Evidence map›Paper›PMID 15320898›Full record

ArticleClinical and experimental immunology2004

Methotrexate reduces antibody responses to recombinant human alpha-galactosidase A therapy in a mouse model of Fabry disease.

R D Garman, K Munroe, S M Richards

Abstract read
In one paragraph

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.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

32 citing papers in PubMed.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Review
  6. Article
  7. Review
  8. Review
  9. Rare Diseases in Glycosphingolipid Metabolism.Advances in experimental medicine and biology · 2022
    Article
  10. Article
  11. Immunogenicity of biologic agents in rheumatology.Nature reviews. Rheumatology · 2021
    Review
  12. Article
  13. Article
  14. Article
  15. Observational
  16. Article
  17. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors.

R D GarmanImmunology Laboratory, Cell and Protein Therapeutics R&D, Genzyme Corporation, Framingham, MA 01701-9322, USA. richard.garman@genzyme.com
K Munroe
S M Richards

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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.

Indexed as

alpha-GalactosidaseAnimalsAntibodiesFabry DiseaseFemaleImmunosuppressive AgentsMaleMethotrexateMiceMice, Inbred BALB CMice, KnockoutModels, AnimalRecombinant ProteinsSpleenalpha-GalactosidaseAntibodiesImmunosuppressive AgentsMethotrexateRecombinant Proteins

Identifiers

PMID15320898
PMCPMC1809149

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.