| Autor: |
Schwab, Nicholas, Höhn, Karin G, Schneider-Hohendorf, Tilman, Metz, Imke, Stenner, Max-Philipp, Jilek, Samantha, Du Pasquier, Renaud A, Gold, Ralf, Meuth, Sven G, Ransohoff, Richard M, Brück, Wolfgang, Wiendl, Heinz |
| Předmět: |
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| Zdroj: |
Multiple Sclerosis Journal; Mar2012, Vol. 18 Issue 3, p335-344, 10p, 1 Color Photograph, 1 Diagram, 1 Chart, 3 Graphs |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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