males) and 50 normal controls (29 females and 21 males). All patients were HLA-DRB1*15 negative and responded to IFN-β with a normal vitamin D level. The level of MxA gene expression was measured by quantitative RT-PCR. The levels of gene expression were decreased in RRMS patients compared with normal counterparts (p=0.025). This decrease was significant in females (p=0.009) compared to males (p>0.05). The level of expression varied across different female age-groups with no significant difference in women younger than 30 years, but a significant decrease in expression in women between 30 to 40 years or above 40 years of age was seen. There was neither linear correlation between the MxA expression level and risk of expanded disability status scale of Kurtzke (EDSS); nor were there any significant correlation between expression status of MxA and duration of the disease. In conclusion, the decrease in the level of MxA expression in MS patients treated with IFN-β when compared to normal individuals was significantly lower in females than males. This demonstrated a gender bias in the response to IFN-β therapy that will need to be confirmed and further investigated in more detail.

Keywords

• Gene expression
• Interferon-beta
• Multiple sclerosis
• Mx1