Dataset Information

Cutaneous Lupus Erythematosus: proteomics salivary profiling

ABSTRACT: Background: Cutaneous lupus erythematosus (CLE) is a complex autoimmune condition with limited data on its molecular underpinnings. Saliva, as plasma filtrate fluid may be a promising tool for biomarkers discovery, since it is an easily accessible biofluid. This study aimed to characterize the salivary proteomic profile of CLE patients compared to healthy controls, to identify potential disease-specific biomarkers. Methods: Ten females diagnosed with CLE and twelve controls without autoimmune conditions were included in the study. Saliva samples were collected under controlled conditions and analyzed using mass spectrometry and chromatography. Proteomic analysis was performed with the nanoElute nanoflow system coupled to a timsTof-Pro mass spectrometer. Results: Among the 104 proteins identified, six showed statistically significant differences between groups. PEBP1 (RKIP), ARG1, TALDO, and CTSZ were upregulated in CLE, while TFF3 and PRDX4 were absent. These proteins are involved in immune regulation, metabolic processes, redox balance, and inflammation. RKIP and ARG1 showed high discriminatory power (AUROC = 1.0), suggesting their potential as CLE biomarkers. Conclusion: This study establishes a distinct salivary proteomic signature in CLE, highlighting a panel of proteins with diagnostic potential. The use of saliva and proteomic techniques offers a powerful approach to unravel CLE pathophysiology and supports future research on non-invasive biomarkers for disease monitoring and personalized care.

INSTRUMENT(S):

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Saliva

DISEASE(S): Cutaneous Lupus Erythematosus

SUBMITTER: Giovanna Florezi

LAB HEAD: Carlos Alberto Labate

PROVIDER: PXD064580 | Pride | 2025-12-22

REPOSITORIES: Pride

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Salivary proteomics profiling in cutaneous lupus erythematosus.

Florezi Giovanna P GP Barone Felippe P FP Labate Mônica T V MTV Labate Carlos A CA Nico Marcello M S MMS Lourenço Silvia V SV

Lupus 20251218

BackgroundCutaneous lupus erythematosus (CLE) is a complex autoimmune condition with limited data on its molecular underpinnings. Saliva, as plasma filtrate fluid may be a promising tool for biomarkers discovery, given its easy accessibility.ObjectiveThis study aimed to characterize the salivary proteomic profile of CLE patients compared to healthy controls to identify potential disease-specific biomarkers.MethodsTen females diagnosed with CLE and eleven controls without autoimmune conditions we ...[more]

PMID: 41408937

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Project description:Saliva, a biofluid enriched in biological omic constituents, has emerged as a promising source for exosomal biomarkers due to its easy accessibility. Despite the understanding of the coronavirus disease-19 (COVID-19), the role of Salivary Extracellular Vesicles (sEVs) in COVID-19 remains poorly understood. Exploring the proteomic cargo of sEVs could prove valuable for diagnostic and prognostic purposes in assessing COVID-19. The proteomic cargo of sEVs from COVID-19 (+) subjects and their healthy close contacts (HCC) was explored. Nine COVID-19 positive (+) patients and eleven in-house close contact patients identified by real-time quantitative polymerase chain reaction (RT-qPCR) of nasopharyngeal swabs were included. In-house close contacts were defined as individuals with a negative RT-qPCR result sharing a residence with a confirmed COVID-19 case. sEVs were isolated by ultracentrifugation from unstimulated saliva samples, and subsequently characterized through nanoparticle tracking, transmission electron microscopy, and western-blot analyses. The proteomic cargo of sEVs was processed by LC-MS/MS. sEVs were morphologically compatible with EVs, with the presence of Syntenin-1 and CD81 EVs markers. The sEVs proteome showed 1,417 proteins: 1,288 in COVID-19 (+) cases and 1,382 in HCC. 35 proteins were found exclusively and 89 were more abundant in sEVs from COVID-19 (+) subjects. “Coronavirus disease response”, “complement and coagulation cascades”, and “PMN extracellular trap formation” were the most enriched KEGG pathways in COVID-19 (+) cases. The most represented biological processes were “Hemoglobin and haptoglobin binding” and “oxygen carrier activity”, and the best-denoted molecular functions were “regulated exocytosis and secretion” and “leucocyte and PMN mediated immunity”. We suggest that sEVs proteomic cargo in COVID-19 is related to immune response processes, oxygen transport, and antioxidant mechanisms. In contrast, in HCC, sEVs signature profiles are mainly associated with epithelial homeostasis.

Project description:This is a pilot study. We are trying to detect potential salivary biomarkers in mice with a pancreatic tumor. Global gene expression profiling has shown great promise in high-throughput biomarker discovery for early disease detection in body fluids such as saliva, which is accessible, cost-effective, and non-invasive. However, this goal has not been fully realized because saliva, like many clinical samples, contains partially fragmented and degraded RNAs that are difficult to amplify and detect with prevailing technologies. Here, using nanogram scale salivary RNA as a proof-of-principle example, we describe our progress with a novel poly-A tail independent mRNA amplification strategy combined with the Affymetrix GeneChip Exon arrays. We defined a Salivary Exon Core Transcriptome (SECT) with highly similar expression profiles in healthy individuals verified by quantitative PCR. Informatics analysis of SECT provided important mechanistic insight to their potential origin and function. Finally we demonstrated the diagnostic potential of true exon level expression profiling approach with salivary exon biomarkers that accurately discriminated gender in healthy individuals. Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of biological and mechanistic rationale why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Pan02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineered a Pan02 cell line that is suppressed for exosome biogenesis, implanted into the C56BL/6 mouse and examine if the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases. We analyzed saliva from 6 healthy mice and 6 mice with a pancreatic tumor using the Affymetrix Mouse Exon Genome 430 2.0 platform. Array data was processed by dChip. No techinical replicates were performed.

			Action	DRS
	RAW_CLE.zip	Other
	checksum.txt	Txt
	mqpar.xml	Xml
	peptides.txt	Txt
	proteinGroups.txt	Txt