Title : Translating genetic and immune insights into psoriasis management
Abstract:
Psoriasis is a chronic inflammatory and proliferative disorder of the skin with autoimmune mechanisms, genetic predisposition, and important systemic associations. Clinically, it is characterized by well-defined erythematous, scaly, indurated plaques predominantly involving the extensor surfaces and scalp. Advances in molecular genetics and immunology over recent decades have considerably improved the understanding of psoriasis pathogenesis and have significantly influenced therapeutic strategies.
Both genetic and environmental factors contribute to the development and expression of psoriasis. The bimodal age distribution of onset suggests two pathogenetically distinct forms of the disease. Type I psoriasis, which accounts for the majority of cases, is hereditary in nature, strongly associated with HLA-C*06:02, presents early in life, and is usually more severe. Type II psoriasis is generally sporadic, unrelated to HLA status, occurs later in life, and tends to follow a milder course. Familial clustering, autosomal dominant inheritance with reduced penetrance, and higher concordance rates in monozygotic twins compared to dizygotic twins further support the genetic basis of the disease.
Psoriasis is currently regarded as a polygenic and multifactorial disorder in which multiple susceptibility genes interact with environmental triggers to produce disease expression. Genome-wide association studies have identified several susceptibility loci, particularly the PSORS1 locus within the HLA region, along with immune-regulatory genes such as IL23R, TNFAIP3, CARD14, and STAT3. These discoveries have highlighted the central role of the IL-23/Th17 pathway in disease pathogenesis. Cytokines including TNF-α, IL-17, IL-22, and IL-23 contribute to sustained inflammation, keratinocyte proliferation, and systemic immune dysregulation.
Improved understanding of these molecular and immunological mechanisms has resulted in a major therapeutic transition from nonspecific immunosuppression to targeted biologic therapy. Agents directed against TNF-α, IL-17, and IL-23 pathways have demonstrated remarkable efficacy in achieving disease control, prolonged remission, and improved quality of life. Emerging therapies involving Janus kinase inhibitors, small-molecule modulators, tissue-resident memory T-cell targeting, and microbiome-based interventions continue to expand the therapeutic landscape.
The concept of precision dermatology is gaining increasing importance in psoriasis management. Genetic profiling, immune biomarkers, and pharmacogenomics may eventually help predict disease severity, therapeutic response, risk of psoriatic arthritis, and long-term outcomes, thereby facilitating individualized treatment strategies. Continued translational research integrating genetics, immunology, and therapeutics is expected to further refine psoriasis management and improve long-term patient outcomes.Top of Form
