Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation

Aditi Gadre; Taylor Dyson; Jaroslaw Jedrych; Grant Anhalt; Angel S Byrd; Crystal Aguh

doi:10.1016/j.xjidi.2024.100263

Proteomic Profiling of Central Centrifugal Cicatricial Alopecia Reveals Role of Humoral Immune Response Pathway and Metabolic Dysregulation

JID Innov. 2024 Jan 28;4(3):100263. doi: 10.1016/j.xjidi.2024.100263. eCollection 2024 May.

Authors

Aditi Gadre^{1

2}, Taylor Dyson^{1

3}, Jaroslaw Jedrych¹, Grant Anhalt¹, Angel S Byrd^{1

4}, Crystal Aguh¹

Affiliations

¹ Department of Dermatology, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
² School of Medicine, Georgetown University, Washington, District of Columbia, USA.
³ Eastern Virginia Medical School, Norfolk, Virginia, USA.
⁴ Department of Dermatology, College of Medicine, Howard University, Washington, District of Columbia, USA.

Abstract

Proteomic profiling on other primary cicatricial alopecias, such as frontal fibrosing alopecia and lichen planopilaris, have suggested a T helper 1-mediated inflammatory pathway, but in central centrifugal cicatricial alopecia (CCCA), the protein expression patterns are unknown. In this study, we sought to characterize protein expression patterns in CCCA to identify biomarkers of disease activity that will identify potential therapeutic avenues for treatment. Scalp protein quantification was performed to understand protein expression patterns in affected versus unaffected scalps in CCCA. A total of 5444 proteins were identified, of which 148 proteins were found to be differentially expressed in CCCA-affected scalp, with upregulation of adaptive immune pathways (IGHG3, P = .034; IGHG4, P = .01; IGG1, P = .026) and markers of fibrosis (ITGA1, P = .016; SFRP2, P = .045; TPM2, P = .029; SLMAP, P = .016) and downregulation of metabolic proteins (ALOX15B, P = .003; FADS2, P = .006; ELOVL5, P = .007; FA2H, P = .017; FAR2, P = .011; SC5D, P < .001). Our analysis revealed, to our knowledge, previously unknown humoral immune canonical pathways, notably IgG, implicated in CCCA and additionally confirmed aberrant lipid metabolism pathways implicated in diabetes mellitus, suggesting unique mechanisms of disease in patients with CCCA.

Keywords: Ethnic skin; Fibrosis; Hair loss; Scarring alopecia; Transcriptomics.