Evaluation of IL 12B Genetic Polymorphism (rs3213094) in Patient With Psoriasis and Psoriatic Arthritis in Response to Humira

Psoriasis is known to be affecting 3% to 4% of the general population worldwide. While the prevalence of psoriasis in Egypt ranges 0.19-3% Psoriatic arthritis (PsA) most commonly develops in 20-30% of psoriatic patients with preceding psoriasis or develops concomitantly with psoriasis, and it manifests all features of arthritis, including enthesitis.

The pathogenesis of psoriasis is multifactorial, involving a complex interplay between genetic predisposition, immune system dysregulation, and environmental triggers. Central to the disease process is the activation of T-cells, particularly Th1, Th17, and Th22 subsets, which release pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-17 (IL-17), and interleukin-22 (IL-22)

. These cytokines drive the abnormal growth and differentiation of keratinocytes and induce the inflammatory cascade that results in the characteristic skin lesions. Genetic factors, including polymorphisms in genes related to the immune system, such as HLA-Cw6.Additionally, environmental factors like infections, stress, and trauma (Koebner phenomenon) can exacerbate or trigger the onset of the disease.

The Psoriasis Area and Severity Index (PASI) is a widely used tool for assessing the severity of psoriasis and evaluating treatment efficacy. It combines the extent of skin involvement and the degree of erythema, scaling, and thickness across four body regions: the head, upper limbs, trunk, and lower limbs. Each region is assigned a score for surface area involvement (0-6) and for each symptom (0-4), which are then combined to yield an overall PASI score ranging from 0 to 72. Higher scores indicate more severe disease. Typically, a PASI score below 10 suggests mild psoriasis, while scores between 10 and 20 indicate moderate severity, and scores above 20 reflect severe psoriasis. PASI serves as a critical endpoint to gauge disease burden.

Interleukin-12B (IL12B) encodes the p40 subunit shared by both IL-12 and IL-23, cytokines that are pivotal in the differentiation of naive T-cells into Th1 and Th17 cells, respectively. The IL-12/IL-23 axis is well-established in contributing to the immune pathology seen in psoriasis. Genetic studies have shown that polymorphisms within the IL12B gene are associated with an increased risk of psoriasis.