Psoriasis and Leprosy: An Arcane Relationship

Area of Science:

• Immunology
• Dermatology
• Genomics

Background:

• Psoriasis (Ps) and leprosy are chronic inflammatory skin diseases with distinct immune system involvements.
• The rare coexistence of psoriasis and leprosy suggests underlying molecular immune mechanisms that remain unclear.

Purpose of the Study:

• To investigate the molecular immune mechanisms underlying the rare coexistence of psoriasis and leprosy.
• To identify differentially expressed genes (DEGs) and key biological pathways distinguishing psoriasis from leprosy.

Main Methods:

• RNA-sequencing (RNA-seq) was performed on skin biopsies from patients with psoriasis, lepromatous leprosy (L-lep), and tuberculoid leprosy (T-lep).
• Bioinformatic analyses including Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), Gene Set Enrichment Analysis (GSEA), and protein-protein interaction (PPI) networks were employed.
• Key DEGs were validated using quantitative real-time polymerase chain reaction (qRT-PCR).

Main Results:

• The protein-protein interaction (PPI) network highlighted immune response, IL-17 signaling, and Toll-like receptor pathways differentiating psoriasis and leprosy.
• Th17 markers (e.g., IL-17A, IL-19, IL-20, IL-36A, IL-36G, IL-22, LCN2) were upregulated in psoriasis compared to both L-lep and T-lep.
• Macrophage biomarkers (CLEC4E, TREM2), SPP1, and dendritic cell (DC)-related markers (ITGAX) along with TNF-a showed lower expression in psoriasis and T-lep compared to L-lep.

Conclusions:

• Elevated expression of IL-17 pathway markers and LCN2 in psoriasis patients may confer resistance to lepromatous leprosy.
• High expression of CLEC4E, TREM2, and SPP1 in lepromatous leprosy patients suggests they are unlikely to concurrently have psoriasis.
• Distinct molecular immune signatures differentiate psoriasis and leprosy, explaining their rare coexistence.