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Lipid‐specific immunoglobulin M bands in cerebrospinal fluid are associated with a reduced risk of developing progressive multifocal leukoencephalopathy during treatment with natalizumab
Author(s) -
Villar Luisa M.,
CostaFrossard Lucienne,
Masterman Thomas,
Fernandez Oscar,
Montalban Xavier,
Casanova Bonaventura,
Izquierdo Guillermo,
Coret Francisco,
Tumani Hayrettin,
Saiz Albert,
Arroyo Rafael,
Fink Katharina,
Leyva Laura,
Espejo Carmen,
SimóCastelló María,
GarcíaSánchez María I.,
Lauda Florian,
Llufriú Sara,
ÁlvarezLafuente Roberto,
Olascoaga Javier,
Prada Alvaro,
Oterino Agustín,
de Andrés Clara,
Tintoré Mar,
RamióTorrentà Lluis,
RodríguezMartín Eulalia,
Picón Carmen,
Comabella Manuel,
Quintana Ester,
Agüera Eduardo,
Díaz Santiago,
FernandezBolaños Ricardo,
GarcíaMerino Juan A.,
Landete Lamberto,
MenéndezGonzález Manuel,
Navarro Laura,
Pérez Domingo,
SánchezLópez Fernando,
SerranoCastro Pedro J.,
Tuñón Alberto,
Espiño Mercedes,
Muriel Alfonso,
BarOr Amit,
ÁlvarezCermeño José C.
Publication year - 2015
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.24345
Subject(s) - natalizumab , progressive multifocal leukoencephalopathy , multiple sclerosis , cerebrospinal fluid , medicine , odds ratio , antibody , gastroenterology , immunology , opportunistic infection , jc virus , confidence interval , viral disease , virus
Objective Progressive multifocal leukoencephalopathy (PML) is a serious side effect associated with natalizumab treatment in multiple sclerosis (MS). PML risk increases in individuals seropositive for anti–John Cunningham virus (JC) antibodies, with prolonged duration of natalizumab treatment, and with prior exposure to immunosuppressants. We explored whether the presence of lipid‐specific immunoglobulin M oligoclonal bands in cerebrospinal fluid (CSF; IgM bands), a recognized marker of highly inflammatory MS, may identify individuals better able to counteract the potential immunosuppressive effect of natalizumab and hence be associated with a reduced risk of developing PML. Methods We studied 24 MS patients who developed PML and another 343 who did not suffer this opportunistic infection during natalizumab treatment. Patients were recruited at 25 university hospitals. IgM bands were studied by isoelectric focusing and immunodetection. CSF lymphocyte counts were explored in 151 MS patients recruited at Ramon y Cajal Hospital in Madrid, Spain. Results IgM bands were independently associated with decreased PML risk (odds ratio [OR] = 45.9, 95% confidence interval [CI] = 5.9–339.3, p < 0.0001) in patients treated with natalizumab. They were also associated with significantly higher CSF CD4, CD8, and B‐cell numbers. Patients positive for IgM bands and anti‐JC antibodies had similar levels of reduced PML risk to those who were anti‐JC negative (OR = 1.55, 95% CI = 0.09–25.2, p = 1.0). Higher risk was observed in patients positive for anti‐JC antibodies and negative for IgM bands (19% of the total cohort, OR = 59.71, 95% CI = 13.6–262.2). Interpretation The presence of IgM bands reflects a process that may diminish the risk of PML by counteracting the excess of immunosuppression that may occur during natalizumab therapy. Ann Neurol 2015;77:447–457