| Zdroj: |
Karrar, S & Cunninghame Graham, D S 2018, ' Review: Abnormal B Cell Development in Systemic Lupus Erythematosus : What the Genetics Tell Us ', Arthritis and Rheumatology, vol. 70, no. 4, pp. 496-507 . https://doi.org/10.1002/art.40396 |
| Popis: |
Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell dysfunction, production of autoantibodies directed toward cellular and nuclear components, and multiorgan damage caused by immune complex deposition and inflammation within affected tissues 1. It largely affects women of childbearing age (the third and fourth decades of life) and is associated with significant morbidity and mortality.In healthy individuals, B cells with autoreactive receptors are selected out during B cell maturation, starting at the initial stages of B cell receptor (BCR) development in the bone marrow and continuing through to the fine tuning that occurs in activated mature B cells in secondary lymphoid tissue. Studies in lupus patients as well as mouse models indicate that these processes are altered in SLE.The etiology of the disease is complex and its phenotype is highly heterogeneous, but genetic susceptibility is thought to contribute as much as 60% of disease risk 2. Although rare monogenic causes do exist, heredity in SLE is complex, with multiple common variants contributing to disease, with patients having to achieve a certain “genetic threshold” for disease risk. This genetic risk, in combination with environmental factors (exposure to ultraviolet sunlight, smoking, and infections including Epstein‐Barr virus have all been implicated), leads to development of the disease 1. In this review, we summarize some of the B cell anomalies in SLE and incorporate evidence from studies in humans and mouse models, together with data from genetic association studies, to explain the mechanisms behind B cell dysregulation in SLE. |
