PXD075349-1

PXD075349 is an original dataset announced via ProteomeXchange.

Title	Integrative Plasma Proteomics and Myeloid-Interferon Profiling Reveal an AI-Validated Vascular-Endothelial Stress Signature Distinguishing SLE Flare from Remission in an Indian Cohort A Discovery – Phase Study
Description	Background: Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder characterized by unpredictable flares and variable clinical quiescence. Despite validated clinical indices like the British Isles Lupus Assessment Group (BILAG) score, reliable molecular biomarkers for monitoring disease activity remain limited, particularly in underrepresented South Asian populations. We aimed to identify a robust molecular framework to distinguish SLE flares from remission in an Indian cohort. Methods: We conducted a discovery-phase study in an Indian cohort (n=16) stratified by Easy-BILAG scoring. Plasma proteomic profiling via LC-MS/MS was integrated with targeted cytokine quantification using the Olink Proximity Extension Assay (PEA). Differential expression and network analyses delineated immune-regulatory, hypoxic-vascular, and myeloid-activation pathways. A Random Forest classifier was trained on selected biomarkers and evaluated using leave-one-out cross-validation (LOOCV), permutation testing, and bootstrapped AUROC confidence intervals, with model interpretability assessed by SHAP values. Results: Proteomic comparison identified a compact panel of proteins distinguishing flare from remission, characterized by a molecular polarization; flare states exhibited upregulation of COL18A1 and CSF1 (vascular and myeloid activation), while remission showed sustained expression of cytoskeletal scaffolding and immunoregulatory components, including FLNA, SH3BGRL3, and IGHG4. Cytokine analyses identified coordinated chemokine modules (CXCL9, CCL2, CCL3, and CCL13) preferentially upregulated during flare. The machine-learning model achieved robust internal discrimination with a mean AUROC of 0.96. Notably, a COL18A1 normalized protein expression cut-off yielded 100% specificity and 87.5% sensitivity, acting as an objective 'rule-in' adjunct for active disease. (NPX) cut-off yielded 100% specificity and 87.5% sensitivity, acting as an objective "rule-in" adjunct for active disease. Conclusions: This study establishes a parsimonious 5-protein biosignature (COL18A1, HYOU1, IGHG4, FLNA, and SH3BGRL3) that effectively captures the multifactorial pathophysiology of SLE flare. By anchoring discovery in a systematically under sampled Indian population, this work enhances global diversity in lupus biomarker research and establishes a scalable, AI-driven framework for precision assessment of disease activity.
HostingRepository	PRIDE
AnnounceDate	2026-06-22
AnnouncementXML	Submission_2026-06-21_16:09:11.042.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Abhibroto Karmakar
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-07 07:54:21	ID requested
⏵ 1	2026-06-21 16:09:11	announced

Karmakar A, Mishra S, Kumar U, Kamath R, Ravindran V, Suryakanth VB, Prabhu S, Nagaraju SP, Prabhu MM, Karmakar S, Integrative plasma proteomics and myeloid- interferon profiling reveal an AI-validated vascular- endothelial stress signature distinguishing SLE flare from remission in an Indian cohort a discovery - phase study. Front Immunol, 17():1819049(2026) [pubmed]

10.3389/fimmu.2026.1819049;

submitter keyword: Biomarker, SHAP values, Explainable AI (XAI),Cytokine, Multi-omics, Machine learning, Proteomics, precision medicine

Dr. Mukhyaprana M Prabhu
contact affiliation	Department of General Medicine, Kasturba Medical College, Manipal, Manipal Academy of Higher Education
contact email	mm.parbhu@manipal.edu
lab head
Abhibroto Karmakar
contact affiliation	Department of General Medicine, Kasturba Medical College,Manipal, Manipal Academy of Higher Education, India
contact email	abhibroto.karmakar@learner.manipal.edu
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2026/06/PXD075349

PRIDE project URI

• PRIDE
  1. PXD075349
     1. Label: PRIDE project
     2. Name: Integrative Plasma Proteomics and Myeloid-Interferon Profiling Reveal an AI-Validated Vascular-Endothelial Stress Signature Distinguishing SLE Flare from Remission in an Indian Cohort A Discovery – Phase Study