Increased CMV response at disease onset protective in long-term prognosis of Multiple Sclerosis

Immune responses against the lytic EBV antigen VCA at disease onset, played a more important prognostic role in long-term outcomes. Elevated VCA-specific immune responses, indicative for increased viral reactivation and replication, were associated with an increased risk for treatment with first-line and second-line therapies, and with shorter time to treatment onset. Unexpectedly, immune responses to another lytic antigen, EBV-EA, seemed to play a modest long-term prognostic role and were only associated with lower relapse rate during follow-up at the univariable level.

They also found that elevated immune responses against HCMV at disease onset had protective effects on a number of outcomes mostly related with disability such as the time to EDSS 4.0 and the time to develop a secondary progressive MS (SPMS) disease course. HCMV seroprevalence in patients at disease onset was 60%, HCMV establishes latency in bone marrow-derived myeloid progenitor cells and monocytes seem to be the major reservoir of HCMV persistence in peripheral blood mononuclear cells. HCMV-driven expansion of NKG2C+NK cells was associated with a lower risk of disability progression in patients with MS. Furthermore, HCMV infection was found associated with a reduced proinflammatory cytokine profile in B cells from patients with progressive MS, which may also contribute to the protective role found for this virus in MS.

Their results suggest that HCMV IgG antibody levels should be measured at the time of the first demyelinating event, insomuch as they may have protective effects on long-term disability and inflammation outcomes. Also, EBV infection was not only associated with an increased risk for MS but may also influence long-term disease prognosis.

Reference: Manuel Comabella et al; Journal of Neurology, Neurosurgery and Psychiatryhttp://dx.doi.org/10.1136/jnnp-2022-330205