Immunological and clinical consequences of treating a patient with natalizumab.

Abstract

BACKGROUND:

Long-term therapy with natalizumab increases the risk of progressive multifocal leukoencephalopathy (PML).

OBJECTIVES:

We present a patient study through therapy, the diagnosis of PML (after 29 infusions), plasma exchange (PE) and development of immune reconstitution inflammatory syndrome (IRIS).

METHODS:

Routine diagnostics, magnetic resonance imaging (MRI), immunological status (flow cytometry, T-cell migration assays and T-cell repertoire analysis), and brain biopsy with immunohistological analysis.

RESULTS:

CD49d decreased after 12 months of treatment. At PML diagnosis, CD49d expression and migratory capacity of T cells was low and peripheral T-cell receptor (TCR) complexity showed severe perturbations. The distribution of peripheral monocytes changed from CCR5+ to CCR7+. After PE some changes reverted: CD49d increased and overshot earliest levels, migratory capacities of T cells recovered and peripheral TCR complexity increased. With no clinical, routine laboratory or cerebrospinal fluid (CSF) changes, MRI 2 months after PE demonstrated progressive lesion development. Brain histopathology confirmed the presence of infiltrates indicative of IRIS without clinical signs, immunologically accompanied by CCR7/CCR5 recovery of peripheral monocytes.

CONCLUSION:

Natalizumab-associated immunological changes accompanying PML were reversible after PE; IRIS can occur very late, remain asymptomatic and be elusive to CSF analysis. Our study may provide insights into the changes under treatment with natalizumab associated with JC virus control.

• Authors: Nicholas Schwab, Karin G Höhn, Tilman Schneider-Hohendorf, Imke Metz, Max-Philipp Stenner, Samantha Jilek, Renaud A Du Pasquier, Ralf Gold, Sven G Meuth, Richard M Ransohoff, Wolfgang Brück, Heinz Wiendl
• Journal: Multiple sclerosis (Houndmills, Basingstoke, England) (Mult Scler) Vol. 18 Issue 3 Pg. 335-44 (Mar 2012) ISSN: 1477-0970 [Electronic] England
• PMID: 21908480 (Publication Type: Case Reports, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal, Humanized
• Natalizumab

Topics

• Antibodies, Monoclonal, Humanized (adverse effects, therapeutic use)
• Brain (immunology, pathology)
• Humans
• Immune Reconstitution Inflammatory Syndrome (immunology)
• JC Virus (immunology)
• Leukoencephalopathy, Progressive Multifocal (diagnosis, etiology, immunology)
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Multiple Sclerosis (complications, drug therapy, pathology)
• Natalizumab
• Plasma Exchange
• Treatment Outcome