Good Immune Responses to CMV Infection Linked to Better Outcomes

Patients with such responses are more likely to experience slower MS progression

Margarida Maia, PhD avatar

by Margarida Maia, PhD |

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People with good immune responses against the human cytomegalovirus (CMV), a common herpes virus, around the time of their first symptoms of multiple sclerosis (MS) may go on to have a slower disease course, a study has found.

Compared with people showing weaker immune responses to CMV, these patients were less likely to reach a significant level of disability and to progress to secondary progressive MS (SPMS), and required more time before starting a disease modifying therapy.

The study, “Increased cytomegalovirus immune responses at disease onset are protective in the long-term prognosis of patients with multiple sclerosis,” was published in the Journal of Neurology, Neurosurgery and Psychiatry.

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Epstein-Barr virus raises risk of developing MS

The exact causes behind MS remain unclear, but being infected with the Epstein-Barr virus (EBV) raises the risk of developing the disease by more than 30 times. EBV is a member of the herpes virus family that may cause infectious mononucleosis, although it is commonly accompanied by unnoticeable symptoms. After an infection, the virus remains in the body, where it may lay latent throughout life.

While EBV increases with the risk of MS, it remains unknown whether this or other viral infections can affect disease progression in people with MS. This is difficult to determine, the researchers noted, because it would call for studies following patients over a long period of time.

To overcome this limitation, a team of researchers in Spain and Germany drew on data from 143 people with clinically isolated syndrome, a first presentation of MS symptoms, who were followed up for a median 20.1 years. There were 106 women and 37 men, and their mean age at the time of first symptoms was 29.9 years.

To determine how fast the disease was progressing in the patients, the researchers recorded the time it took for patients to reach certain disability milestones — namely an Expanded Disability Status Scale (EDSS) score of 3, which indicates moderate disability; a score of 4, indicating significant disability; and a score of 6, at which point patients require a walking aid to walk short distances.

They also recorded the time it took for patients to transition to SPMS and to require first-line or second-line MS treatment.

A total of 41 patients reached an EDSS of 3.0 after a median of 10.9 years, and 18 reached an EDSS of 4.0 after a median 16.9 years. Five patients reached an EDSS of 6.0 after a median 13.5 years. 

Seventeen patients went on to develop SPMS after a median 16 years. Data about first-line treatment were available for 137 patients and showed that 68 of them received first-line treatment after a median 3.2 years. Second-line treatment was given to 24 out of 140 patients with available data.

Analyses showed that the levels of immunoglobulin G antibodies against CMV at disease onset were significantly higher among those who did not reach a significant level of disability, progress to SPMS, or receive first-line treatment.

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Better immune responses to CMV linked to lower risk of disability progression

In fact, people who mounted better immune responses to infection with CMV had a 4.4% lower risk of reaching a score of 4.0 on the EDSS and 5.3% lower risk of progressing to SPMS. It also took them longer to be started on first-line treatment.

“These results indicate that elevated immune responses against [CMV] at disease onset have protective effects on long-term disability and inflammation disease outcomes,” the researchers wrote, adding that measuring antibody levels at the time of disease onset may help “identify patients with MS with more benign disease courses,” they added.

The study also showed an association between immune responses to EBV and disease outcomes, but most of the associations lost significance after accounting for a number of clinical and demographic factors. Only higher levels of antibodies against the EBNA protein in EBV was significantly linked to more relapses over time.

“Our data suggest that EBV infection is not only associated with an increased risk for MS but may also influence long-term disease progression,” the researchers wrote.

In contrast, measles and other viruses were not significantly linked to changes in disease progression in MS.

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