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Pemphigus is a group of autoimmune diseases that affect the skin and the mucous membranes. Several subtypes of pemphigus have been identified, based on clinical and histologic features as well as on the specific antigens targeted by circulating autoantibodies.Pemphigus vulgaris (PV) is the most prevalent type of pemphigus, comprising up to 70% of all cases of pemphigus. [1] PV is characterized by acantholysis and intraepidermal blister formation, resulting from IgG autoantibodies directed against transmembrane desmosomal glycoprotein desmoglein 3 and in some cases desmoglein 1. [2,3] However, many immunological steps are required prior to autoantibody production that is the key to the development of blisters in pemphigus.Interleukin-1 receptor-activated kinases (IRAKs) are key mediators in the IRAK1/NF-κB signalling pathway. IRAK1 plays a significant role in NF-κB activation, which subsequently increases the expression of many genes related to immunological reactions. [4,5] NF-kB is inactivated by cytoplasmic trapping through IkB proteins (eg NFKBIA). Phosphorylation of serine residues on the I kappa B proteins, by kinases, marks them for destruction via the ubiquitination pathway, thereby allowing activation of the NF-kB. AbstractPemphigus vulgaris is a rare chronic blistering skin disease resulting from IgG autoantibodies directed against transmembrane desmosomal glycoprotein desmoglein 3 and is the most common form of pemphigus. Since interleukin-1 receptor-associated kinase (IRAK-1)/nuclear factor-kappa B (NF-kappa B) pathway plays an essential role in the pathogenesis of autoimmune diseases, the aim of the present study was to explore the role of polymorphisms in three genes, named IRAK1 (rs3027898), NFKBIA (rs696) and NFKB1 (-94ATTG insertion/deletion variant, -rs28362491), in PV susceptibility. Forty-four unrelated patients with PV (23 males) were enrolled in the study.Additionally, 77 ethnic matching healthy volunteers (45 males) with no personal or family history of chronic autoimmune or infectious diseases were studied. Strong statistical significant difference was observed between PV patients and controls for polymorphism -94 insertion/deletion ATTG in the promoter region of NFKB1 gene (P = 0.00005). Additional dedicated studies in larger groups of patients of various ethnicities are needed to replicate and confirm the preliminary findings. K E Y W O R D S IRAK1, NFKB1, NFKBIA, pemphigus vulgaris, polymorphism | 973 CHATZIKYRIAKIDOU eT Al. P-value 0.33353 0.00005 0.2844 Alleles Alleles Alleles C A Ins Del G A Male PV patients (n = 23) 5 18 PV patients (n = 88) 63 25 45 43 Male Controls (n = 45) 17 28 Controls (n = 154) 75 79 86 68 P-value 0.186 P-value 0.0006 0.480 OR, 95% CI 0.476 (0.144-1.459) OR, 95% CI 2.65 (1.515-4.651) 0.828 (0.489-1.399) Genotypes CC AC AA Female PV patients (n = 21) 1 11 9 Female Controls (n = 32) 2 15 15 P-value (Yates' correction) 0.932 The authors have declared no conflicting interests. AUTH O R CO NTR I B UTI O N AC had the concept and designed the study, performed the rese...

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