Extracellular Vesicles from Human Plasma Show a Distinctive Proteome and miRNome Profile in Patients with Severe Cutaneous Adverse Reactions
Por:
Salinas-Jaramillo O., Monroy-Arreola A., Herrera-Noreña S., Guzmán-Ortiz A.L., Hernández-Hernández A., Méndez-Flores S., Domínguez-Cherit J., Duran-Figueroa N.V., Naisbitt D.J., Cortes-Reynosa P., Perez Salazar E., Quezada H., Castrejón-Flores J.L.
Publicada:
1 ene 2021
Resumen:
Cutaneous drug-induced reactions are immune-mediated responses that can lead to life-threatening diseases such as drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, and toxic epidermal necrolysis, collectively known as severe cutaneous adverse reactions (SCARs). Unfortunately, they cannot be predicted during drug development, and, at present, a prognostic biomarker is not available nor are validated in vitro assays for diagnosis. Thus, by using proteomic and microarray miRNA analysis, the cargo of extracellular vesicles obtained from SCARs patients was analyzed and correlated with the severity of the reaction. Confirmatory assays using Western blot and qRT-PCR were performed to validate findings, and bioinformatic tools were used to establish the correlation between protein and miRNAs expression between groups. The proteomic analysis showed an increase in the amount of pro-inflammatory proteins, von Willebrand factor, and C-reactive protein and a decrease in anti-inflammatory and protective proteins in the SCARs group compared with the control group. Additionally, histone protein H2A was enriched in DRESS patients. APO1 and SERPINA4 proteins, highly increased in the control group but absent in the SCARs group, are the target of several overexpressed miRNAs, suggesting that the regulation of these proteins might involve gene silencing and protein repressing mechanisms in the severe patients. According with previous reports showing its presence in plasma and T-cells, microRNA miR-18 was upregulated in extracellular vesicles obtained from the most severe patients. Determination of the unique cargo associated with different disease conditions will help to understand the pathophysiology of these complex reactions and might help to develop novel biomarkers for life-threatening iatrogenic cutaneous disease. © 2021 American Chemical Society.
Filiaciones:
Salinas-Jaramillo O.:
Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, 07340, Mexico
Monroy-Arreola A.:
Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, 07340, Mexico
Herrera-Noreña S.:
Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, 07340, Mexico
Guzmán-Ortiz A.L.:
Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, Mexico City, 06720, Mexico
Hernández-Hernández A.:
Unidad de Biología de Células Individuales (Biocelin), Laboratorio de Investigación en Patología Experimental, Hospital Infantil de México Federico Gómez, Mexico City, 06720, Mexico
Méndez-Flores S.:
Departamento de Dermatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Domínguez-Cherit J.:
Departamento de Dermatología, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, 14080, Mexico
Duran-Figueroa N.V.:
Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, 07340, Mexico
Naisbitt D.J.:
MRC Center for Drug Safety Science, University of Liverpool, Liverpool, L69 3GE, United Kingdom
Cortes-Reynosa P.:
Departamento de Biología Celular, CINVESTAV-IPN, Mexico City, 07360, Mexico
Perez Salazar E.:
Departamento de Biología Celular, CINVESTAV-IPN, Mexico City, 07360, Mexico
Quezada H.:
Laboratorio de Investigación en Inmunología y Proteómica, Hospital Infantil de México Federico Gómez, Mexico City, 06720, Mexico
Castrejón-Flores J.L.:
Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Mexico City, 07340, Mexico
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