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SHR Neuro Krebs Kardio Lipid Stoffw Microb

Hegen, H; Millonig, A; Bertolotto, A; Comabella, M; Giovanonni, G; Guger, M; Hoelzl, M; Khalil, M; Killestein, J; Lindberg, R; Malucchi, S; Mehling, M; Montalban, X; Polman, CH; Rudzki, D; Schautzer, F; Sellebjerg, F; Sørensen, PS; Deisenhammer, F.
Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development.
Mult Scler. 2014; 20(5):577-587 Doi: 10.1177/1352458513503597
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Co-Autor*innen der Med Uni Graz
Khalil Michael

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Neutralizing antibodies (NAb) affect efficacy of interferon-beta (IFN-b) treatment in multiple sclerosis (MS) patients. NAbs evolve in up to 44% of treated patients, usually between 6-18 months on therapy. To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution. We included patients with MS or clinically isolated syndrome (CIS) receiving de novo IFN-b treatment in this prospective European multicenter study. Blood samples were collected at baseline, before and after the first IFN-b administration, and again after 3, 12 and 24 months on that therapy; for determination of NAbs, BAbs, gene expression of MxA and protein concentrations of MMP-9, TIMP-1, sTRAIL, CXCL-10 and CCL-2. We found that 22 of 164 (13.4%) patients developed NAbs during a median time of 23.8 months on IFN-b treatment. Of these patients, 78.9% were BAb-positive after 3 months. BAb titers ≥ 1:2400 predicted NAb evolution with a sensitivity of 74.7% and a specificity of 98.5%. Cross-sectionally, MxA levels were significantly diminished in the BAb/NAb-positive samples; similarly, CXCL-10 and sTRAIL concentrations in BAb/NAb-positive and BAb-positive/NAb-negative samples, respectively, were also diminished compared to BAb/NAb-negative samples. BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.
Find related publications in this database (using NLM MeSH Indexing)
Adult -
Antibodies, Neutralizing - blood
Biomarkers - blood
Chemokine CXCL10 - blood
Demyelinating Diseases - blood
Demyelinating Diseases - diagnosis
Demyelinating Diseases - drug therapy
Demyelinating Diseases - immunology
Early Diagnosis -
Early Diagnosis -
Female -
Humans -
Immunologic Factors - immunology
Immunologic Factors - therapeutic use
Interferon-beta - immunology
Interferon-beta - therapeutic use
Male -
Middle Aged -
Multiple Sclerosis, Relapsing-Remitting - blood
Multiple Sclerosis, Relapsing-Remitting - diagnosis
Multiple Sclerosis, Relapsing-Remitting - drug therapy
Multiple Sclerosis, Relapsing-Remitting - genetics
Multiple Sclerosis, Relapsing-Remitting - immunology
Myxovirus Resistance Proteins - genetics
Predictive Value of Tests -
Prospective Studies -
TNF-Related Apoptosis-Inducing Ligand - blood
Time Factors -
Treatment Outcome -

Find related publications in this database (Keywords)
neutralizing antibody
multiple sclerosis
Binding antibody
clinically-isolated syndrome
drug resistance
multicenter study
myxovirus protein A
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