Abstract

Immune response to biologics treatment, while widely reported, yet fails to correlate with clinical outcomes and assay to assay comparison is often not possible. Hence, we developed a new peptide based-detection assay to stratify pediatric patients with juvenile idiopathic arthritis (JIA) or chronic non-infectious uveitis (CNU) and monitor anti-drug antibodies (ADAbs) formed as part of an immune response to treatment with the fully human monoclonal therapeutic antibody Adalimumab. Adalimumab derived synthetic peptides were optimized for maximum immunogenicity and were tested by SP-ELISA on a development cohort of 18 JIA and CNU treated patients. The two best performing peptides able to differentiate patient groups were selected for evaluation with a larger scale ELISA testing on a total of 29 sera from pediatric patients with JIA or CNU. The results of this peptide-based assay were compared to an in-house developed SPR biosensor ADAbs assay and a commercially available bridging ELISA. The first peptide, termed HC3, was able to positively detect ADAbs in 7 out of the 29 sera, while the second peptide, called LC3, was able to detect ADAbs in 11 out of 29 sera in the evaluation group. Following statistical data evaluation, it has been found that the detection of ADAbs using the peptide-based ELISA assay positively correlates with disease progression and remission. Two synthetic peptides derived from Adalimumab may provide a beneficial tool to clinicians for monitoring patient response to such treatment and taking informed decisions for treatment alternatives.

Details

Title
A peptide-based anti-Adalimumab antibody assay to monitor immune response to biologics treatment in juvenile idiopathic arthritis and childhood chronic non-infectious uveitis
Author
Rusche Hendrik 1 ; Marrani Edoardo 2 ; Real-Fernandez, Feliciana 3 ; Ponti, Roberta 4 ; Terzani Francesco 5 ; Maccora Ilaria 2 ; Monasson Olivier 6 ; Mastrolia, Maria Vincenza 2 ; Peroni, Elisa 6 ; Pagnini Ilaria 2 ; Cimaz Rolando 7 ; Papini, Anna Maria 8 ; Simonini Gabriele 9 ; Rovero Paolo 3 

 CY Cergy Paris Université, Peptlab@UCP Platform of Peptide and Protein Chemistry and Biology and UMR 8076 CNRS-BioCIS, CNRS, Neuville sur Oise, France (GRID:grid.507676.5); Fischer analytics GmbH, Weiler, Germany (GRID:grid.507676.5) 
 AOU Meyer, Pediatric Rheumatology Unit, Florence, Italy (GRID:grid.413181.e) (ISNI:0000 0004 1757 8562) 
 University of Florence, Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, Sesto Fiorentino, Italy (GRID:grid.8404.8) (ISNI:0000 0004 1757 2304) 
 University Hospital of Udine, Department of Medicine, Udine, Italy (GRID:grid.411492.b) 
 CY Cergy Paris Université, Peptlab@UCP Platform of Peptide and Protein Chemistry and Biology and UMR 8076 CNRS-BioCIS, CNRS, Neuville sur Oise, France (GRID:grid.507676.5); University of Florence, Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Department of NeuroFarBa, Sesto Fiorentino, Italy (GRID:grid.8404.8) (ISNI:0000 0004 1757 2304) 
 CY Cergy Paris Université, Peptlab@UCP Platform of Peptide and Protein Chemistry and Biology and UMR 8076 CNRS-BioCIS, CNRS, Neuville sur Oise, France (GRID:grid.507676.5) 
 University of Milano, Department of Clinical Sciences and Community Health, Milan, Italy (GRID:grid.4708.b) (ISNI:0000 0004 1757 2822) 
 CY Cergy Paris Université, Peptlab@UCP Platform of Peptide and Protein Chemistry and Biology and UMR 8076 CNRS-BioCIS, CNRS, Neuville sur Oise, France (GRID:grid.507676.5); University of Florence, Interdepartmental Laboratory of Peptide and Protein Chemistry and Biology, Department of Chemistry “Ugo Schiff”, Sesto Fiorentino, Italy (GRID:grid.8404.8) (ISNI:0000 0004 1757 2304) 
 AOU Meyer, Pediatric Rheumatology Unit, Florence, Italy (GRID:grid.413181.e) (ISNI:0000 0004 1757 8562); University of Florence, Department of NeuroFarBa, Florence, Italy (GRID:grid.8404.8) (ISNI:0000 0004 1757 2304) 
Publication year
2021
Publication date
2021
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2560480536
Copyright
© The Author(s) 2021. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.