Wednesday, 11 September 2013

BABS predict NABS...Stopping interferons working

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, Rudzki D, Schautzer F, Sellebjerg F, Sørensen P, Deisenhammer F. Early detection of neutralizing antibodies to interferon-beta in multiple sclerosis patients: binding antibodies predict neutralizing antibody development.Mult Scler. 2013 Sep 5. [Epub ahead of print]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) titres 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 interferon-induced MxA transcription protein 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 titres ≥ 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 titres reliably predict NAbs. CXCL-10 is a promising sensitive biomarker for IFN-b response and its abrogation by anti-IFN-b antibodies.

Now change HIV for beta interferon

A neutralising antibody binds to the active site and stops it working, a binding antibody binds to any bit of the molecule. That BAbs predict NABS is hardly surprising as a NAb is a subset of a Bab. This studies indicates the more antibodies you produce the more likely you will produce Neutralising antibodies.

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