RESUMEN
Serum and plasma contain abundant biological information that reflect the body's physiological and pathological conditions and are therefore a valuable sample type for disease biomarkers. However, comprehensive profiling of the serological proteome is challenging due to the wide range of protein concentrations in serum. Methods: To address this challenge, we developed a novel in-depth serum proteomics platform capable of analyzing the serum proteome across ~10 orders or magnitude by combining data obtained from Data Independent Acquisition Mass Spectrometry (DIA-MS) and customizable antibody microarrays. Results: Using psoriasis as a proof-of-concept disease model, we screened 50 serum proteomes from healthy controls and psoriasis patients before and after treatment with traditional Chinese medicine (YinXieLing) on our in-depth serum proteomics platform. We identified 106 differentially-expressed proteins in psoriasis patients involved in psoriasis-relevant biological processes, such as blood coagulation, inflammation, apoptosis and angiogenesis signaling pathways. In addition, unbiased clustering and principle component analysis revealed 58 proteins discriminating healthy volunteers from psoriasis patients and 12 proteins distinguishing responders from non-responders to YinXieLing. To further demonstrate the clinical utility of our platform, we performed correlation analyses between serum proteomes and psoriasis activity and found a positive association between the psoriasis area and severity index (PASI) score with three serum proteins (PI3, CCL22, IL-12B). Conclusion: Taken together, these results demonstrate the clinical utility of our in-depth serum proteomics platform to identify specific diagnostic and predictive biomarkers of psoriasis and other immune-mediated diseases.
Asunto(s)
Quimiocina CCL22/genética , Medicamentos Herbarios Chinos/uso terapéutico , Elafina/genética , Subunidad p40 de la Interleucina-12/genética , Proteómica/métodos , Psoriasis/tratamiento farmacológico , Adulto , Biomarcadores/sangre , Proteínas Sanguíneas/clasificación , Proteínas Sanguíneas/genética , Proteínas Sanguíneas/metabolismo , Estudios de Casos y Controles , Quimiocina CCL22/sangre , Elafina/sangre , Femenino , Expresión Génica , Humanos , Subunidad p40 de la Interleucina-12/sangre , Masculino , Espectrometría de Masas , Medicina Tradicional China/métodos , Redes y Vías Metabólicas/efectos de los fármacos , Persona de Mediana Edad , Análisis de Componente Principal , Análisis por Matrices de Proteínas , Proteoma/clasificación , Proteoma/genética , Proteoma/metabolismo , Psoriasis/sangre , Psoriasis/diagnóstico , Psoriasis/patología , Índice de Severidad de la EnfermedadRESUMEN
Complementary DNAs encoding a previously unidentified mouse Notch ligand and its human ortholog were isolated. The new Notch ligand contains a signal sequence, a DSL domain, eight epidermal growth factor-like repeats, a transmembrane domain, and an intracellular region, all of which are characteristics of members of the Delta protein family. The new protein was therefore designated Delta-4. Several previously unidentified sequences in both the extracellular and intracellular regions were shown to be conserved among vertebrate Delta proteins. The tissue distribution of Delta-4 mRNA resembles that previously described for Notch-4 (Int-3) transcripts. However, in situ hybridization with mouse lung revealed that Delta-4 mRNA is abundant in squamous alveolar cells that neighbor endothelial cells; Notch-4 expression is largely restricted to the latter cell type. Soluble forms of the extracellular portion of Delta-4 inhibit the apparent proliferation of human aortic endothelial cells, but not human pulmonary arterial endothelial cells.