Biopsy-Guided Cytokine Profiling as a Tool for Precision Medicine in Psoriasis

Psoriasis is a clinically heterogeneous inflammatory dermatosis characterized by diverse subtypes with variable therapeutic responses. While biologic therapies targeting TNF-α, IL-17, IL-23, and IL-36 pathways have transformed disease management, treatment selection remains largely empirical and is not routinely guided by tissue-level immune profiling. In this study, we performed quantitative immunohistochemical analysis of key cytokines, IL-17A, IL-17F, IL-23p19, IL-36γ, and TNF-α, across five psoriasis subtypes (guttate, inverse, palmoplantar, plaque, and pustular) using formalin-fixed paraffin-embedded skin biopsies. Cytokine-positive dermal cell populations were quantified using digital pathology, enabling subtype-specific comparison of inflammatory signatures. Distinct cytokine patterns were observed across subtypes. Pustular psoriasis demonstrated a prominent IL-17F and IL-36γ-dominant profile, whereas plaque psoriasis exhibited broad cytokine expression with relative IL-17A predominance. Palmoplantar psoriasis showed a mixed IL-17/IL-36 signature, while guttate and inverse subtypes displayed comparatively attenuated inflammatory profiles. Because cytokine expression was quantified within the dermal compartment, these findings should be interpreted as dermal inflammatory patterns rather than as measures of total tissue cytokine expression, particularly for IL-36γ, which is also strongly associated with keratinocyte-derived epidermal responses. These findings provide tissue-level evidence of immunologic heterogeneity across psoriasis subtypes and support the concept of cytokine-driven disease endotypes. Biopsy-based cytokine profiling may represent a promising, hypothesis-generating approach for characterizing lesion-specific inflammatory patterns and potentially informing individualized therapeutic strategies, although prospective studies linking tissue profiles with treatment response are required to establish clinical utility.