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Is MS a complication of virus infection?

Epstein–Barr virus (EBV) is a ubiquitous human herpesvirus that has the ability to infect, activate, and clonally expand B lymphocytes, and then persist as a latent infection within these cells.1 At ECTRIMS, we heard how a team from the Medical University of Berlin applied a step-wise approach to detect EBV antibodies in 901 samples from untreated patients with CIS or RRMS collected for the German National MS cohort.2 They found 100% of the patients with CIS or MS were seropositive for EBV, strengthening the proposal that MS is a rare complication of EBV infection. The authors proposed that if a patient diagnosed with MS is seronegative for EBV, an alternative diagnosis should be considered.2

Another interesting study presented at ECTRIMS revealed an insight into how EBV infection might contribute to the development of MS: the investigators assessed IgG antibody reactivity to the calcium-activated chloride channel protein, anoctamin 2 (ANO2), and the EBV nuclear antigen 1 (EBNA1), in 8753 MS cases and 7230 controls.3 Patients with MS had increased ANO2 antibody levels compared with controls, but no increase in ANO2-seropositivity was observed in patients with three other inflammatory diseases (idiopathic inflammatory myopathy, systemic lupus erythematosus and rheumatoid arthritis). Reciprocal blocking experiments with ANO2 and EBNA1 fragments showed cross-reactivity between the two proteins, suggesting that EBNA1 may mimic ANO2, leading to T-cell reactivity to ANO2 that contributes to the pathogenesis of MS.3

 

Neurofilament light protein: is it ready for prime time?

In recent years, there has been much excitement surrounding serum neurofilament light chain (sNfL), a blood biomarker that reflects acute and chronic neural damage.7 Is there now sufficient evidence supporting its use to begin using it in clinical practice?

Peter Calabresi (John Hopkins Hospital, Baltimore, USA) presented a study evaluating levels of sNfL in samples from more than 1400 patients with RRMS across four Phase III clinical studies.8 Consistently low levels of sNfL were observed in patients with no evident disease activity; elevated levels were seen in patients with active disease, particularly in those with high rates of brain atrophy. sNfL levels above 16 pg/mL indicated a high probability of disease activity over the following year, and, in the long-term, were associated with worse clinical and MRI imaging outcomes than in patients with levels below 16 pg/mL. Treatment with a DMT was also associated with significantly lower sNFL levels.8

In a separate, observational study conducted in Sweden, sNfL levels were taken from 1362 patients with RRMS at the start of treatment with different DMTs.9 Age-adjusted NfL values at baseline were significantly associated with the number of previous relapses; the change in NfL from baseline to 12 months depended mostly on baseline NfL level, followed by the type of DMT received, whether a patient was naive to DMT at baseline, the change in Multiple Sclerosis Severity Score (MSSS) and the change in the Psychological domain of the Multiple Sclerosis Impact Score (MSIS-29) During treatment, there were significant differences in NfL levels between the DMTs.9

These results support the use of NfL in monitoring treatment effects in RRMS. Establishing a standardised, robust and widely accessible assay, as well as validating sNfL in prospective and real-world cohorts, are the essential next steps for implementation of sNfL into clinical practice.8

References

  1. Pender MP and Burrows SR. Epstein-Barr virus and multiple sclerosis: potential opportunities for immunotherapy. Clin Transl Immunology. 2014 Oct 31;3(10):e27. 

  2. Abrahamyan S et al. Absence of Epstein-Barr virus seronegativity in a large cohort of patients with early multiple sclerosis (320). Oral presentation at ECTRIMS 2018, 12 Oct 2018, Berlin, Germany. 

  3. Olsson T. Molecular mimicry between the autoantigen Anoctamin 2 and Epstein Barr virus nuclear antigen 1 associates with increased risk for multiple sclerosis (167). Oral presentation at ECTRIMS 2018, 11 Oct 2018, Berlin, Germany. 

  4. Giovannoni G et al. Brain health: time matters in multiple sclerosis. Mult Scler Relat Disord 2016; 9 Suppl 1: S5–S48. 

  5. Jick S. Increased risk of comorbidities in patients before as well as after multiple sclerosis (MS) diagnosis: a study in the UK Clinical Practice Research Datalink (CPRD; 146). Oral presentation at ECTRIMS 2018, 11 Oct 2018, Berlin, Germany. 

  6. Crous-Bou M et al. Environmental and genetic risk factors associated with venous thromboembolism Semin Thromb Hemost. 2016; 42(8): 808–820. 

  7. Siller N et al. Mult Scler. Serum neurofilament light chain is a biomarker of acute and chronic neuronal damage in early multiple sclerosis. 2018 Mar 1:1352458518765666. 

  8. Calabresi P. Serum neurofilament light (NfL) for disease prognosis and treatment monitoring in multiple sclerosis patients: is it ready for implementation into clinical care? (158). Oral presentation at ECTRIMS 2018, 11 Oct 2018, Berlin, Germany.

  9. Delcoigne B. Plasma neurofilament light levels segregate treatment effects: results from the IMSE studies with multiple disease modulatory drugs (205). Oral presentation at ECTRIMS 2018, 11 Oct 2018, Berlin, Germany.