Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren's Syndrome Patients.

Patients with head and neck cancer (HNC) and patients with primary Sjögren's syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers.

Identification of tear-based protein and non-protein biomarkers: Its application in diagnosis of human diseases using biosensors.

Discovery of robust, selective and specific biomarkers are important for early diagnosis and monitor progression of human diseases. Eye being a common target for several human diseases, vision impediment and complications are often associated with systemic and ocular diseases. Tears are bodily fluids that are closest to eye and are rich in protein content and other metabolites. As a biomarker repository, it advantages over other bodily fluids due to the ability to collect it non-invasively. In this review, we highlight some recent advancements in identification of tear-based protein biomarkers like lacryglobin and cystatin SA for cancer; interleukin-6 and immunoglobulin-A antibody for COVID-19; tau, amyloid-ß-42 and lysozyme-C for Alzheimer's disease; peroxiredoxin-6 and α-synuclein for Parkinson's disease; kallikrein, angiotensin converting enzyme and lipocalin-1 for glaucoma; lactotransferrin and lipophilin-A for diabetic retinopathy and zinc-alpha-2 glycoprotein-1, prolactin and calcium binding protein-A4 for eye thyroid disease. We also discussed identification of tear based non-protein biomarkers like lysophospholipids and acetylcarnitine for glaucoma, 8-hydroxy-2'-deoxyquanosine and malondialdehyde for thyroid eye disease. We elucidate technological advancement in developing tear-based biosensors for diagnosis and monitoring diseases such as diabetes, diabetic retinopathy and Alzheimer's disease. Altogether, the study of tears as potential biomarkers for early diagnosis of human diseases is promising.

Transcriptomic analysis revealed increased expression of genes involved in keratinization in the tears of COVID-19 patients.

Recent studies have focused their attention on conjunctivitis as one of the symptoms of coronavirus disease 2019 (COVID-19). Therefore, tear samples were taken from COVID-19 patients and the presence of SARS-CoV-2 was evidenced using Real Time reverse transcription polymerase chain reaction. The main aim of this study was to analyze mRNA expression in the tears of patients with COVID-19 compared with healthy subjects using Next Generation Sequencing (NGS). The functional evaluation of the transcriptome highlighted 25 genes that differ statistically between healthy individuals and patients affected by COVID-19. In particular, the NGS analysis identified the presence of several genes involved in B cell signaling and keratinization. In particular, the genes involved in B cell signaling were downregulated in the tears of COVID-19 patients, while those involved in keratinization were upregulated. The results indicated that SARS-CoV-2 may induce a process of ocular keratinization and a defective B cell response.

Hypercytokinemia in COVID-19: Tear cytokine profile in hospitalized COVID-19 patients.

The aim of this study is to analyze the concentrations of cytokines in tear of hospitalized COVID-19 patients compared to healthy controls. Tear samples were obtained from 41 healthy controls and 62 COVID-19 patients. Twenty-seven cytokines were assessed: interleukin (IL)-1b, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor basic, granulocyte colony-stimulating factor (G-CSF), granulocyte-monocyte colony-stimulating factor (GM-CSF), interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1a, MIP-1b, platelet-derived growth factor (PDGF), regulated on activation normal T cell expressed and secreted, tumor necrosis factor-α and vascular endothelial growth factor (VEGF).In tear samples of COVID-19 patients, an increase in IL-9, IL-15, G-CSF, GM-CSF, IFN-γ, PDGF and VEGF was observed, along with a decrease in eotaxin compared to the control group (p < 0.05). A poor correlation between IL-6 levels in tear and blood was found. IL-1RA and GM-CSF were significantly lower in severe patients and those who needed treatment targeting the immune system (p < 0.05). Tear cytokine levels corroborate the inflammatory nature of SARS-CoV-2.