The role of the PD-1 protein in pathogenesis of autoimmune diseases, with particular consideration of rheumatoid arthritis and systemic lupus erythematosus

• Main Authors: Anna Siwiec, Maria Majdan
• Format: Article
• Language: English
• Published: Index Copernicus International S.A. 2015-04-01
• Series: Postępy Higieny i Medycyny Doświadczalnej
• Subjects: PD-1 protein; Autoimmune Diseases; systemic lupus erythematosus; rheumatoid arthritis; pathogenesis; Genetics
• Online Access: http://phmd.pl/gicid/01.3001.0009.6528
• ISSN: 0032-5449; 1732-2693

Polymorphism of the PDCD1 gene for the PD-1 protein (programmed cell death 1, encoded by PDCD1) is significantly associated with higher incidence of autoimmune diseases, such as rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE), which may suggest the participation of PD-1 in the pathogenesis of these diseases. Over 30 single nucleotide polymorphisms (SNPs) have been identified in the human PDCD1 gene. SNPs in the PDCD1 gene in humans have demonstrated relevant associations with a higher risk of developing autoimmune diseases in certain ethnic groups. RA and SLE are chronic connective tissue diseases with autoimmune background. RA is a common form of chronic, progressive arthritis in adults. SLE is characterized by chronic inflammation in most of the body’s tissues and organs, leading to a complex clinical syndrome. The pathogenesis of the autoimmune diseases is not well examined. However, genetic factors, immunological disorders and environmental factors are believed to play a decisive role in the occurrence of the illnesses. Complex immune system disorders are responsible for the development of SLE. In RA activated T cells produce cytokines such as interleukin 2 (IL-2) and interferon γ (IFN-γ) that stimulate macrophages and monocytes. The main role of PD-1 is inhibition of T-cell proliferation, inhibition of production of IL-2, interleukin 10 (IL-10) and IFN-γ, and inhibition of activation of autoreactive lymphocytes. Because of the wide range of ligand distribution in the body, the biological significance of protein refers to almost all aspects of the immune response, including autoimmunology, tumour immunology, inflammation, transplantation, and allergy. Currently, there is increasing interest in the importance of PD-1 in the maintenance of immunological balance and its role in the development of autoimmune diseases. We summarize the PD-1 research in patients with RA and SLE in recent years.