Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients : binding antibodies predict neutralizing antibody development. / 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, C H; Rudzki, D; Schautzer, F; Sellebjerg, F; Sørensen, P S; Deisenhammer, F.
I: Multiple Sclerosis, Bind 20, Nr. 5, 04.2014, s. 577-587.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients
T2 - binding antibodies predict neutralizing antibody development
AU - Hegen, H
AU - Millonig, A
AU - Bertolotto, A
AU - Comabella, M
AU - Giovanonni, G
AU - Guger, M
AU - Hoelzl, M
AU - Khalil, M
AU - Killestein, J
AU - Lindberg, R
AU - Malucchi, S
AU - Mehling, M
AU - Montalban, X
AU - Polman, C H
AU - Rudzki, D
AU - Schautzer, F
AU - Sellebjerg, F
AU - Sørensen, P S
AU - Deisenhammer, F
PY - 2014/4
Y1 - 2014/4
N2 - BACKGROUND: 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.OBJECTIVES: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution.METHODS: 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.RESULTS: 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.CONCLUSIONS: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.
AB - BACKGROUND: 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.OBJECTIVES: To investigate whether early binding antibody (BAb) titers or different IFN-b biomarkers predict NAb evolution.METHODS: 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.RESULTS: 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.CONCLUSIONS: BAb titers reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.
KW - Adult
KW - Antibodies, Neutralizing
KW - Biological Markers
KW - Chemokine CXCL10
KW - Demyelinating Diseases
KW - Early Diagnosis
KW - Europe
KW - Female
KW - Humans
KW - Immunologic Factors
KW - Interferon-beta
KW - Male
KW - Middle Aged
KW - Multiple Sclerosis, Relapsing-Remitting
KW - Myxovirus Resistance Proteins
KW - Predictive Value of Tests
KW - Prospective Studies
KW - TNF-Related Apoptosis-Inducing Ligand
KW - Time Factors
KW - Treatment Outcome
U2 - 10.1177/1352458513503597
DO - 10.1177/1352458513503597
M3 - Journal article
C2 - 24009164
VL - 20
SP - 577
EP - 587
JO - Multiple Sclerosis Journal
JF - Multiple Sclerosis Journal
SN - 1352-4585
IS - 5
ER -
ID: 138545599