Comprehensive profiling of humoral antibody response to severe acute respiratory
syndrome (SARS) coronavirus-2 (CoV-2) proteins is essential in understanding the host
immunity and in developing diagnostic tests and vaccines. To address this concern, we
developed a SARS-CoV-2 proteome peptide microarray to analyze antibody interactions at
the amino acid resolution. With the array, we demonstrate the feasibility of employing
SARS-CoV-1 antibodies to detect the SARS-CoV-2 nucleocapsid phosphoprotein. The first
landscape of B-cell epitopes for SARS-CoV-2 IgM and IgG antibodies in the serum of 10
coronavirus disease of 2019 (COVID-19) patients with early infection is also
constructed. With array data and structural analysis, a peptide epitope for neutralizing
antibodies within the SARS-CoV-2 spike receptor-binding domain’s interaction
interface with the angiotensin-converting enzyme 2 receptor was predicted. All the
results demonstrate the utility of our microarray as a platform to determine the changes
of antibody responses in COVID-19 patients and animal models as well as to identify
potential targets for diagnosis and treatment.
COVID-19 has quickly become a worldwide pandemic, which has significantly impacted the economy, education, and social interactions. Understanding the humoral antibody response to SARS-CoV-2 proteins may help identify was not certified by peer review)
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.
Let M C R "+i be a compact connected smooth hypersurface, and Iet W C l:t "*+i be the area bounded by M. We study the question: Does W contain a principal centre of curvature for some point of M?
Coronavirus disease 2019 (COVID-19) is a highly contagious infection and threating the human lives in the world. The elevation of cytokines in blood is crucial to induce cytokine storm and immunosuppression in the transition of severity in COVID-19 patients. However, the comprehensive changes of serum proteins in COVID-19 patients throughout the SARS-CoV-2 infection is unknown. In this work, we developed a high-density antibody microarray and performed an in-depth proteomics analysis of serum samples collected from early COVID-19 (n=15) and influenza (n=13) patients. We identified a large set of differentially expressed proteins (n=132) that participate in a landscape of inflammation and immune signaling related to the SARS-CoV-2 infection. Furthermore, the significant correlations of neutrophil and lymphocyte with the CCL2 and CXCL10 mediated cytokine signaling pathways was identified. These information are valuable for the understanding of COVID-19 pathogenesis, identification of biomarkers and development of the optimal anti-inflammation therapy.
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