b cells occupy a central role in normal immunity . they interact with antigen - presenting cells , act as antigen - presenting cells themselves , provide co - stimulatory support to t cells , differ from plasma cells and produce antibodies . as expected , abnormal b cell function plays a major role in immune dysregulation such as autoimmunity . abnormal b and t cell interactions may be amplified by t cell - derived cytokines such as the b lymphocyte stimulator and a proliferation - inducing ligand . additionally , b cells have been found in affected tissues from nasal biopsies of patients with anca - associated vasculitis ( aasv )   or from renal biopsies of patients with membranous nephropathy . b cell - directed therapies include those that deplete b cells and those that alter b cell function . b cell depletion can be achieved by using monoclonal antibodies against b cell - specific antigens such as cd20 , cd19 and cd22 . b cell modulation comprises the blockade of the following cytokines : b cell - activating factor / b lymphocyte stimulator , proliferation - inducing ligand and their receptors , as well as co - stimulation blockade . rituximab is a mouse / human igg1k chimeric monoclonal antibody against the cd20 cell surface receptor of the b cell . cd20 is expressed on immature , mature and activated b cells but not on long - lived plasma cells . rituximab depletes b cells by three mechanisms : antibody - dependent cell - mediated cytotoxicity , complement - dependent cytotoxicity and apoptosis . one course of rituximab effectively depletes b cells for 6 - 9 months in over 80% of the patients . rituximab has first been licensed for the treatment of non - hodgkin 's lymphoma in the 1990s and has been approved for the treatment of rheumatoid arthritis in 2006 . thereafter , it has been used increasingly in autoimmune diseases . at first , the standard dosing regimens were either the so - called lymphoma protocol ( four weekly doses of 375 mg / m ) or the rheumatoid arthritis protocol ( two doses of 1 g , 2 weeks apart ) . with growing evidence of its use , many adaptations have been made , including modified shorter courses or prolongation of treatment at fixed - dose intervals . according to the literature , up to 8% of all lymphoma patients experience a delayed neutropenia that may be profound but finally resolves . true estimates about the incidence of infections after rituximab treatment are difficult because most patients receive concomitant immunosuppression . rituximab use is not associated with an increased risk neither for common nor for opportunistic infections . , no definite conclusion can be drawn , since such patients also received intensive immunosuppression . on the other hand , the syndrome occurred also in patients who had never received rituximab . since rituximab does not deplete long - lived plasma cells , there is no decrease in immunoglobulin levels . they may shorten the time of effective b cell depletion , but the true incidence and importance of these antibodies are unknown . specifically in idiopathic glomerulonephritides , most of the available data concern the use of rituximab in idiopathic membranous nephropathy ( imn ) and steroid - resistant nephrotic syndrome ( ns ) . secondary forms of glomerulonephritis include systemic lupus erythematosus ( sle ) and aasv . in renal transplantation , rituximab has been used for the desensitization of highly sensitized patients before transplantation and as part of the preconditioning of the recipient before abo - incompatible transplantations . furthermore , it is used in severe immune - mediated , antibody - associated rejection . since imn is characterized by autoantibody formation and immune complex deposition , from the pathogenetic point of view , the use of rituximab is reasonable . were the first who used rituximab as first - line therapy in 8 patients with imn . in the meantime , several case series and small prospective trials reporting that rituximab is efficacious in imn have been published . a meta - analysis published in 2009   summarized the results of rituximab use in 85 patients with imn . it showed good remission rates ( 15 - 20% had complete and 35 - 40% had partial remission ) and excellent tolerance . our experience with 12 imn patients who were treated with rituximab was sustained remission in 11 of these patients during a median follow - up of 48 months . a comparison of the two main dosing regimens of rituximab for imn therapy showed equal efficacy . an interesting study by ruggenenti et al .   evaluated the effect of rituximab on the morphofunctional abnormalities of imn . after induction of remission , there was reabsorption of the subepithelial dense deposits in repeat biopsies , which strongly suggested interference of rituximab with the pathogenetic mechanism . in most reports , the drug was used as a first - line treatment . despite its excellent tolerability and the good efficacy data , rituximab is not licensed for the treatment of membranous nephropathy , since data from randomized controlled trials are missing . most of the literature comes from pediatric experience because pediatricians are most often confronted with this disease , either in the form of steroid dependency and frequent relapses or as steroid - resistant ns . a study on 70 children treated with rituximab reported a response rate of 82% in steroid - dependent ns , 44% in steroid - resistant ns and 60% in recurrent posttransplant ns . another report on 57 patients showed sustained remission in 83% of the steroid - dependent ns cases and in 21% of the steroid - resistant ns cases at 12 months . both reports showed good results in cases in which rituximab was used as rescue therapy . nevertheless , questions about how early or late rituximab should be administered , the duration of remission and the indications for retreatment are still open . conventional immunosuppression has changed the fatal course of primary systemic aasv to a chronic disease with remission periods and relapses . however , therapy - related toxicity ( especially infections ) , primary treatment failures in up to 20% and a relapse rate of > 50% at 5 years together with a persistently high mortality rate reflect the unmet needs in the standard of care of these patients . the therapeutic limitations of standard immunosuppression and the accumulating evidence of the importance of anca in the pathogenesis of this disease constitute the rationale for rituximab use in aasv . from the standpoint of efficacy , rituximab is effective in aasv . in small case series and open - label trials , a clinical response occurred in the majority of patients , with the exception of those with refractory granulomatous manifestations . recently , two randomized trials using rituximab as induction therapy in aasv have been published . in the european rituxvas trial , 44 patients were randomly assigned to receive corticosteroids plus either rituximab or cyclophosphamide as induction therapy for aasv with severe renal involvement . after 12 months , there was no difference , neither in remission rates ( 76 vs. 82% , p = 0.68 ) nor in the serious adverse event rates ( 42 vs. 36% ) . the rave - itn trial , conducted in the usa , is a noninferiority trial directly comparing rituximab to oral cyclophosphamide as induction therapy in 197 patients with severe but not life - threatening aasv . rituximab was not inferior to cyclophosphamide for induction of remission at 6 months and it even showed superiority in patients with frequent relapses . adverse event rates , however , were comparable . in both trials , rituximab showed no superiority in terms of safety , but both were short - term trials and therefore not designed to detect possible advantages of cyclophosphamide avoidance translating into lower long - term mortality . regarding rituximab use as maintenance therapy , although encouraging , there are no conclusive data about medium- and long - term efficacy and safety . open - label trials with multiple dosing regimens have been conducted . to our knowledge , the only randomized trial that evaluated rituximab for maintenance of remission is the rave - itn trial . induction therapy with rituximab was followed by placebo , whereas cyclophosphamide therapy was followed by azathioprine after 3 - 6 months . a single course of rituximab was as effective as conventional therapeutic regimens in remission maintenance at 12 and 18 months . especially in frequently relapsing disease , rituximab continued to be superior to conventional immunosuppression at 12 months but not at 18 months when b cells had reappeared . the relapse rates did not differ significantly between the two groups ( 32 vs. 29% ) . the safety of the two therapeutic regimens was similar , as was patient survival during the 18 months of follow - up . questions about the treatment of relapses preemptively or after the relapse and about the use of rituximab at fixed - dose intervals or with and without the concomitant use of steroids are still open . nevertheless , rituximab seems to be a promising way to avoid long - term toxicity without losing the high - efficacy benefit that is gained with cytotoxic drugs . sle is the prototypic autoimmune disease , with a variety of autoantibodies directed against diverse cellular components and multiorgan involvement . since b cells are a key component of the dysregulated autoimmune response , there is a rationale for the wide use of b cell - depleting agents in this disease . regarding sle nephritis , rituximab has been used as induction therapy in refractory cases or in conjunction with low - dose conventional immunosuppression . cumulative evidence from small , open - label trials suggests that rituximab is both safe and effective in lupus nephritis . a multicenter phase iii trial   of rituximab versus placebo given as induction therapy in addition to mycophenolate mofetil ( mmf ) and high - dose steroids in both treatment arms did not attain its primary end point ( renal response ) in 144 sle nephritis patients at 52 weeks . one explanation for favoring rituximab seems logical : the trial was intended to detect a large clinical effect in patients with very active disease . this was not possible for a biological agent given in addition to high - dose conventional therapy in both treatment arms . further studies using rituximab in targeted populations are needed . for the use of rituximab as maintenance therapy , data from small , uncontrolled studies showed that sustained b cell depletion with repeated courses of rituximab either in conjunction with low doses of mmf / steroids or as monotherapy is effective and helps avoid long - term cyclophosphamide toxicity . from our experience , the addition of rituximab to mmf is effective for the treatment of relapsing proliferative lupus nephritis . recent recommendations suggest the use of rituximab either in addition to mycophenolic acid or to cyclophosphamide in refractory cases of proliferative lupus nephritis . over the past 2 decades , immunosuppressive strategies in kidney transplantation have focused on targeting t cells . however , there is increasing interest in the role of b cells , plasma cells and autoantibodies in transplantation . the use of rituximab first emerged after its use in abo - incompatible renal transplantation , where it successfully replaced the more invasive splenectomy as part of the recipient - preconditioning protocol . its use in acute antibody - mediated rejection , in mixed cellular and humoral as well as cellular rejection resistant to t cell therapies amounts to a total of 150 patients . the role of anti - cd20 remains to be better determined . from the pathogenetic point of view , it effectively depletes circulating and intragraft - nave b cells , plasmablasts and short - lived plasma cells but not long - lived , antibody - producing plasma cells , and it mainly acts via inhibition of t cell activation and by preventing the generation of new , alloantibody - producing b cells after repopulation . from the clinical point of view , it seems partially effective in resolving acute antibody - mediated rejection , but always in conjunction with other therapies such as iv immunoglobulin and/or plasmapheresis . anti - cd20 does not seem to be effective in chronic antibody - mediated rejection , where newer , plasma cell - depleting agents such as the proteasome inhibitor bortezomib show greater benefit . one major concern about the use of b cell - depleting agents in transplantation is that they also have inhibitory capacity , thereby prohibiting the induction of tolerance . future studies on b cell depletion should provide more insight into the role and interplay of the different b cell subsets before and after depletion and use combinations of newer agents to achieve not only depletion but more sophisticated b cell modulation .
b cells play a central role in the pathogenesis of many autoimmune diseases . 
 selective targeting can be achieved with the use of the monoclonal antibody rituximab . 
 in addition to being a drug for non - hodgkin 's lymphoma , rituximab is also an fda - approved treatment for refractory rheumatoid arthritis and , since recently , anca vasculitis . 
 it has shown efficacy in many autoimmune diseases . 
 this review will discuss current evidence and the rationale of the use of rituximab in glomerular diseases , including randomized controlled trials . 
 the focus will be on the use of rituximab in idiopathic membranous nephropathy , systemic lupus erythematosus and anca - associated vasculitis . 
 the emerging role of rituximab in renal transplantation , where it seems to be important for the desensitization protocols for highly sensitized patients as well as for the preconditioning of abo - incompatible recipients and the treatment of antibody - mediated rejection , will also be addressed .