Polymorphism of Janus Kinase 1 and 2 (JAK 1&2) in Patients With Alopecia Areata

Introduction Alopecia areata (AA) is a complex inflammatory disease characterized by cellular infiltration of T- lymphocytes targeting hair follicles, disrupting the anagen phase, with spontaneous remission, recurrence, and exacerbation, making it very unpredictable and emotionally disturbing . It affects nearly 1-2% of the general population with a lifetime risk of 2%, The onset of AA might be at any age; however, most patients develop the disease before 40 years of age . Early-onset AA (a mean age of onset at 5-10 years) predominantly presents as a more severe subtype, such as alopecia universalis . Alopecia areata presents clinically as a non-scarring patchy hair loss primarily on the scalp, and/or other hairy areas and may progress to total scalp hair loss (alopecia totalis, AT ) or complete body hair loss (alopecia universalis, AU ) . Approximately 5- 10% of AA patients will progress into AT/AU . The course of AA varies greatly, the strongest predictors of a poor prognosis include AT, AU, or ophiasis pattern hair loss, as well as earlier age of onset . Severe and recurrent AA disturbs quality of life of patients and may also lead to depression, changed self-image,and interferes with social activities . Currently, the hypotheses for AA development mostly focus on the collapse of immune privilege properties of the hair follicles(HFs) and the nature of self-antigen presentation (follicular antigens) that result in the induction and subsequent attack of activated lymphocytes . Activation of the lymphocytes mainly CD8+NKG2D+induces release of severalTh1 cytokines; interleukin (IL)-1α , IL-1β , and tumor necrosis factor (TNF) alpha, capable of inhibiting (HF) growth with early termination of anagen . AA is a polygenic disorder in which several major genes dictate susceptibility to disease, up to 28% of patients report at least one affected family member, monozygotic twins have exhibited similar times of onset and patterns of hair loss.

Genes loci for Human leucocyte antigens (HLA)DRB1* 1104 and DQB1* 03 are detected in patients with AA. The Janus kinases (JAKs) and signal transducer and activator of transcription (STAT); (JAK/STAT) pathway play an important role in inflammatory processes as they are involved in signaling for over 50 cytokines and growth factors. The JAK/STAT pathway transduces multiple extracellular signals involved in cell proliferation, differentiation, migration, and apoptosis .

The JAK family is constituted by four types of cytoplasmic tyrosine kinases:

JAK1, JAK2, JAK3, and TYK2 . STAT, of which there are seven different subtypes (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6) (17), is the other fundamental component of the cascade . After being phosphorylated by JAK, STAT translocates to the nucleus to induce the transcription of specific genes. Alterations in the JAK/STAT pathway have been related to the pathophysiology of atopic dermatitis (AD), vitiligo, and AA.