Evidence mapPaperPMID 41367913Full record

ArticleFrontiers in endocrinology2025

Discovery and serological validation of DAMP-derived B-cell epitopes as diagnostic biomarkers for diabetic nephropathy.

Chengyuan Yu, Yishi Dong, Fuhua Zhong, Jun Zeng, Zhiye Fang

Abstract readValidation Study
In one paragraph

Article in Frontiers in endocrinology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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5 authors.

Chengyuan YuGuangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, China.
Yishi DongGuangdong Provincial Clinical Research Center for Geriatrics, Shenzhen Clinical Research Center for Geriatrics, Department of Geriatrics, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, China.
Fuhua ZhongClinical Research Center, Shenzhen People's Hospital (The First Affiliated Hospital, Southern University of Science and Technology, The Second Clinical Medical College, Jinan University), Shenzhen, China.
Jun Zeng *Center for Medical Experiments, Shenzhen Guangming District People's Hospital, Shenzhen, China.
Zhiye Fang *Division of Respiratory Medicine, Shenzhen Guangming District People's Hospital, Shenzhen, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Diabetic nephropathy (DN), a severe complication of diabetes and a leading cause of end-stage renal disease, is strongly associated with chronic inflammation triggered by damage-associated molecular patterns (DAMPs), such as high-mobility group box 1 (HMGB1), S100A8, and S100A9. This study aimed to identify and validate conserved B-cell epitopes from these DAMPs to develop peptide-based serological markers for DN diagnosis. Methods: Canonical sequences of HMGB1 (NP_002119.2), S100A8 (NP_002955.1), and S100A9 (NP_002956.2) were retrieved from NCBI RefSeq. Evolutionary conservation was assessed using MAFFT v7.520 and ConSurf. Linear epitopes were predicted with BepiPred 2.0 (threshold = 0.5) and ABCpred (threshold = 0.51), while conformational epitopes were mapped using ElliPro (score ≥ 0.5, distance ≤ 6Å) on crystallographic structures (PDB: 2YRQ, 1XK4). Candidate epitopes were evaluated for antigenicity (VaxiJen v2.0, threshold = 0.5), surface accessibility (DSSP > 20%), and cross-reactivity (BLASTp against UniProtKB/Swiss-Prot 2024_03). Top peptides were synthesized via Fmoc-SPPS (≥ 95% purity, confirmed by HPLC/MS) and validated using indirect enzyme-linked immunosorbent assay (ELISA) on sera from DN patients ( Results: Three highly immunogenic and evolutionarily conserved linear B-cell epitopes were identified: HMGB1 (GSSGMGKGDPKKPRGK, VaxiJen = 1.60), S100A8 (NSIIDVYHKYSLIKGN, 1.20), and S100A9 (SVKLGHPDTLNQGEFK, 0.70). These epitopes overlapped with predicted conformational regions and were confirmed to be surface-exposed through structural modeling. ELISA analysis revealed significantly elevated IgG responses in DN patient sera versus controls ( Conclusion: This study successfully identified and validated three novel DAMP-derived B-cell epitopes with significant diagnostic potential for diabetic nephropathy. The peptides exhibited high immunogenicity, strong specificity, and consistent performance in ELISA-based serological assays. These findings pave the way for the development of noninvasive, peptide-based diagnostic tools for early DN detection. Future efforts will focus on multicenter validation and integration into multiplex serological panels.

Indexed as

Diabetic NephropathiesEpitopes, B-LymphocyteHMGB1 ProteinAdultAgedBiomarkersCase-Control StudiesFemaleHumansMaleMiddle AgedBiomarkersEpitopes, B-LymphocyteHMGB1 ProteinHMGB1 protein, humanB-cell epitopesdiabetic nephropathyHMGB1peptide-based diagnosticspeptide-based ELISAS100A8S100A9serological biomarkers

Identifiers

PMID41367913
PMCPMC12682578

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.