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Qualitative and quantitative analysis of antibody response against IFNß in patients with multiple sclerosis

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy, neurobiologia{at}sanluigi.piemonte.it

F Hoffmann

Department of Research, University Hospitals Basel, Basel, Switzerland

A Sala

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

F Marnetto

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

M Caldano

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

P Valentino

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

L Kappos

Department of Neurology, University Hospitals Basel, Basel, Switzerland

A Bertolotto

Centro di Riferimento Regionale Sclerosi Multipla (CReSM) and Neurobiologia Clinica, ASO S. Luigi Gonzaga, Orbassano, Torino, Italy

R LP Lindberg

Department of Research, University Hospitals Basel, Basel, Switzerland

To date, inter-and intra-laboratory consistency of binding assays for measuring anti-interferon (IFN)ß antibodies has not been assessed. In this investigation, two independent laboratories tested a library of 80 serum specimens obtained from multiple sclerosis (MS) patients treated with IFNß. For binding antibodies (BAbs) evaluations, each laboratory used both a capture-ELISA (cELISA) and an enzyme-immuno-assay (EIA), which is commercially available. Samples were also tested for neutralizing antibodies (NAbs). Data demonstrated good intra-laboratory reliability (r_pearson0.86), and a good overall agreement between the results obtained from the two centers, using both the cELISA (69/80 of observed agreements) and the EIA (67/80). Accordingly, kappa coefficients (K) showed good concurrence (K 0.651). There was also substantial agreement between cELISA and EIA measurements, as performed in both centers (Orbassano, 66/80, K = 0.631; Basel, 70/80, K = 0.717). However, by comparing NAbs and BAbs titers obtained with both assays, we found that a high degree of BAb-negative samples were positive in NAb-assay. Thus, our study does not support the usefulness of ELISA-based BAb assays as a screening tool for NAbs. Otherwise, BAb-assays can be used as a confirmation test, indicating that the decrease of the biological effects is due to antibodies. In this context, both ELISA-based assays are equally reliable techniques.

Key Words: binding antibodies • ELISA • IFNß • multiple sclerosis • neutralizing antibodies

Multiple Sclerosis, Vol. 12, No. 6, 738-746 (2006)
DOI: 10.1177/1352458506070968


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