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Surface plasmon resonance-based methodology for anti-adalimumab antibody identification and kinetic characterization

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Abstract

Adalimumab (ADA) is a TNF-α blocker drug antibody fully humanized and thus indistinguishable in structure and function from natural human IgG1, used in the juvenile idiopathic arthritis (JIA) treatment. Immunogenicity against the drug has been frequently detected in treated patients, and the presence of anti-ADA antibodies is correlated to treatment failure or lower clinical remission. Herein, we measured by surface plasmon resonance (SPR) both the binding and the affinity of anti-ADA antibodies to the ADA-immobilized biosensor. The binding of anti-ADA antibodies was evaluated by testing sera from ADA-treated patients (n = 30), untreated patients (n = 9), and healthy donors (n = 20) in the SPR biosensor. The optimal cut-off point was defined using the receiver operating characteristic curve (ROC-curve) analysis with 79 % (60.28 to 92.01 %, 95 % CI) sensitivity, 99 % (88.06 to 100.0 %, 95 % CI) specificity, and a positive likelihood ratio of 23. The area under the curve was 0.9298 (p < 0.0001). The apparent affinity of anti-ADA antibodies from pediatric patients’ sera was measured, analyzing the interaction of anti-drug antibodies using whole sera, enriched IgG fractions, and isolated anti-ADA antibodies. The immobilized drug ADA interacted with purified antibodies at low affinities (10−6 M > K D > 10−9 M).

Adalimumab immobilized on the biosensor chip surface detects specific anti-drug antibodies in treated patients’ sera

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Acknowledgments

We gratefully acknowledge Ente Cassa di Risparmio di Firenze for the financial support and Dr. Tadej Avcin, University of Ljubljana, Slovenia, for kindly providing positive samples.

Conflict of interest

The authors declare that they have no conflict of interest in this article.

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Authors and Affiliations

  1. Laboratory of Peptide and Protein Chemistry and Biology, Florence, Italy

    Feliciana Real-Fernández, Giada Rossi, Anna Maria Papini & Paolo Rovero

  2. Department of Neurosciences, Psychology, Drug Research and Child Health - Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy

    Feliciana Real-Fernández, Giada Rossi & Paolo Rovero

  3. Pediatric Rheumatology, AOU Meyer, Viale Gaetano Pieraccini, 24, 50141, Florence, Italy

    Rolando Cimaz, Gabriele Simonini, Teresa Giani & Ilaria Pagnini

  4. Department of Neurosciences, Psychology, Drug Research and Child Health - Sezione Età Evolutiva, University of Florence, Viale Pieraccini 24, 50139, Florence, Italy

    Rolando Cimaz & Gabriele Simonini

  5. Department of Chemistry “Ugo Schiff”, University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy

    Anna Maria Papini

Authors
  1. Feliciana Real-Fernández
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Correspondence to Paolo Rovero.

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Real-Fernández, F., Cimaz, R., Rossi, G. et al. Surface plasmon resonance-based methodology for anti-adalimumab antibody identification and kinetic characterization. Anal Bioanal Chem 407, 7477–7485 (2015). https://doi.org/10.1007/s00216-015-8915-8

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  • DOI: https://doi.org/10.1007/s00216-015-8915-8

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