Author Topic: (Abst.) Fatal rebound MS activity after Tysabri withdrawal...  (Read 19 times)

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Offline agate

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From PubMed, April 3, 2016:

Quote
Mult Scler. 2016 Apr 1.

Immunological and pathological characterization of fatal rebound MS activity following natalizumab withdrawal

Larochelle C1, Metz I2, Lécuyer MA3, Terouz S3, Roger M4, Arbour N5, Brück W2, Prat A6.

Author information

1Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada/Multiple Sclerosis Clinic, Division of Neurology, CHUM-Notre-Dame Hospital, Montréal, QC, Canada/Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.

2Department of Neuropathology, Faculty of Medicine, Universitätsmedizin Göttingen, Göttingen, Germany.

3Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada.

4Department of Microbiology and Immunology, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.

5Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada/Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada.

6Neuroimmunology Research Laboratory, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montréal, QC, Canada/Multiple Sclerosis Clinic, Division of Neurology, CHUM-Notre-Dame Hospital, Montréal, QC, Canada/Department of Neurosciences, Faculty of Medicine, Université de Montréal, Montréal, QC, Canada a.prat@umontreal.ca.

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.

The abstract can be seen here.





SPMS, diagnosed 1980. Avonex 2001-2004. Copaxone 2007-2010.

 

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