L-selectin is a possible biomarker for individual PML risk in natalizumab-treated MS patients.
OBJECTIVE
To find biomarkers identifying patients at risk for the development of progressive multifocal leukoencephalopathy (PML) during natalizumab treatment.


METHODS
Patients were recruited from 10 European and US cohorts. Of 289 patients with multiple sclerosis (MS), 224 had been treated with natalizumab (18-80 months), 21 received other immune-modulatory treatments, and 28 were untreated. We had access to samples from 16 natalizumab PML patients. Eight of these patients had given blood before the diagnosis of PML. We also analyzed non-natalizumab-treated patients who developed PML (n = 10) and age- and sex-matched healthy donors (n = 31). All flow cytometric assessments were done on previously cryopreserved, viable peripheral blood mononuclear cells.


RESULTS
The percentage of l-selectin-expressing CD4+ T cells was significantly lower in patients treated long-term with natalizumab (40.2%) when compared with patients not receiving natalizumab treatment (47.2%; p = 0.016) or healthy controls (61.0%; p < 0.0001). An unusually low percentage (9-fold lower; 4.6%) was highly correlated with the risk of developing PML in the patient group with available pre-PML samples when compared with non-PML natalizumab-treated patients (p ≤ 0.0001). Samples were gathered between 4 and 26 months before PML diagnosis.


CONCLUSIONS
The cell-based assessment of the percentage of l-selectin-expressing CD4 T cells could provide an urgently needed biomarker for individual PML risk assessment.
Department of Neurology, University of Münster, Germany.
Nicholas
N
Schwab
Tilman
T
Schneider-Hohendorf
Vilmos
V
Posevitz
Johanna
J
Breuer
Kerstin
K
Göbel
Susanne
S
Windhagen
Bruno
B
Brochet
Patrick
P
Vermersch
Christine
C
Lebrun-Frenay
Anita
A
Posevitz-Fejfár
Ruggero
R
Capra
Luisa
L
Imberti
Vera
V
Straeten
Juergen
J
Haas
Brigitte
B
Wildemann
Joachim
J
Havla
Tania
T
Kümpfel
Ingrid
I
Meinl
Kyle
K
Niessen
Susan
S
Goelz
Christoph
C
Kleinschnitz
Clemens
C
Warnke
Dorothea
D
Buck
Ralf
R
Gold
Bernd C
BC
Kieseier
Sven G
SG
Meuth
John
J
Foley
Andrew
A
Chan
David
D
Brassat
Heinz
H
Wiendl
D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D006801:Humans; D019041:L-Selectin / Q000097:blood*; D007968:Leukoencephalopathy, Progressive Multifocal / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D009103:Multiple Sclerosis / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D000069442:Natalizumab; D012307:Risk Factors; D016896:Treatment Outcome
D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; D000069442:Natalizumab; D019041:L-Selectin