ArticleClinical and experimental immunology2004
Methotrexate reduces antibody responses to recombinant human alpha-galactosidase A therapy in a mouse model of Fabry disease.
Article in Clinical and experimental immunology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- Cross-reactive immunologic material status affects treatment outcomes in Pompe disease infants.Molecular genetics and metabolism · 2010Trial
- Immunogenicity in Fabry Disease: Current Issues, Coping Strategies, and Future Directions.Biomedicines · 2026Review
- A Fulminant Case of Refractory Sarcoidosis Triggered by Infliximab-Neutralizing Antibodies.Cureus · 2025Article
- Enzyme Replacement and Immunosuppression in Heart Transplant Recipients with Fabry Cardiomyopathy: A 7-Year Case Study.The American journal of case reports · 2025Article
- Advances in Immune Tolerance Induction in Enzyme Replacement Therapy.Paediatric drugs · 2024Review
- Conversion of Chemical Drugs into Targeting Ligands on RNA Nanoparticles and Assessing Payload Stoichiometry for Optimal Biodistribution in Cancer Treatment.RNA nanomed · 2024Article
- The Role of Low-Dose Oral Methotrexate in Increasing Anti-TNF Drug Levels and Reducing Immunogenicity in IBD.Journal of clinical medicine · 2023Review
- Oral tolerance to prevent anti-drug antibody formation in protein replacement therapies.Cellular immunology · 2022Review
- Rare Diseases in Glycosphingolipid Metabolism.Advances in experimental medicine and biology · 2022Article
- Expansion of immature, nucleated red blood cells by transient low-dose methotrexate immune tolerance induction in mice.Clinical and experimental immunology · 2021Article
- Immunogenicity of biologic agents in rheumatology.Nature reviews. Rheumatology · 2021Review
- Anti-drug antibody formation in Japanese Fabry patients following enzyme replacement therapy.Molecular genetics and metabolism reports · 2020Article
- Therapeutic challenges in two adolescent male patients with Fabry disease and high antibody titres.Molecular genetics and metabolism reports · 2020Article
- Antidrug antibody formation during tumor necrosis factor α inhibitor treatment of severe psoriatic patients in the real-life practice.Postepy dermatologii i alergologii · 2019Article
- Higher Mucosal Healing with Tumor Necrosis Factor Inhibitors in Combination with Thiopurines Compared to Methotrexate in Crohn's Disease.Digestive diseases and sciences · 2019Observational
- Systemic mRNA Therapy for the Treatment of Fabry Disease: Preclinical Studies in Wild-Type Mice, Fabry Mouse Model, and Wild-Type Non-human Primates.American journal of human genetics · 2019Article
- An immune tolerance approach using transient low-dose methotrexate in the ERT-naïve setting of patients treated with a therapeutic protein: experience in infantile-onset Pompe disease.Genetics in medicine : official journal of the American College of Medical Genetics · 2019Article
- Effects of Enzyme Replacement Therapy and Antidrug Antibodies in Patients with Fabry Disease.Journal of the American Society of Nephrology : JASN · 2018Review
- Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development.The AAPS journal · 2017Review
- Antidrug Antibody Formation in Oncology: Clinical Relevance and Challenges.The oncologist · 2016Review
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Therapeutic enzymes are often recognized as foreign by the immune system of patients undergoing enzyme replacement therapy. The antibodies that develop may alter pharmacokinetics and biodistribution of the therapeutic protein, may be able to neutralize the activity of the enzyme, or may cause immune reactions in certain patients. We have explored treatment regimens to reduce the antibody response to human alpha-galactosidase A (r-halphaGAL) in Fabry (alphaGAL knock-out) and normal BALB/c mice. A wide variety of treatment modalities were tested, including high dose tolerance induction, increased frequency of therapeutic doses and immunosuppressive drugs in combination with administration of enzyme. The most substantial effects were observed in mice injected intravenously with r-halphaGAL in combination with methotrexate (MTX), which significantly lowered r-halphaGAL-specific serum antibody levels. A short course of treatment with MTX was able to reduce antibody and spleen cell proliferative responses to long-term r-halphaGAL treatment. MTX was able to suppress the development of r-halphaGAL-specific IgG in antigen-primed mice. However, MTX was not effective in dampening robust ongoing antibody responses. These experiments provide a framework for the design of clinical protocols to prevent the drug-specific antibody responses of patients undergoing enzyme replacement therapy.
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