High dose cyclophosphamide preferentially targets naïve T (CD45/CD4/RA+) cells in CIDP and MS patients

Abstract Introduction T cells occupy a central role in MS and CIDP pathogenesis. High dose cyclophosphamide's in-vivo cytotoxic-effect on circulating memory and naïve T cells is unknown. Method Three MS and five CIDP patients received cyclophosphamide (200 mg/kg) for refractory disease. Before...

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Bibliographic Details
Published in:Journal of neuroimmunology 2007-10, Vol.190 (1), p.121-126
Main Authors: Gladstone, Douglas E, Golightly, Marc G, Brannagan, Thomas H
Format: Article
Language:English
Subjects:
Adult
Allergy and Immunology
CD4 Lymphocyte Count
CD4-Positive T-Lymphocytes - drug effects
CD4-Positive T-Lymphocytes - immunology
CD4RA+
CD4RO
Chronic inflammatory demyelinating polyneuropathy
Cyclophosphamide - pharmacology
Dose-Response Relationship, Drug
Female
High dose cyclophosphamide
Humans
Immunologic Memory - drug effects
Immunologic Memory - immunology
Immunosuppressive Agents - pharmacology
Leukocyte Common Antigens - immunology
Lymphocyte Activation - drug effects
Lymphocyte Activation - immunology
Male
Middle Aged
Multiple sclerosis
Multiple Sclerosis - drug therapy
Multiple Sclerosis - immunology
Multiple Sclerosis - physiopathology
Neurology
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - drug therapy
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - immunology
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating - physiopathology
Recovery of Function - drug effects
Recovery of Function - immunology
T-Lymphocytes - drug effects
T-Lymphocytes - immunology
Treatment Outcome
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Summary:Abstract Introduction T cells occupy a central role in MS and CIDP pathogenesis. High dose cyclophosphamide's in-vivo cytotoxic-effect on circulating memory and naïve T cells is unknown. Method Three MS and five CIDP patients received cyclophosphamide (200 mg/kg) for refractory disease. Before and after chemotherapy administration, peripheral blood T-cell subsets were determined. Patients underwent serial neurologic evaluations quarterly. Results Cyclophosphamide uniformly decreased clinical disease activity. Compared to memory T cells, naïve T cells were preferentially eradicated. Discussion Cyclophosphamide effectiveness in autoimmune illness may result from Naïve T-cell destruction, as this compartment may be the source of autoreactive lymphocytes.
ISSN:0165-5728
1872-8421
DOI:10.1016/j.jneuroim.2007.07.005