**1. Introduction**

254 Autoimmune Disorders – Current Concepts and Advances from Bedside to Mechanistic Insights

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complexity in mice reconstituted with human immunoglobulin yeast artificial

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by B cell hyperactivity and defective T-cell function, with production of high titer autoantibodies and clinical involvement in multiple organ systems. Patients with mild SLE can generally be maintained on a combination of non-steroidal anti-inflammatory drugs and antimalarials. Corticosteroids, azathioprine and cyclophosphamide remain important for long term management of most patients with active disease and even those in clinical remission. However, these agents have considerable side effects and are not effective in all patients with SLE. Novel immunological therapies include both B and T cell directed treatments, anticytokine and complement directed therapies. These modalities enable more specific immunosuppression, and include cyclosporin, high-dose intravenous immunoglobulin, mycophenolate mofetil, tacrolimus and new purine nucleoside analogs (Schröder and Zeunerorts 2009).

In recent years, clinical studies have been undertaken with selected monoclonal antibodies (mAbs) in the treatment of several hematological diseases, especially in malignant disorders. However, some clinical observations indicate that mAbs may be an important alternative for the conventional therapy of some autoimmune disorders (Robak 2004).

B-lymphocytes are an essential component of the acquired immune response (La Cava 2010). They randomly express cell-surface receptors which are often autoreactive and must be controlled by the process of B-cell tolerance. In SLE, the number of B-cells in the peripheral blood is often decreased, and those that are present have abnormal phenotypes indicative of activation. The important role of B cells in the pathogenesis of SLE has provided a strong rationale to target B cells in SLE. Selective therapeutic depletion of B-cells became possible with the availability of the anti-CD20 antibody rituximab.
