# The Immunogenetics of Psoriasis and Implications for Drug Repositioning
## 1 Introduction  
Psoriasis is a clinically common chronic inflammatory disease. Psoriasis patients experience skin tissue damage and can also simultaneously develop other systemic complications. This disease usually manifests with clinical and histological features, such as oval-shaped plaques with adherent, uplifted silver scales, dividing lines, and erythema. Scales are formed due to the incomplete keratinization of keratinocytes, which consists of prematurely overproliferated epidermal and cuticle-retained nuclei (parakeratosis). Compared to normal skin, an increased rate of mitosis in basal keratinocytes is observed. Since psoriasis is a skin-specific T-cell-mediated autoimmune disease, epidermal growth factors, nerve growth factors, adhesion factors, chemokines, neuropeptides, and T-cell receptors are involved in its pathogenesis. This disease affects approximately 1-3% of the world's population [1]. Even after continuous developments and progress, the incidence of skin diseases continues to increase [2].  
Epidemiological studies have established a genetic basis for psoriasis, with an estimated heritability of 60-90%, which is the highest among complex genetic diseases [3]. Familial studies have indicated higher incidences among primary and secondary relatives of psoriasis patients than among the general population, and three times the likelihood of incidence among identical twins than that of fraternal twins [4]. Approximately 70% of children with psoriasis present with family history of the disease [5]. Even though the genetic mechanisms of psoriasis are complex, a plausible explanation for its pathogenesis can be attributed to the abnormal activation of T cells and their migration into the skin, leading to the accumulation of inflammatory cells. CD4+ and CD8+ T cells then co-regulate the development of psoriatic lesions [5, 6]. This hypothesis further confirms the importance of immunization in counteracting the pathogenicity of psoriasis.  
Although the exact cause of psoriasis remains unknown, immune factors play a very important role in its pathogenesis. The use of immunotherapy has received increased attention due to the rapid progress in understanding the immune system-related psoriatic mechanisms. In fact, the psoriasis drug market is currently dominated by various types of antibody-based drugs [7]. Since psoriasisis a chronically recurrent disease, many patients require long-term treatment. However, up to 30% of the patients treated with anti-tumor necrosis factor (_TNF_) drugs (such as adalimumab) respond inadequately, and up to 50% lose response over time [8]. Even though anti-_IL-17A_ drugs show better safety profiles compared to anti-TNF agents, they are often associated with an increased risk of severe infection and allergic, immunological, or other unwanted reactions [9]. Therefore, the biggest concern regarding these immunotherapies is with respect to their safety. The continued development of effective therapies for psoriasis is urgently needed. Drug repositioning (the application of approved drugs for new therapies) has provided an efficient route for drug discovery. It has the potential to greatly benefit affected patients by analyzing the immunogenic mechanism of psoriasis. In this paper, following the analysis of the immunogenic mechanism of psoriasis, we show the great potential of genetics-directed drug repositioning [10] in psoriasis treatment.