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Ankylosing spondylitis, psoriasis, and Behcet's disease are seronegative genetically complex diseases that are also considered complex autoinflammatory diseases. These diseases are characterized by strong association of class I human leukocyte antigen (HLA) alleles and also have a strong contribution to disease-risk by variants of the endoplasmic reticulum-associated amino-peptidase 1 (ERAP1) gene that is limited to individuals who carry the disease-specific HLA class I allele. The ERAP1 protein is responsible for trimming peptides for loading onto HLA class I molecules, which are displayed on the surface of nearly all cells, where they play important roles in immune surveillance and in innate and adaptive immune functions. ERAP1 is highly polymorphic with several SNPs encoding variant amino acids that are likely to influence the nature of peptides bound as well as their ability to be trimmed. These non-synonymous coding variants are not found in isolation, but in combinations or allotypes that act in concert to influence the peptidome available for HLA binding and presentation.

Identification of ERAP1 protein allotypes in the Turkish population and evaluation of their contributions to Behçet's disease risk