B Hernández-Breijo1, M Chaparro2, D Cano-Martínez1, I Guerra3, M Iborra4, J L Cabriada5, L Bujanda6, C Taxonera7, V García-Sánchez8, I Marín-Jiménez9, M Barreiro-de Acosta10, I Vera11, M D Martín-Arranz12, F Mesonero13, L Sempere14, F Gomollón15, J Hinojosa16, J P Gisbert2, L G Guijarro17. 1. Systems Biology Department, Universidad de Alcalá and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alcalá de Henares, Spain. 2. Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IIS-IP) and CIBEREHD, Madrid, Spain. 3. Hospital de Fuenlabrada, Madrid, Spain. 4. Hospital la Fe, Valencia and CIBEREHD, Spain. 5. Hospital de Galdakano, Vizcaya, Spain. 6. Hospital de Donostia, Guipúzcoa, Instituto Biodonostia, UPV/EHU and CIBEREHD, Spain. 7. Hospital Clínico San Carlos, and IdISSC, Madrid, Spain. 8. Hospital Reina Sofía, Instituto Maimónides de Investigación Biomédica de Córdoba, Universidad de Córdoba, Córdoba, Spain. 9. Hospital Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain. 10. Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain. 11. Hospital Universitario Puerta de Hierro, Madrid, Spain. 12. Hospital Universitario la Paz, Madrid, Spain. 13. Hospital Universitario Ramón y Cajal, Madrid, Spain. 14. Hospital General de Alicante, Alicante, Spain. 15. Hospital Clínico Universitario "Lozano Blesa", IIS Aragón, Zaragoza and CIBEREHD, Spain. 16. Hospital de Manises, Valencia, Spain. 17. Systems Biology Department, Universidad de Alcalá and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Alcalá de Henares, Spain. Electronic address: luis.gonzalez@uah.es.
Abstract
BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's disease patients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CD patients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug. Copyright Â
BACKGROUND: The availability of a quantitative method to measure anti-infliximab (IFX) antibodies (ATI) would facilitate the implementation of therapeutic drug monitoring in clinical decision-making. Our aim was to standardize the homogeneous mobility shift assay (HMSA) used in the measure of ATI levels. METHODS: In this prospective longitudinal multicenter study, 50 IFX-treated Crohn's disease (CD) patients were followed up for 54weeks. During this period 360 human serum samples were analysed. Monomeric ATI levels were measured by a quantitative HMSA-method using an anti-IFX calibrator. IFX trough levels measured by ELISA were correlated with ATI levels. RESULTS: Using HMSA and a pure anti-idiotypic monoclonal antibody specific for IFX (anti-IFX calibrator), we measured the levels of monomeric ATI generated in Crohn's diseasepatients treated with IFX. Anti-IFX calibrator allowed to quantify monomeric antibodies against IFX with a low limit of quantification (3nM). The threshold level of ATI in order to classify the immunogenicity of the patients was 10nM. We observed that 24% (12/50) of IFX-treated patients developed ATI (>10nM) during the observation period (54weeks). Serum concentration of ATI higher than 10nM dramatically increased the probability (OR=51.1; 95% CI: 20.4-128.0; p<0.0001) of presenting low levels of IFX (⩽1.5nM) in serum, as observed in some CDpatients treated with standard doses of the drug. CONCLUSIONS: The HMSA-method described here allows an accurate quantification of ATI concentration in international units (IU) and therefore it could be useful in the study of the relationship between ATI concentration, infliximab level and the clinical response to the drug. Copyright Â
Authors: B Gorovits; D J Baltrukonis; I Bhattacharya; M A Birchler; D Finco; D Sikkema; M S Vincent; S Lula; L Marshall; T P Hickling Journal: Clin Exp Immunol Date: 2018-03-30 Impact factor: 4.330
Authors: María Chaparro; Adrià Aterido; Iván Guerra; Marisa Iborra; Jose Luis Cabriada; Luis Bujanda; Carlos Taxonera; Valle García-Sánchez; Ignacio Marín-Jiménez; Manuel Barreiro-de Acosta; Isabel Vera; Maria Dolores Martín-Arranz; Borja Hernández-Breijo; Francisco Mesonero; Laura Sempere; Fernando Gomollón; Joaquín Hinojosa; Fernando Bermejo; Belén Beltrán; Ainhoa Rodríguez-Pescador; Jesús María Banales; David Olivares; Patricia Aguilar-Melero; Luis Menchén; Rocío Ferreiro-Iglesias; Isabel Blazquez Gómez; Beatriz Benitez García; Luis G Guijarro; Alicia C Marin; David Bernardo; Sara Marsal; Antonio Julia; Javier P Gisbert Journal: Therap Adv Gastroenterol Date: 2019-09-25 Impact factor: 4.409
Authors: Tamara Rodríguez-Prieto; Borja Hernández-Breijo; Miguel A Ortega; Rafael Gómez; Javier Sánchez-Nieves; Luis G Guijarro Journal: Int J Mol Sci Date: 2020-11-30 Impact factor: 5.923