Anti-drug antibody formation in Japanese Fabry patients following enzyme replacement therapy
| Autor: | Hitoshi Sakuraba, Tomoko Shiga, Takahiro Tsukimura, Kanako Hirai, Yuya Tayama, Tadayasu Togawa |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Nonsense mutation
PBS phosphate-buffered saline Gene mutation Immunoglobulin G α-Gal α-galactosidase A Immune tolerance law.invention 03 medical and health sciences 0302 clinical medicine Endocrinology law α-Galactosidase A LC-MS/MS liquid chromatography-tandem mass spectrometry Genetics Medicine IC immunochromatographic lcsh:QH301-705.5 Molecular Biology lyso-Gb3 globotriaosylsphingosine Fabry disease lcsh:R5-920 0303 health sciences biology business.industry Anti-drug antibody 030305 genetics & heredity ELISA enzyme-linked immunosorbent assay Enzyme replacement therapy Gb3 globotriaosylceramide medicine.disease ERT enzyme replacement therapy AP alkaline phosphatase lcsh:Biology (General) Globotriaosylsphingosine Immunology biology.protein Recombinant DNA Antibody lcsh:Medicine (General) business 030217 neurology & neurosurgery Research Paper |
| Zdroj: | Molecular Genetics and Metabolism Reports, Vol 25, Iss, Pp 100650-(2020) Molecular Genetics and Metabolism Reports |
| ISSN: | 2214-4269 |
| DOI: | 10.1016/j.ymgmr.2020.100650 |
| Popis: | Enzyme replacement therapy (ERT) for Fabry disease (deficiency of α-galactosidase A, α-Gal) with recombinant α-Gals (agalsidase alfa and agalsidase beta) is widely available and improves some of the clinical manifestations and biochemical findings. However, recent reports suggest that recurrent administration of recombinant enzymes often induces the formation of anti-drug antibodies, which may have a negative impact on the outcome of the therapy. We examined the formation of anti-drug antibodies using blood samples from 97 Japanese Fabry patients following ERT and tried to characterize them by means of enzyme-linked immunosorbent assay (ELISA), serum-mediated α-Gal inhibition, and immunochromatographic (IC) assay, followed by GLA gene analysis and measurement of plasma globotriaosylsphingosine (lyso-Gb3). ELISA revealed that 20/35 (57%) classic Fabry males were antibody (Immunoglobulin G, IgG) -positive (Ab+) at 6 months after the initiation of ERT, although only two of the seventeen (12%) later-onset Fabry males and none of the 45 Fabry females were. The Ab+ state was maintained at least until 24 months after the initiation of ERT in most of the cases, the exceptions being two patients who acquired immune tolerance during ERT. As many Ab+ patients have nonsense mutations, attention should be paid to the formation of anti-drug antibodies in Fabry patients harboring such gene mutations, who hardly produce α-Gal protein. Serum-mediated α-Gal inhibition was seen in most of the Ab+ patients and the antibodies affected the reduction of the plasma lyso-Gb3 level following ERT, suggesting that the antibodies inhibit the enzyme activity. There was a correlation between the results of the IC test and those of the ELISA. As the former is easy and rapid, it should be useful as a bed-side test. Highlights • The anti-drug antibodies formed in Fabry patients during ERT were characterized. • Serum-mediated α-Gal inhibition was seen in most of the antibody-positive patients. • The immunochromatographic test is easy, rapid, and useful as a bed-side test. |
| Databáze: | OpenAIRE |
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