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Of the importance of the clinical phenotypes in the interpretation of the studies dealing with Fabry disease.

ABSTRACT: Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies with agalsidase alfa and beta have been available. In this letter we underline the different clinical and technical considerations the readers have to be aware of to interpret the results of studies dealing with Fabry disease and anti-agalsidase antibodies. We reaffirm that antibodies preferentially develop in the severe classic Fabry phenotype, which can mislead into interpreting that antibodies are associated with much severe clinical events.

SUBMITTER: Mauhin W

PROVIDER: S-EPMC6322341 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Of the importance of the clinical phenotypes in the interpretation of the studies dealing with Fabry disease.

Mauhin Wladimir W Lidove Olivier O Benveniste Olivier O

Orphanet journal of rare diseases 20190107 1

Fabry disease (OMIM #301500) is an X-linked disorder caused by alpha-galactosidase A deficiency with two major clinical phenotypes: classic and non-classic of different prognosis. From 2001, enzyme replacement therapies with agalsidase alfa and beta have been available. In this letter we underline the different clinical and technical considerations the readers have to be aware of to interpret the results of studies dealing with Fabry disease and anti-agalsidase antibodies. We reaffirm that antib ...[more]

PMID: 30616652

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Project description:Medical research focuses on disease-specific genes. By contrast, here we systematically examined the roles of shared genes for disease susceptibility and as therapeutic and diagnostic targets. Meta-analysis of all published disease-related genome-wide association studies (GWAS) showed that T helper (Th) cell differentiation was the most shared pathway. Expression profiling data from highly diverse CD4+ T cell-associated diseases revealed shared disease-associated genes, which were enriched for Th cell differentiation, but also metabolic and proliferative pathways. This pleiotropy suggested that altered functions of shared genes could generally increase disease susceptibility. Indeed, compared to specific genes, the shared genes were enriched for disease-associated SNPs identified by allÂ published disease-related GWAS. To examine if the shared genes induced disease-relevant pathways, we focused on transcription factors (TFs) that induced Th differentiation. Those TFs were enriched among the shared genes, as well as for disease-associated SNPs identified by GWAS, and disease-phenotypes in mice knock-out studies. Original GWAS and profiling data fromÂ patients with multiple sclerosis and allergyÂ confirmed enrichment of disease-associated SNPs in the TFs, and that the TFs were differentially expressed at early disease stages, and their targets increased in parallel with disease development. From a clinical perspective, the shared genes were significantly enriched for known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed that shared or specific genes could be used to stratify patients for individualized medicine. Our findings show that shared disease genes generally increase disease susceptibility and are important therapeutic and diagnostic targets. Patients with seasonal allergic rhinitis (SAR) show considerable variations in response to glucocorticoids (GCs) treatment. Peripheral blood mononuclear cells (PBMCs) were collected from 8 high responders (HR) and 8 low responders (LR) to GC treatment. PBMCs were challenged with diluent, grass pollen extract (ALK-AbellÃ³ A/S; 100 Î¼g/mL) as well as grass pollen extract plus glucocorticoids (100ug/mL) for one week. Total CD4+ T cells were enriched for the gene expression microarray analysis, which was performed using SurePrint G3 Human Gene Expression 8X60K microarrays.

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Of the importance of the clinical phenotypes in the interpretation of the studies dealing with Fabry disease.

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Of the importance of the clinical phenotypes in the interpretation of the studies dealing with Fabry disease.

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