Immunological and pathological characterization of fatal rebound MS activity following natalizumab withdrawal
C Larochelle, I Metz, MA Lécuyer… - Multiple Sclerosis …, 2017 - journals.sagepub.com
Multiple Sclerosis Journal, 2017•journals.sagepub.com
Background: Severe rebound multiple sclerosis (MS) activity is a life-threatening
complication of natalizumab (NTZ) withdrawal, for which pathogenesis and treatment are still
unclear. We report the immunological and pathological characterization of a case of central
nervous system (CNS) inflammatory demyelination after NTZ discontinuation. Objective: To
understand the pathophysiology of this neuroinflammatory condition. Methods: Antemortem
blood and cerebrospinal fluid (CSF) analysis was compared with postmortem pathological …
complication of natalizumab (NTZ) withdrawal, for which pathogenesis and treatment are still
unclear. We report the immunological and pathological characterization of a case of central
nervous system (CNS) inflammatory demyelination after NTZ discontinuation. Objective: To
understand the pathophysiology of this neuroinflammatory condition. Methods: Antemortem
blood and cerebrospinal fluid (CSF) analysis was compared with postmortem pathological …
Background
Severe rebound multiple sclerosis (MS) activity is a life-threatening complication of natalizumab (NTZ) withdrawal, for which pathogenesis and treatment are still unclear. We report the immunological and pathological characterization of a case of central nervous system (CNS) inflammatory demyelination after NTZ discontinuation.
Objective
To understand the pathophysiology of this neuroinflammatory condition.
Methods
Antemortem blood and cerebrospinal fluid (CSF) analysis was compared with postmortem pathological studies, as well as with novel flow cytometry characterization of immune cells isolated from the CNS parenchyma.
Results
Pathological analysis of the brain revealed the presence of innumerable active inflammatory demyelinating lesions typical of immunopathological pattern II. Monocytes/macrophages and B cells were enriched in the CNS parenchyma compared to the CSF. Numerous plasma cells were present in the lesions, but CD8 T lymphocytes were predominant in the parenchyma, as opposed to CD4 in the CSF. CNS-infiltrating lymphocytes expressed high levels of adhesion molecules, granzyme B (GzB), interferon-gamma (IFN-γ), and interleukin (IL)-17.
Conclusions
Our results underline the differences in immune cell populations between the CSF and the CNS parenchyma, and suggest that aggressive immunosuppressive therapy targeting both T and B lymphocytes is warranted to control the overwhelming CNS inflammation.
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