Accepted for/Published in: JMIR Bioinformatics and Biotechnology
Date Submitted: Sep 9, 2025
Open Peer Review Period: Sep 9, 2025 - Sep 24, 2025
Date Accepted: Nov 14, 2025
(closed for review but you can still tweet)
In Silico Analysis of Bacterial Molecular Mimicry to Explain Immunogenicity of Adalimumab
ABSTRACT
Background:
Adalimumab, a monoclonal antibody targeting TNFα, treats autoimmune diseases but induces anti-drug antibodies in 30–60% of patients, reducing its efficacy.
Objective:
This study investigates molecular mimicry as a mechanism behind this immunogenicity, where bacterial immunoglobulin domains structurally resemble adalimumab’s light chain, triggering immune responses.
Methods:
Using PSI-BLASTp and IBIVU Praline, there are 40 bacterial antigens homologous to adalimumab, with eight clinically relevant strains.
Results:
Structural analysis revealed 94% amino acid identity between the immunoglobulin domain of Escherichia coli strain B1 and adalimumab’s light chain, and 89.67% similarity with Corynebacterium pyruviciproducens. Root Mean Square Deviation values confirmed strong structural homology. Additionally, five cross-reactive B-cell epitopes were predicted, suggesting overlapping surfaces that may promote immune cross-reactivity and anti-drug antibody development.
Conclusions:
These findings emphasize the role of bacterial immunoglobulin domains in adalimumab immunogenicity and highlight further need for experimental validation and improved strategies to reduce immune responses in biological therapies.
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Copyright
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