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- Poza-Guedes, Paloma, et al.
(author)
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Downregulation of Angiogenesis Factors, VEGF and PDGF, after Rapid IgE Desensitization and Oral Immunotherapy in Children with Food Allergy
- 2014
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In: BioMed Research International. - : Hindawi Limited. - 2314-6133 .- 2314-6141. ; 2014
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Journal article (peer-reviewed)abstract
- Background. Angiogenesis has a key role in several conditions and is regulated by several factors such as the platelet-derived growth factor (PDGF) or the vascular endothelial growth factor (VEGF). The goal of this study was to investigate the possible role of PDGF and VEGF in a group of patients with severe food allergy. Methods. We design a prospective longitudinal study (n = 30) with patients with persistent cow's milk proteins (CMP) allergy. After achieving a CMP rush desensitization protocol, a clinical followup including SPT and blood samples to determine sIgE, protein levels, PDGF, and VEGF-A and a panel of the most representative Th-1, Th-2, T-reg, and Th-17 cytokines were also monitored. Results. Baseline levels of PDGF and VEGF in the CMP allergic patients (1170 pg/mL and 253 pg/mL) were different compared to those nonallergic CMP control subjects (501 pg/mL and 108 pg/mL). Both PDGF and VEGF were significantly downregulated (P < 0.05) 6 months after completion of the CMP desensitization process and remained significantly decreased 12 months later. Conclusion. The present study shows a significant increase of PDGF and VEGF in anaphylaxis suffering children compared to a control group. Interestingly, both VEGF and PDGF were significantly downregulated after completing a full CMP rush IgE desensitization.
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| 2. |
- Van Hoecke, Annelies, et al.
(author)
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EPHA4 is a disease modifier of amyotrophic lateral sclerosis in animal models and in humans
- 2012
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In: Nature Medicine. - New York : Nature Publishing Group. - 1078-8956 .- 1546-170X. ; 18:9, s. 1418-
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Journal article (peer-reviewed)abstract
- Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting motor neurons. Disease onset and progression are variable, with survival ranging from months to decades. Factors underlying this variability may represent targets for therapeutic intervention. Here, we have screened a zebrafish model of ALS and identified Epha4, a receptor in the ephrin axonal repellent system, as a modifier of the disease phenotype in fish, rodents and humans. Genetic as well as pharmacological inhibition of Epha4 signaling rescues the mutant SOD1 phenotype in zebrafish and increases survival in mouse and rat models of ALS. Motor neurons that are most vulnerable to degeneration in ALS express higher levels of Epha4, and neuromuscular re-innervation by axotomized motor neurons is inhibited by the presence of Epha4. In humans with ALS, EPHA4 expression inversely correlates with disease onset and survival, and loss-of-function mutations in EPHA4 are associated with long survival. Furthermore, we found that knockdown of Epha4 also rescues the axonopathy induced by expression of mutant TAR DNA-binding protein 43 (TDP-43), another protein causing familial ALS, and the axonopathy induced by knockdown of survival of motor neuron 1, a model for spinomuscular atrophy. This suggests that Epha4 generically modulates the vulnerability of (motor) neurons to axonal degeneration and may represent a new target for therapeutic intervention.
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