***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: We studied the clinical and immunological effects of Rituximab ( anti-CD20 ) therapy in patients with lupus nephritis . In an open clinical trial , 22 patients with active systemic lupus erythematosis and renal involvement ( mainly class III and IV according to the WHO classification ) that was refractory to conventional therapy were studied . In all these patients , Rituximab ( 0.5 to 1.0 g at days 1 and 15 ) was added to the immunosuppressive therapy and its therapeutic effect was evaluated . In addition , the levels and function of regulatory T lymphocytes and the apoptosis of immune cells were assessed . We found a significant reduction in disease activity ( p < 0.05 , MEX-SLEDAI index ) , and proteinuria ( p < 0.05 ) at days 60 and 90 of Rituximab therapy . Although most patients showed improvement in creatinine clearance and erythrocyturia , no significant changes in these parameters were detected . In most patients ( 20/22 ) , B cell depletion was observed , but no clear-cut effect of Rituximab on complement levels or auto-antibody titers was detected ( p > 0.05 in all cases ) . One patient died at day 70 with invasive histoplasmosis . No important adverse effects of Rituximab therapy were registered in other patients . A significant enhancement in the levels of different CD4 + regulatory cells ( TREG , Th3 , Tr1 ) , but not CD8 + Ts lymphocytes , was observed at day 30 . This increase was sustained for TREG cells at day 90 , and accompanied by an improvement in their regulatory function . In addition , we observed an unexpected increase in the apoptosis of T cells at day 30 . Interestingly , the enhancement in the suppressive function of TREG cells was not observed in the two patients that showed the poorest clinical response to Rituximab . We conclude that the data obtained in this open clinical trial suggest that Rituximab is a promising c and i date for r and omized controlled trials in patients with lupus nephritis refractory to the conventional immunosuppressive therapy . The effects of Rituximab on regulatory cells and apoptosis of T lymphocytes are interesting and its possible role in the putative effect of this biological agent in systemic lupus erythematosis deserves additional studies Objective : To study the effects in systemic lupus erythaematosus ( SLE ) of B cell directed therapy with rituximab , a chimeric monoclonal antibody directed at CD20 + B cells , without concomitant immunosuppressive therapy in mild to moderate SLE . Methods : Patients ( n = 24 ) with active SLE and failure of ⩾1 immunosuppressive were recruited from three university centres into this phase I/II prospect i ve open-label study . Patients were followed for 1 year to assess safety , efficacy and biological effects . Results : In total , 18 of the patients scheduled to receive the full lymphoma dose of rituximab  were evaluable for B cell levels in peripheral blood . Of these , 17 had effective CD19 + B cell depletion ( < 5 cells/μl ) . However , six of the depleted patients showed B cell return before 24 weeks . A total of 70 % of patients improved by week 55 , as defined by an SLE Disease Activity Index ( SLEDAI ) score improvement of ⩾2 units from baseline . The degree of CD19 + B cell depletion was correlated with SLEDAI improvement at week 15 ( r = 0.84 ) . In general , rituximab infusions were well tolerated . Approximately a third of the patients developed human anti-chimeric antibody ( HACA ) titres , which correlated with poor B cell depletion . Most patients ( 9 of 14 ) did not respond to immunisations with Pneumovax and tetanus toxoid . Conclusions : Rituximab is a promising new therapy for SLE . The variability of responses in patients with SLE may be related to HACA formation . The failure to respond to immunisations is surprising , in view of the apparently low risk of infections . Better biological markers are necessary to follow these patients during treatment OBJECTIVE Autoreactive B cells play a key role in tissue injury in systemic autoimmune disease , and therefore a treatment result ing in B cell depletion could have benefit . This open-label study was undertaken to evaluate the efficacy of the anti-CD20 monoclonal antibody rituximab in the treatment of lupus nephritis . METHODS Lupus patients with active proliferative nephritis ( 4 with focal disease and 6 with diffuse disease ) received rituximab ( 4 weekly infusions of 375 mg/m(2 ) ) combined with oral prednisolone . Clinical , laboratory , and immunologic responses , including peripheral lymphocyte subsets measured by flow cytometry , were prospect ively assessed at monthly intervals for 12 months . Complete remission of nephritis was defined as normal serum creatinine and albumin levels , inactive urine sediment , and 24-hour urinary protein < 500 mg . Partial remission was defined as > 50 % improvement in all renal parameters that were abnormal at baseline . RESULTS B cell depletion lasted from 1 month to 7 months and was well tolerated . Partial remission was achieved in 8 of 10 patients within a median of 2 months ( range 1 - 4 months ) ; in 5 of them , complete remission was subsequently established ( at a median of 3 months from baseline ) , and it was sustained at 12 months in 4 . As early as 1 month from baseline , the expression of the costimulatory molecule CD40 lig and on CD4 + T cells was decreased by 4-fold , and it was almost blocked when partial remission was clinical ly evident . The expression of T cell activation markers CD69 and HLA-DR was significantly decreased at time points when partial remission was observed , and was further decreased during complete remission . In contrast , in patients who did not exhibit a response or when relapse was detected in patients in whom an initial remission had been achieved , such decreases were not prominent . Serum concentrations of double-str and ed DNA autoantibodies were decreased in all patients , regardless of clinical outcome . CONCLUSION Following B cell depletion , clinical remission of lupus nephritis is associated with a decrease in T helper cell activation , suggesting an additional role for B cells , independent of autoantibody production , in promoting disease . A controlled trial to confirm these promising clinical results is warranted OBJECTIVE B cells are likely to contribute to the pathogenesis of systemic lupus erythematosus ( SLE ) , and rituximab induces depletion of B cells . The Exploratory Phase II/III SLE Evaluation of Rituximab ( EXPLORER ) trial tested the efficacy and safety of rituximab versus placebo in patients with moderately-to-severely active extrarenal SLE . METHODS Patients entered with > or=1 British Isles Lupus Assessment Group ( BILAG ) A score or > or=2 BILAG B scores despite background immunosuppressant therapy , which was continued during the trial . Prednisone was added and subsequently tapered . Patients were r and omized at a ratio of 2:1 to receive rituximab ( 1,000 mg ) or placebo on days 1 , 15 , 168 , and 182 . RESULTS In the intent-to-treat analysis of 257 patients , background treatment was evenly distributed among azathioprine , mycophenolate mofetil , and methotrexate . Fifty-three percent of the patients had > or=1 BILAG A score at entry , and 57 % of the patients were categorized as being steroid dependent . No differences were observed between placebo and rituximab in the primary and secondary efficacy end points , including the BILAG-defined response , in terms of both area under the curve and l and mark analyses . A beneficial effect of rituximab on the primary end point was observed in the African American and Hispanic subgroups . Safety and tolerability were similar in patients receiving placebo and those receiving rituximab . CONCLUSION The EXPLORER trial enrolled patients with moderately-to-severely active SLE and used aggressive background treatment and sensitive cutoffs for nonresponse . No differences were noted between placebo and rituximab in the primary and secondary end points . Further evaluation of patient subsets , biomarkers , and exploratory outcome models may improve the design of future SLE clinical trials Although corticosteroids and immunosuppressants are widely used for the treatments of systemic lupus erythematosus ( SLE ) , safer and more effective therapies are prerequisite . We and others have reported that anti-CD20 antibody rituximab targeting B cells are effective for refractory SLE and , therefore , safety and clinical efficacy of rituximab in SLE was evaluated by a multicenter phase I/II clinical trial . An open-label , multicenter study of 15 patients with active and refractory SLE ( total British Isles Lupus Assessment Group [ BILAG ] score 8 to 17 ) was conducted .  Rituximab was administered to 5 SLE patients as 4 infusions of 500 mg/body every week and to 10 SLE patients as 2 infusions of 1000 mg/body every other week . Assessment of safety , infusion reactions and adverse effects was used as the primary outcome for clinical tolerability and was evaluated by 28 weeks . Rituximab was well tolerated , with most experiencing no significant adverse effects . B cells rapidly reduced in all patients and remained low until 6 months post-treatment . Four patients developed human antichimeric antibodies without affecting efficacy of rituximab . Changes in routine safety laboratory tests clearly related to rituximab were not observed . Nine among 14 evaluable patients achieved the major or partial clinical response of BILAG score and prednisolone dose significantly decreased at the 28 weeks . Rituximab therapy appears to be safe for the treatment of active SLE patients and holds significant therapeutic promise , at least for the majority of patients experiencing profound B-cell depletion OBJECTIVES To assess the clinical and basic serological consequences of B-cell depletion with rituximab in the treatment of patients with systemic lupus erythematosus ( SLE ) who have failed conventional immunosuppression . METHODS An open study of 24 patients with severe SLE followed for a minimum of 3 months is reported . In the majority of patients ( 19 out of 24 ) , 6 months follow-up data are described . Disease activity in these patients was assessed every 1 - 2 months using the British Isles Lupus Assessment Group ( BILAG ) system and estimates of anti-double-str and ed DNA antibodies and serum C3 levels . During the follow-up period , significant side-effects were sought and the reduction in oral prednisolone was recorded . It was our general practice to stop concomitant immunosuppression ( e.g. azathioprine , mycophenolate ) when B-cell depletion was given ( in most cases in the form of two 1 g intravenous infusions of rituximab 2 weeks apart accompanied by two 750 mg intravenous cyclophosphamide infusions and two methylprednisolone infusions of 250 mg each ) . RESULTS Twenty-two patients were female and two male . At the time of B-cell depletion , the mean age was 28.9 yr ( range 17 - 49 ) and the mean disease duration was 7.9 yr ( range 1 - 18 ) . The global BILAG score ( P < 0.00001 ) , serum C3 ( P < 0.0005 ) and double-str and ed DNA binding ( P < 0.002 ) all improved from the time of B-cell depletion to 6 months after this treatment . Only one patient failed to achieve B-lymphocyte depletion in the peripheral blood . The period of B-lymphocyte depletion ranged from 3 to 8 months except for one patient who remains depleted at more than 4 yr . Analysis of the regular BILAG assessment s showed that improvements occurred in each of the eight organs or systems . The mean daily prednisolone dose fell from 13.8 mg ( s.d . 11.3 ) to 10 mg ( s.d . 3.1 ) . CONCLUSION In this open study of patients who had failed conventional immunosuppressive therapy , considerable utility in the use of B-cell depletion has been demonstrated . Our data provide strong support for the performance of a full double-blind control trial Introduction The purpose of this observational study was to analyze the rates , characteristics and associated risk factors of severe infections in patients with systemic autoimmune diseases ( SAD ) who were treated off-label with biological agents in daily practice . Methods The BIOGEAS registry is an ongoing Spanish prospect i ve cohort study investigating the long-term safety and efficacy of the off-label use of biological agents in adult patients with severe , refractory SAD . Severe infections were defined according to previous studies as those that required intravenous treatment or that led to hospitalization or death . Patients contributed person-years of follow-up for the period in which they were treated with biological agents . Results A total of 344 patients with SAD treated with biological agents off-label were included in the Registry until July 2010 . The first biological therapies included rituximab in 264 ( 77 % ) patients , infliximab in 37 ( 11 % ) , etanercept in 21 ( 6 % ) , adalimumab in 19 ( 5 % ) , and ' other ' agents in 3 ( 1 % 
    Output:
    
Acceptable evidence suggested improvements in disease activity , arthritis , thrombocytopaenia , complement and anti-dsDNA , with a steroid-sparing effect .
But relapses of disease were demonstrated too .
Weak evidence suggested a response in anaemia , cutaneous and neuropsychiatric manifestations .
Available evidence revealed few major adverse events .
Rituximab has been shown to be safe and effective in the treatment of non-renal SLE , especially in terms of disease activity , immunologic parameters and steroid-sparing effect .
However , it can only be recommended for organ-specific manifestations such as arthritis and thrombocytopaenia .