Explain the relationship between HLA-DRB1*04, smoking, the expression of peptidyl arginine deaminase, and rheumatoid arthritis
What will be an ideal response?
Peptidyl arginine deaminase (PAD) is an enzyme induced in the respiratory tract after smoke-induced damage. PAD converts arginine residues in self proteins to citrulline residues, thus creating epitopes to which the T-cell repertoire is not tolerant. Citrullinated proteins are subject to proteolysis, and the resulting peptides bind to HLA-DRB1*04 and stimulate autoreactive CD4 T cells and antibodies against citrullinated self proteins. If a joint becomes infected or is wounded, inflammation of joint tissue activates PAD, which generates the same citrullinated epitopes. HLA-DRB1*04-restricted effector and memory T cells are recruited and activated and an immune response follows, initiating the development of rheumatoid arthritis.
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