Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab

Research output: Contribution to journalArticle

Maria Del Pilar Martin, Petra D. Cravens, Ryan Winger, Elliot M. Frohman, Michael K. Racke, Todd N. Eagar, Scott S. Zamvil, Martin S. Weber, Bernhard Hemmer, Nitin J. Karandikar, B. K. Kleinschmidt-DeMasters, Olaf Stüve

Objective: To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS. Design: A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining. Subjects: A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy. Results: The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209 + dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4 + T cells were detectable. Conclusions: Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.

Original languageEnglish (US)
Pages (from-to)1596-1603
Number of pages8
JournalArchives of neurology
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2008

PMID: 18852339

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Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab. / Del Pilar Martin, Maria; Cravens, Petra D.; Winger, Ryan; Frohman, Elliot M.; Racke, Michael K.; Eagar, Todd N.; Zamvil, Scott S.; Weber, Martin S.; Hemmer, Bernhard; Karandikar, Nitin J.; Kleinschmidt-DeMasters, B. K.; Stüve, Olaf.

In: Archives of neurology, Vol. 65, No. 12, 01.12.2008, p. 1596-1603.

Research output: Contribution to journalArticle

Harvard

Del Pilar Martin, M, Cravens, PD, Winger, R, Frohman, EM, Racke, MK, Eagar, TN, Zamvil, SS, Weber, MS, Hemmer, B, Karandikar, NJ, Kleinschmidt-DeMasters, BK & Stüve, O 2008, 'Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab' Archives of neurology, vol. 65, no. 12, pp. 1596-1603. https://doi.org/10.1001/archneur.65.12.noc80051

APA

Del Pilar Martin, M., Cravens, P. D., Winger, R., Frohman, E. M., Racke, M. K., Eagar, T. N., ... Stüve, O. (2008). Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab. Archives of neurology, 65(12), 1596-1603. https://doi.org/10.1001/archneur.65.12.noc80051

Vancouver

Del Pilar Martin M, Cravens PD, Winger R, Frohman EM, Racke MK, Eagar TN et al. Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab. Archives of neurology. 2008 Dec 1;65(12):1596-1603. https://doi.org/10.1001/archneur.65.12.noc80051

Author

Del Pilar Martin, Maria ; Cravens, Petra D. ; Winger, Ryan ; Frohman, Elliot M. ; Racke, Michael K. ; Eagar, Todd N. ; Zamvil, Scott S. ; Weber, Martin S. ; Hemmer, Bernhard ; Karandikar, Nitin J. ; Kleinschmidt-DeMasters, B. K. ; Stüve, Olaf. / Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab. In: Archives of neurology. 2008 ; Vol. 65, No. 12. pp. 1596-1603.

BibTeX

@article{35aec1c8f22549aeb91be1adfcd3d6db,
title = "Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab",
abstract = "Objective: To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS. Design: A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining. Subjects: A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy. Results: The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209 + dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4 + T cells were detectable. Conclusions: Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.",
author = "{Del Pilar Martin}, Maria and Cravens, {Petra D.} and Ryan Winger and Frohman, {Elliot M.} and Racke, {Michael K.} and Eagar, {Todd N.} and Zamvil, {Scott S.} and Weber, {Martin S.} and Bernhard Hemmer and Karandikar, {Nitin J.} and Kleinschmidt-DeMasters, {B. K.} and Olaf St{\"u}ve",
year = "2008",
month = "12",
day = "1",
doi = "10.1001/archneur.65.12.noc80051",
language = "English (US)",
volume = "65",
pages = "1596--1603",
journal = "Archives of Neurology",
issn = "0003-9942",
publisher = "American Medical Association",
number = "12",

}

RIS

TY - JOUR

T1 - Decrease in the numbers of dendritic cells and CD4 + T cells in cerebral perivascular spaces due to natalizumab

AU - Del Pilar Martin, Maria

AU - Cravens, Petra D.

AU - Winger, Ryan

AU - Frohman, Elliot M.

AU - Racke, Michael K.

AU - Eagar, Todd N.

AU - Zamvil, Scott S.

AU - Weber, Martin S.

AU - Hemmer, Bernhard

AU - Karandikar, Nitin J.

AU - Kleinschmidt-DeMasters, B. K.

AU - Stüve, Olaf

PY - 2008/12/1

Y1 - 2008/12/1

N2 - Objective: To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS. Design: A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining. Subjects: A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy. Results: The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209 + dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4 + T cells were detectable. Conclusions: Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.

AB - Objective: To extend our studies on the prolonged and differential effect of natalizumab on T lymphocyte numbers in the cerebrospinal fluid, we investigated the number and phenotypes of leukocytes and the expression of major histocompatibility complex (MHC) classes I and II in cerebral perivascular spaces (CPVS). We hypothesized that natalizumab reduces the number of antigen presenting cells in CPVS. Design: A case-control study in which inflammatory cell numbers in the CPVS of cerebral tissue were assessed by immunohistochemical staining. Subjects: A patient with multiple sclerosis (MS) who developed progressive multifocal leukoencephalopathy (PML) during natalizumab therapy. Controls included location-matched cerebral autopsy material of patients without disease of the central nervous system, patients with MS not treated with natalizumab, and patients with PML not associated with natalizumab therapy. Results: The absolute number of CPVS in the patient with MS treated with natalizumab was significantly lower than in the control groups owing to extensive destruction of the tissue architecture. The expression of MHC class II molecules and the number of CD209 + dendritic cells were significantly decreased in the CPVS of the patient with MS treated with natalizumab. No CD4 + T cells were detectable. Conclusions: Our observations may explain the differential and prolonged effects of natalizumab therapy on leukocyte numbers in the cerebrospinal fluid.

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U2 - 10.1001/archneur.65.12.noc80051

DO - 10.1001/archneur.65.12.noc80051

M3 - Article

VL - 65

SP - 1596

EP - 1603

JO - Archives of Neurology

T2 - Archives of Neurology

JF - Archives of Neurology

SN - 0003-9942

IS - 12

ER -

ID: 16808504