Natalizumab treatment reduces L-selectin (CD62L) in CD4+ T cells.

Abstract

BACKGROUND:

The purpose of this research was to validate the low expression of L-selectin (CD62L) in natalizumab (NTZ)-treated patients. CD62L is involved in rolling and transmigration of leukocyte cells. A correlation between CD62LCD4+ T cells low expression and progressive multifocal leukoencephalopathy (PML) development has been suggested in multiple sclerosis (MS) patients treated with NTZ.

METHODS:

We performed a flow cytometric analysis on peripheral blood mononuclear cells (PBMC); we collected from 23 healthy donors and 225 MS patients: untreated (n = 19) or treated with NTZ (n = 113), interferon-beta (n = 26), glatiramer acetate (n = 26), fingolimod (n = 23) and rituximab (n = 18). We have also analysed two PML/IRIS (immune reconstitution inflammatory syndrome) patients and four longitudinal samples of a NTZ-treated patients before and during the development of a clinical asymptomatic magnetic resonance imaging (MRI) lesion confirmed as PML by cerebrospinal fluid (CSF) examination. Thirty-five NTZ-treated patients were studied longitudinally with three samples taken 4 months apart.

RESULTS:

The NTZ-treated patients showed a lower percentage of CD62L (33.68%, n = 113) than first-line treated patients (44.24%, n = 52, p = 0.0004). NTZ effect was already clear during the first year of treatment (34.68 ; p = 0.0184); it persisted in the following years and disappeared after drug withdrawal (44.08%). Three percent of longitudinally analysed patients showed a percentage of CD62LCD4+ T cells under a hypothetical threshold and one patient with asymptomatic PML belongs to a group which expressed low percentage of CD62LCD4+ T cells.

CONCLUSIONS:

Our research confirms that NTZ has a specific effect on CD62LCD4+ T cells consisting in decreasing of the number of positive cells. The low level of CD62L found in a clinically asymptomatic PML patient strengthens its potential usefulness as a biomarker of high PML risk in NTZ-treated patients. A larger study is required to better confirm the data.

• Authors: Michela Spadaro, Marzia Caldano, Fabiana Marnetto, Alessandra Lugaresi, Antonio Bertolotto
• Journal: Journal of neuroinflammation (J Neuroinflammation) Vol. 12 Pg. 146 (Aug 12 2015) ISSN: 1742-2094 [Electronic] England
• PMID: 26259673 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Immunologic Factors
• Natalizumab
• L-Selectin
• Rituximab
• Glatiramer Acetate
• Interferon-beta
• Fingolimod Hydrochloride

Topics

• Adult
• Aged
• CD4-Positive T-Lymphocytes (drug effects, metabolism)
• Female
• Fingolimod Hydrochloride (pharmacology)
• Glatiramer Acetate (pharmacology)
• Humans
• Immune Reconstitution Inflammatory Syndrome (cerebrospinal fluid, drug therapy, immunology)
• Immunologic Factors (pharmacology)
• Interferon-beta (pharmacology)
• L-Selectin (biosynthesis)
• Leukocyte Count
• Male
• Middle Aged
• Monocytes (drug effects)
• Multiple Sclerosis (drug therapy)
• Natalizumab (pharmacology)
• Rituximab (pharmacology)
• Young Adult