Medical genetics Human leukocyte antigens class I and class II in patients with pemphigus in southern Turkey Cilem Kaya Koc 1 , MD, Nilgun Sallakci 2 , MSc, Ays ¸ e Akman-Karakas ¸ 1 , MD, Erkan Alpsoy 1 , MD and Olcay Yegin 2 , MD Departments of 1 Dermatology and Venereology, and 2 Pediatric Immunology, Akdeniz University School of Medicine, Antalya, Turkey Correspondence Erkan Alpsoy, MD Department of Dermatology and Venereology Akdeniz University School of Medicine 07059 Antalya Turkey E-mail: ealpsoy@akdeniz.edu.tr Funding: This study was supported by the Akdeniz University Scientific Research Projects Unit. Conflicts of interest: None. This study was presented at the 18th Congress of the European Academy of Dermatology and Venereology, October 7–11, 2009, Berlin. Abstract Background Genetic factors that predispose individuals to pemphigus are considered to play important roles in the development of the disease. Furthermore, population studies of patients with pemphigus have clearly shown that the most prevalent alleles differ across ethnic groups. Objectives This controlled study was designed to detect the distribution of human leuko- cyte antigen (HLA) class I and II alleles in Turkish patients with pemphigus. Methods Sixty patients diagnosed with pemphigus according to clinical findings, histology, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were enrolled in the study. The control group consisted of 60 healthy adult transplant donors. HLA typing was carried out using a polymerase chain reaction (PCR) with sequence-specific primers (SSP) method. Results The frequencies of HLAs A*11, CW*01, DRB1*04, DRB1*14, DQB1*05, and DPB1*0401 were found to be statistically significantly higher in the disease group than in controls. By contrast, the frequencies of HLAs B*18, B*50, DRB1*11, DQB1*02, DQB1*06, DPB1*0301, and DPB1*1102 were statistically significantly lower in the pemphigus group than in controls. Linkage dysequilibrium analysis showed that DRB1*14/DQB1*05, A*11/ DQB1*05, and A*11/DRB1*14 alleles were detected frequently in pemphigus patients, and DRB1*11/DQB1*05, DRB1*14/DQB1*02, B*50/DQB1*02, and B*50/DPB1*0301 alleles appeared frequently in healthy controls. Conclusions The results suggest that DRB1*04, DRB1*14, DQB1*05, and DPB1*0401 class II HLAs and A*11 and CW*01 class I HLAs are associated with pemphigus in south- ern Turkey. Observed differences in LD patterns between patients and controls suggest that the coexistence of the respective alleles is strongly determinant of predisposition towards (DRB1*14/DQB1*05 and A*11/DQB1*05) or protection against (B*50/DQB1*02) the disease. Introduction Pemphigus is a life-threatening, autoimmune, blistering disease of the skin and mucous membranes. 1 Pemphigus vulgaris (PV) can develop at any age but is most com- monly diagnosed in the fourth to sixth decades of life. Annual incidences of pemphigus reported from different regions of the world range from 0.08 to 2.72 per 100,000 population. 2,3 Although the disease can affect anyone, it is most prevalent in people of Mediterranean or Jewish ancestry. 1–4 Our previous study 2 showed pemphigus to be the most common autoimmune bullous disease in the Mediterranean region of Turkey. The mean annual inci- dence in the population aged >20 years was 0.40 per 100,000 population. 2 Interactions among genetic and environmental factors are important in the etiopathogenesis of pemphigus. 4 Genetic factors that predispose individuals to pemphigus are considered to play important roles in the development of the disease. 5–11 As in all organ-specific autoimmune diseases, tolerance breakage to target autoantigens is thought, although not exclusively, to take place at the T cell level (i.e. at the immunological synapse involving human leukocyte antigen [HLA] class I or II molecules, the initiating autoantigenic peptides and T cell receptors [TCRs]). The genes coding for the TCR, major histocom- patibility complex (MHC), and desmogleins (dsg) should also be considered as candidate genes conferring suscepti- bility. 12,13 Specific HLA alleles are considered as predom- inant predisposing genetic factors. The disease generally 53 ª 2013 The International Society of Dermatology International Journal of Dermatology 2013, 52, 53–58