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Updated: Oct 19, 2026
Technique of Conjunctival Biopsy and Direct Immunofluorescence for Diagnosing Mucous Membrane Pemphigoid
Published on: June 17, 2025
CD74 as a Potential Adjunctive Tissue Biomarker for Bullous Pemphigoid Lesions: A Retrospective Study Integrating
Yuanlin Zhang1,2, Xiaolong Zhang1,2, Fei Dong1
1Department of Dermatology and Venereology, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
Background:
Bullous pemphigoid (BP), an autoimmune blistering disorder that primarily afflicts the geriatric population, poses diagnostic and therapeutic challenges, particularly in patients with comorbidities. This retrospective study aimed to identify and validate potential adjunctive tissue biomarkers for BP and explore their association with immune-related mechanisms through integrated bioinformatics analysis and experimental validation.
Methods:
Transcriptomic data from the GEO dataset were analyzed to identify differentially expressed genes (DEGs), which were further cross-referenced with immune-related gene signatures. CD74 was selected as a candidate biomarker and its expression was validated by immunohistochemistry (IHC) in paraffin-embedded skin tissues from patients with BP, healthy controls (HC), and disease controls, including pemphigus vulgaris (PV), psoriasis (Pso), atopic dermatitis (AD), and systemic lupus erythematosus (SLE). Diagnostic performance was evaluated by ROC curve analysis. Single-cell RNA sequencing and immunofluorescence staining were performed to investigate the cellular distribution and immune association of CD74.
Results:
CD74 was identified as an immune-related DEG associated with CCL13 expression. CD74 expression was increased in BP lesions and exhibited a characteristic linear distribution along the dermoepidermal junction. Quantitative ROC analysis based on CD74 expression area percentage showed moderate diagnostic performance, while the linear staining pattern demonstrated potential value as an adjunctive diagnostic feature. Single-cell RNA sequencing revealed predominant CD74 expression in MHC-II-enriched cells, and immunofluorescence confirmed CD74/HLA-DR colocalization. CD74 expression was positively correlated with peripheral blood eosinophil counts, suggesting an association with systemic immune activation in BP.
Conclusion:
CD74 may represent a promising adjunctive tissue biomarker for BP diagnosis. Its characteristic tissue distribution and association with immune-related features suggest that CD74 may reflect immune alterations within BP lesions. Further validation in larger independent cohorts is required.