Proteomic profiling reveals distinct inflammatory and neurogenic endotypes in rosacea - 18/12/25

Doi : 10.1016/j.jaad.2025.08.014

Jundong Huang, MD ^a,^b, Yifan Zhang, MD ^a,^b, Caitan Yi, MD ^a,^b, Xin Xiao, MD ^a,^b, Dan Jian, MD ^a,^b,^c,^d, Wei Shi, MD ^a,^b,^c,^d, Fangfen Liu, MD ^a,^b,^c,^d, Yingxue Huang, MD ^a,^b,^c,^d, Zhixiang Zhao, MD ^a,^b,^c,^d, Yan Tang, MD ^a,^b,^c,^d, Mengting Chen, MD ^a,^b,^c,^d, Zhili Deng, MD ^a,^b,^c,^d, Ji Li, MD ^a,^b,^c,^d, Yiya Zhang, MD, PhD ^a,^b,^c,^d,^⁎ , Ben Wang, MD, PhD ^a,^b,^c,^d,^⁎
^a Department of Dermatology, Xiangya Hospital, Central South University, Changsha, China
^b Hunan Key Laboratory of Aging Biology, Xiangya Hospital, Central South University, Changsha, China
^c National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
^d FuRong Laboratory, Changsha, China

^∗Correspondence to: Ben Wang, MD, PhD, and Yiya Zhang, MD, PhD, Department of Dermatology, Xiangya Hospital, Central South University, 87 Xiangya Rd, Changsha, Hunan, China.Department of DermatologyXiangya HospitalCentral South University87 Xiangya RdChangshaHunanChina

Abstract

Background

Rosacea represents a chronic inflammatory dermatosis with potential systemic manifestations. While neuroimmune dysregulation and systemic inflammation are implicated in its pathogenesis, comprehensive proteomic profiling remains unexplored.

Objective

To characterize serum proteomic signatures and identify molecular endotypes in rosacea.

Methods

Using a prospectively characterized clinical cohort, we conducted quantitative proteomic profiling of serum samples from 27 rosacea patients and 25 healthy controls matched for age and sex. Bioinformatic analyses then correlated differentially expressed serum proteins with clinical symptom measures.

Results

Analysis identified 490 differentially expressed proteins (431 upregulated, 59 downregulated; log2FC > 1, P < .05). Downregulated proteins were enriched in complement pathways, while upregulated proteins implicated inflammatory (PI3K-Akt, IL-17), metabolic (cholesterol), and neuroregulatory pathways. Cluster analysis revealed 2 distinct endotypes: an inflammatory-predominant subtype ( n = 22) and a neurogenic-metabolic subtype ( n = 5). Integrative biomarker analysis revealed distinct molecular signatures for rosacea symptoms. Flushing was linked to neutrophil-driven inflammation and lipid metabolism (46 proteins), while burning was associated with neuronal repair and complement activation (120 proteins).

Limitations

Cross-sectional design and female-predominant cohort.

Conclusion

This pioneering proteomic study establishes rosacea as a systemic inflammatory disorder with distinct molecular endotypes, supporting tailored therapeutic approaches targeting neuroimmune-metabolic dysregulation.

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Key words : endotypes, neurogenic inflammation, proteomic profiling technology, rosacea, serum, systemic inflammatory

Abbreviations used : IRB, CEA, FAST, IGA, HS, FA, KEGG, GO, DIA, PCA, DEPs, LC-MS/MS, I3K

Mappa

Introduction

Materials and methods

Population characteristics

Serum proteome sample preparation

Data-independent acquisition analysis

Bioinformatic analysis

Results

Pathway analysis distinguishes disease-specific proteomic profiles

Serum biomarkers correlate with subjective symptoms

Cluster analysis of patients with rosacea identified 2 clusters with differing protein signatures

Discussion

	Drs Huang, Zhang and Yi have contributed equally to this work and share first authorship.
	Funding sources: This work was supported by grants from National Natural Science Funds for Distinguished Young Scholars (No. 82225039 ), National Natural Science Funds for Excellent Young Scientists (No. 82422063 ), National Key Research and Development Program of China (No. 2023YFC2509003 ) and the National Natural Science Foundation of China (No. 82473545 , 82173448 , 82203958 , 82273557 , 82473554 ), Natural Science Foundation of Hunan province in China (No. 2024JJ5577 ), the Program of Youth Talent Support for Changsha City (No. kq2506003).
	Patient consent: Consent for the publication of patient blood samples or other identifiable material was obtained by the authors and included at the time of article submission to the journal stating that all patients gave consent with the understanding that this information may be publicly available.
	IRB approval status: Reviewed and approved by the institutional research ethics boards of Xiangya Hospital; approval #2025030364.

Esportazione

Vol 94 - N° 1

P. 66-72 - gennaio 2026 Ritorno al numero

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Proteomic profiling reveals distinct inflammatory and neurogenic endotypes in rosacea - 18/12/25

Abstract

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Conclusion

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