Immunological and pathological characterization of fatal rebound MS activity following natalizumab withdrawal. (January 2017)

• Record Type: Journal Article
• Authors: Larochelle, Catherine; Metz, Imke; Lécuyer, Marc-André; Terouz, Simone; Roger, Michel; Arbour, Nathalie; Brück, Wolfgang; Prat, Alexandre
• Is Part Of: Multiple sclerosis. Volume 23:Number 1(2017)
• Page Start: 72
• Page End: 81
• Publication Date: 2017-01
• Subjects: Multiple sclerosis -- natalizumab -- rebound -- lymphocytes -- histopathology -- flow cytometry; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/1352458516641775
• Languages: English
• ISSNs: 1352-4585

Abstract

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.