binding antibodies predict neutralizing antibody development
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.
Multiple Sclerosis, 2014, Vol 20, Issue 5, p. 577-587
Adult; Antibodies, Neutralizing; Biological Markers; Chemokine CXCL10; Demyelinating Diseases; Early Diagnosis; Europe; Female; Humans; Immunologic Factors; Interferon-beta; Male; Middle Aged; Multiple Sclerosis, Relapsing-Remitting; Myxovirus Resistance Proteins; Predictive Value of Tests; Prospective Studies; TNF-Related Apoptosis-Inducing Ligand; Time Factors; Treatment Outcome; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't