New approaches of B-cell-directed therapy: beyond rituximab.
OBJECTIVE
This study reviews therapeutic approaches of direct and indirect B-cell targeting in autoimmune diseases and their impact on protective immunity.


RESULTS
Beyond recent clinical experiences with rituximab as B-cell-depleting agent, other biologicals targeting CD20, such as ocrelizumab, ofatumumab, hA20, and TRU-015 mainly deplete B cells and are under clinical investigation in different entities. Moreover, anti-CD22 targeting as another approach that has been studied in clinical trials showed a modest depletion, but inhibition of B-cell activation. More indirect innovative B-cell-affecting therapies comprise blockade of cytokines, such as B-cell-activating factor (BAFF/BLyS), APRIL, and their receptors as well as blockade of costimulation. Although decreases of immunoglobulin levels were seen, so far no major increases in infections were reported.


CONCLUSIONS
The value of certain B-cell-depletion therapies as well as other therapies modulating B-cell functions needs to be further delineated, especially in the therapeutic regimen of rheumatoid arthritis, specific collagen vascular diseases and vasculitis. Long-term observations of protective immunity are also needed to further evaluate the rate of infections.
Dörner
Thomas
T
Charite Center 14, Charite University Hospital Berlin, Berlin, Germany. thomas.doerner@charite.de
Burmester
Gerd R
GR
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D013601:T-Lymphocytes / Q000187:drug effects
D000911:Antibodies, Monoclonal; D007155:Immunologic Factors