Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterised by B-cell dysfunction, production of autoantibodies directed towards cellular and nuclear components and tissue damage caused by immune complex deposition and inflammation. It largely affects women in the 3rd and 4th decades of life and is associated with significant morbidity and mortality. In healthy individuals, B-cells with auto-reactive receptors are selected out during B-cell maturation, starting at the initial stages of B-cell receptor development in the bone marrow, 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 aetiology of the disease is complex and phenotype highly varied, but genetic susceptibility is thought to contribute as much as 60% of disease risk. 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 UV sunlight, smoking and infections including EBV have all been implicated), leads to the development of the disease. In Dec 5, 2017, Sarah Karrar and others published an article in << Arthritis & Rheumatology >> which title is “Abnormal B-cell development in Systemic Lupus Erythematosus: what the genetics tell us”. In this review, they summarise 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.
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