**8. Conclusions**

In recent years, clinical studies have been undertaken with selected mAbs in the treatment of SLE. The most frequently used mAb is rituximab, which is directed against CD20, a membrane protein expressed on B lymphocytes. Rituximab is effective in depleting B cells from peripheral blood, lymph nodes and bone marrow. Recent clinical studies confirm the high activity of rituximab in SLE patients, especially with lupus nephritis and neuropsychiatric involvement. Rituximab was generally well tolerated. However, occasionaly serious infections were reported. Over the last few years new generations of anti-CD20 mAbs have been developed for potential benefits over rituximab. They were engineered to have augmented antitumor activity by increasing CDC or ADCC activity and increased Fc binding affinity for the low-affinity variants of the FcγRIIIa receptor (CD16) on immune effector cells. This mAbs are are highly cytotoxic against B-cell lymphoid cells and are now being evaluated in clinical trials.

More recently, several newer mAbs have been developed and are being evaluated in phase I/II clinical trials. These include anti-cytokine therapies anti-CD40L mAbs, anti-CD-22 mAb, anti-BLys mAbs and anti- C5 mAbs. Belimumab is a fully human monoclonal antibody that binds to BLyS and inhibits its biological activity. Significantly positive results in both phase 3 studies have raised hopes that belimumab may be the long-awaited new effective therapy for SLE. Proinflammatory cytokines such as tumor necrosis factor (TNF) and interleukin- 6 (IL-6) play an important role in propagating the inflammatory process responsible for tissue damage. Blocking of these cytokines by mAbs can be also a successful therapy for patients with SLE. Finally, mAb eculizumab that specifically inhibits terminal complement activation has been recently developed and investigated in a phase I single dose study in SLE. These potentially useful agents should be further evaluated in well designed controlled trials.
