Assess serum and tissue retinol binding protein 4 in patients with severe alopecia areata in correlation with healthy individuals .

Estimate genetic profile of retinol binding protein4 in severe alopecia areata patients

Assess possible role of retinol binding protein 4 genetic mutation in response to barcitinib treatment in patients with severe alopecia areata .

Alopecia areata is an autoimmune disorder characterized by transient, non-scarring hair loss and preservation of the hair follicle .It is a multifactorial disease in which environmental, neuro-endocrinological, immunological and genetic factors are involved . AA affecting the hair follicle is the most common form, through a breakdown in immune privilege of the hair follicle in the anagen (hair growth) phase by CD4+ and CD8+ T lymphocytes .

Based on the degree of hair loss and variation in clinical presentation, AA classified into patchy (AA; localized areas of hair loss on the scalp and/or body), totalis (AT; entire scalp hair loss), and universalis (AU; entire scalp and body hair loss . Several studies showed that genes involved in immune response , inflammatory diseases . infectious diseases .The hair loss in AA involves changes in the hair growth cycle, resulting in dystrophic anagen hair follicles together with increased frequency of telogen follicles.

Retinol binding protein 4 (RBP4) is a member of the lipocalin family and the major transport protein of the hydrophobic molecule retinol, also known as vitamin A, in the circulation. Expression of RBP4 is highest in the liver, where most of the body's vitamin A reserves are stored as retinyl esters. For the mobilization of vitamin A from the liver, retinyl esters are hydrolyzed to retinol, which then binds to RBP4 in the hepatocyte . The pathogenesis of AA may be related to increased serum retinol-binding protein-4 (RBP4) level. Its level was found to be increasing in the outer root sheath during late anagen and remained as such throughout catagen. RBP4 may contribute to inflammation by stimulating the expression of proinflammatory molecules involved in leukocyte recruitment and adherence to the endothelium .

Baricitinib (bar" i sye' ti nib) is an orally available, specific inhibitor Janus-associated kinases (mainly JAK1 and JAK2) that is used to treat moderate-to-severe rheumatoid arthritis and alopecia areata. The Janus kinases are critical steps in immune activation as well as in hematopoiesis. JAK1 is a critical kinase in the cellular responses of interferon alpha while JAK2 is involved in pathways activated by interferon gamma. The immunomodulatory effects of baricitinib have led to its evaluation in several autoimmune conditions interrupt cytokine signaling implicated in the pathogenesis of alopecia areata .

Inclusion Criteria:

• Patients at least 12 years old not more than 60 with severe alopecia areata, multiple or /with not responding to usual treatment

Exclusion Criteria:

• Patients with scarring alopecia.
• Patients less than 12 years old or more than 60.
• Patients with active inflammatory disease or immuncompromised.
• Patients with infection or malignancy .
• Patients with antiepileptic drugs or psychotics .
• Pregnancy and lactation .
• Patients with abnormal lipid profile.
• Patients with bleeding or thrombotic tendency.
• Patients taking other JAK inhibitors or cyclosporine or immunosuppressive drugs.
• Patients with active herpes zoster or have tendency for recurrence.

asses level of retinol binding protein 4 before and after barcitinib treatment.