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Surface plasmon resonance-based methodology for anti-adalimumab antibody identification and kinetic characterization
- Source :
- Analytical and bioanalytical chemistry. 407(24)
- Publication Year :
- 2015
-
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). Graphical Abstract Adalimumab immobilized on the biosensor chip surface detects specific anti-drug antibodies in treated patients' sera.
- Subjects :
- Male
medicine.medical_specialty
Adolescent
Stereochemistry
Arthritis
Biochemistry
Likelihood ratios in diagnostic testing
Gastroenterology
Analytical Chemistry
Internal medicine
Adalimumab
medicine
Humans
Surface plasmon resonance
Child
Receiver operating characteristic
biology
Chemistry
Immunogenicity
Area under the curve
Surface Plasmon Resonance
medicine.disease
Kinetics
Child, Preschool
biology.protein
Female
Antibody
medicine.drug
Subjects
Details
- ISSN :
- 16182650
- Volume :
- 407
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- Analytical and bioanalytical chemistry
- Accession number :
- edsair.doi.dedup.....62a9c257fc41d042c199272de9f8dd63