B-cell Repopulation Research Articles

Evaluation of Responsiveness to Reduced-Dose Rituximab in Corticotropin/Intravenous Immunoglobulin/Rituximab Combination Immunotherapy for Opsoclonus-Myoclonus Syndrome

BackgroundRituximab (anti-CD20) has been used as B-cell-targeted intervention to treat opsoclonus-myoclonus syndrome. Due to isolated reports of chronic hypogammaglobulinemia and B lymphopenia following rituximab in several disorders, and rapid B-cell depletion after a few doses, we reduced the dosage 20% in our clinical practice. MethodsIn this Institutional Review Board-approved retrospective study, 32 children with opsoclonus-myoclonus syndrome and cerebrospinal fluid B-cell expansion had received front-loaded adrenocorticotropic hormone, intravenous immunoglobulin, and rituximab combination immunotherapy for de novo opsoclonus-myoclonus syndrome. Parametric statistical analysis compared 10 children receiving 1200 mg/m2 of rituximab (300 mg/m2 × 4) and 22 receiving 1500 mg/m2 (375 mg/m2 × 4). Clinical response had been video documented and scored by a blinded observer. ResultsIn both groups, motor severity (total score) lessened by ≥76% and cerebrospinal fluid B cells were similarly depleted (≥95%) six months after treatment. None of the treated patients remained unable to walk independently. Serum IgM depletion was analogous in the 1200 mg/m2 (−73%) and 1500 mg/m2 group (−64%). The relapse frequency was similar in both groups. Side effects were principally steroidal, tolerable, and transient. Circulating B-cell repopulation was comparable. ConclusionsThe reduced-dose of rituximab in rituximab combination immunotherapy was as effective and well tolerated as the standard dose, and provided rapid, early therapeutic intervention in opsoclonus-myoclonus syndrome. Pending a long-term prospective study, these are proof-of-concept data in support of challenging the dose of rituximab in various disorders, which may have different dose requirements.

Monitoring B-cell repopulation after depletion therapy in neurologic patients

ObjectiveTo determine the factors that influence B-cell repopulation after B-cell depletion therapy in neurologic patients and derive recommendations for monitoring and dosing of patients.MethodsIn this study, we determined the association of body surface area (BSA; calculated by body weight and height with the Dubois formula), sex, pretreatment therapy, age, CSF data, and white blood cell counts with the risk and timing of B-cell repopulation, defined as 1% CD19+ cells (of total lymphocytes), following 87 B cell–depleting anti-CD20 treatment cycles of 45 neurologic patients (28 women; mean age ± SD, 44.5 ± 15.0 years).ResultsPatients with a larger BSA had a higher probability to reach 1% CD19+ cells than those with a smaller BSA (p < 0.05) following B-cell depletion therapy, although those patients had received BSA-adapted doses of rituximab (375 mg/m2). Sex, pretreatment, age, CSF data, or absolute lymphocyte and leukocyte counts during treatment did not significantly influence CD19+ B-cell recovery in the fully adjusted models. Intraindividual B-cell recovery in patients with several treatment cycles did not consistently change over time.ConclusionsB-cell repopulation after depletion therapy displays both high inter- and intra-individual variance. Our data indicate that a larger BSA is associated with faster repopulation of B cells, even when treatment is adapted to the BSA. A reason is the routinely used Dubois formula, underestimating a large BSA. In these patients, there is a need for a higher therapy dose. Because B-cell count–dependent therapy regimes are considered to reduce adverse events, B-cell monitoring will stay highly relevant. Patients' BSA should thus be determined using the Mosteller formula, and close monitoring should be done to avoid resurgent B cells and disease activity.

Developing biomarkers for predicting clinical relapse in pemphigus patients treated with rituximab

Rituximab is an effective therapy for pemphigus, although relapses are common. To identify biomarkers to predict relapse of pemphigus following rituximab treatment. In this retrospective cohort study, 62 patients with pemphigus treated with 99 rituximab cycles provided longitudinal clinical scoring and biomarker data, including levels of CD19+ B cells, CD4+ T cells, and desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) autoantibodies. An extended time-variant Kaplan-Meier estimator and extended Cox model were applied. Relapse was rare before B-cell repopulation. Univariate analysis revealed low CD4 count (<400cells/μL) to predict relapse (P<.001). A positive result of testing for Dsg1 (>20 IU) was predictive of relapse among patients with mucocutaneous disease (hazard ratio, 6.40; P=.019); a positive result of testing for Dsg3 (>20 IU) was predictive in patients with mucocutaneous and mucosal disease (hazard ratio, 32.92; P<.001). Multivariable analysis revealed that every CD4 value increase of 200 decreases the hazard ratio for relapse by 35% (P=.029). A positive result of testing for Dsg1 increases the risk for relapse by a factor of 12.32 in patients with mucocutaneous disease (P=.001); positive result of testing for Dsg3 increases risk for relapse by 28.38 in patients with mucosal and mucocutaneous disease (P=.006). Limitations include the retrospective design and inconsistent follow-up. Relapse is associated with B-cell repopulation, low CD4+ T -cell count, and positive result of testing for Dsg1 and Dsg3.

Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review.

BackgroundThe clinical outcomes following rituximab (RTX) treatment in patients with systemic lupus erythematosus (SLE) is highly variable. We aimed to identify predictive and prognostic factors associated with RTX therapy outcomes in patients with SLE.MethodsStudies in adults and paediatric patients with SLE were included. We included randomized clinical trials (RCTs) for predictors of differential treatment effect and cohort studies for potential prognostic factors in patients treated with RTX (global clinical, cutaneous and renal either response or relapse, and side effects). Methodological quality was assessed using Cochrane Collaboration Risk of Bias tool and the Quality In Prognosis Studies Tool (QUIPS) for RCTs and cohort studies, respectively. The quality of subgroup analyses testing predictors of differential treatment response was also evaluated. A best evidence synthesis was performed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework.ResultsSixteen articles were included (3 from 2 RCTs and 13 from 6 cohort studies). The overall quality of evidence (QoE) was low to very low (GRADE framework). QoE for predictive factors based on RCTs analysing sociodemographic variables, was rated very low due to the lack of interaction tests, limited power of subgroup analyses, study limitations, and imprecisions. Disease-related factors including clinical phenotype and severity, baseline anti-ENA antibodies and anti-Ro antibodies, interleukin (IL) 2/21 single nucleotide polymorphism (SNP), as well as post-RTX complete B-cell depletion and earlier B-cell repopulation showed some evidence for prognostic value, but were rated low to very low QoE because of early phase of investigation (exploratory analysis), insufficient adjustment for confounding in most studies, high risk of bias, inconsistency, and imprecisions.ConclusionsTo date, studies addressing prognostic factors are hypothesis generating and cannot be used to make any specific recommendations for routine clinical practice. A number of potential predictors/prognostic factors were identified, which require to be validated as being specific for response to RTX therapy and to enable more personalised use of this agent.

Relapse of lupus after B cell depletion therapy is associated with loss of apoptotic debris clearing marginal zone macrophages in BXD2 mice (THER5P.911)

Abstract B-cell depletion therapy (BCDT) is used to treat autoimmune diseases but development of autoreactive B cells can occur during repopulation. Marginal zone macrophages (MZMs) are essential for tolerogenic clearance of apoptotic debris. Maintenance of MZMs requires MZ B cells. To determine if BCDT using anti-CD20 depletes MZ B cells and promote the loss of MZMs, lupus prone BXD2 mice were administered α-CD20 or isotype control (250 µg/single dose i.v.). This resulted in depletion of &amp;gt;80% B cells in the spleen at week 2 in BCDT group. This was associated with increased uncleared apoptotic debris in the spleen MZ and a dramatic decline in MZMs. By 5 weeks of BCDT, the B-cell repopulation rate was &amp;gt;50%. However, there was a significantly elevated expression of type I IFN signature genes Usp18 and Oasl in repopulated MZ precursor B cells in anti-CD20 group. There was a 2.8-fold increase in PNA+Fas+ CD19+ germinal center B cells in the spleens of anti-CD20-treated BXD2 mice, compared to isotype-treated mice. At week 9, the serum titers of IgG autoantibodies against DNA, histone, and malondialdehyde, a lipid peroxidation product associated with apoptotic blebs, were markedly increased in the α-CD20-treated BXD2 mice than control group. These results indicate that BCDT in BXD2 mice promotes an environment with excessive uncleared apoptotic debris which enhanced the effects of type I IFNs on repopulating B cells, leading to the return of autoreactive B cells.

Lymphocyte subset dynamics following alemtuzumab treatment in patients who relapsed on a prior therapy

Background: Alemtuzumab, a humanized monoclonal antibody, is approved in over 30 countries for active relapsing–remitting multiple sclerosis (RRMS). Alemtuzumab selectively targets CD52 to deplete circulating T and B lymphocytes, followed by a distinctive pattern of T- and B-cell repopulation. In the phase 3 CARE-MS II study, alemtuzumab had significant positive treatment effects on clinical efficacy in RRMS patients with disease activity despite prior disease-modifying therapy.

Reconstitution of the peripheral B lymphocyte compartment in patients with ANCA-associated vasculitides treated with rituximab for relapsing or refractory disease

While in patients with rheumatoid arthritis B-cell repopulation starts within 9 months after rituximab (RTX) therapy, a delayed B-cell repopulation was reported in some RTX-treated patients with ANCA-associated vasculitides (AAV). To date, the frequency of AAV patients with impaired peripheral B-cell regeneration and the mechanisms leading to the constricted regenerative capacity are unknown. We analyzed the B-cell repopulation kinetic in 37 AAV patients treated with RTX followed by maintenance immunosuppressants. We report on serum concentrations of the B-cell-activating factor BAFF, immunoglobulins and B-cell subpopulations in patients that relapsed after RTX. B-cells were re-detectable in only one patient within 9 months after RTX. In 14 patients (41%), B-cell repopulation started later, after a mean observation time of 21 months. Only seven of these patients had detectable B-cells within the first year after RTX. Twenty patients (59%) had no B-cell reconstitution within the observation period. BAFF was increased in RTX-treated AAV patients compared to healthy controls and correlated inversely with peripheral B-cell numbers, IgG- and IgA concentrations. Immunoglobulin concentrations declined significantly after RTX and the IgG concentration correlated with B-cell numbers. Thirteen patients relapsed after RTX. Relapses occurred exclusively either after B-cell reconstitution had started or were accompanied by rising ANCA titres. In relapsed patients, the B-lymphocyte compartment consisted mainly of switched memory B-cells. Our data indicate that RTX treatment can induce secondary immunodeficiency in AAV, with hypogammaglobulinemia and long-lasting B-lymphopenia. Further studies are needed to define the pathophysiology of the impaired B-cell development in RTX-treated AAV patients.

Responsiveness to reduced dosage of rituximab in Chinese patients with neuromyelitis optica

To determine the effect of a lower dose of rituximab in depleting B lymphocytes, maintaining low B-cell counts, and relapse in patients with neuromyelitis optica (NMO) and NMO spectrum disorders. We treated 5 Chinese patients with deteriorating NMO and NMO spectrum disorders with a 100-mg IV infusion of rituximab once a week for 3 consecutive weeks, followed by additional infusion of the same dosage depending on circulating B-cell repopulation. This reduced dosage of rituximab was sufficient to deplete B cells and maintain low B-cell counts. None of the treated patients experienced relapse, and all patients exhibited stabilized or improved neurologic function during the 1-year follow-up period. MRI revealed the absence of new lesions, no enhancement in spinal cord and brain, a significant shrinkage of spinal cord segments, and a reduction/disappearance of previous brain lesions. A lower dosage of rituximab may be sufficient in depleting B cells, maintaining low B-cell counts, and preventing disease progression in Chinese patients with NMO.

SAT0163 B-Cell Homeostasis is Disturbed by Immunosuppressive Therapies and After Treatment with Rituximab in Patients with Anca-Associated Vasculitides

BackgroundB-lymphocytes are involved in the pathogenesis of ANCA-associated vasculitides (AAVs), but the knowledge about alterations in peripheral blood B-lymphocytes of AAV patients and the changes in B-lymphocyte subsets after immunosuppressive...

B-cell numbers and phenotype at clinical relapse following rituximab therapy differ in SLE patients according to anti-dsDNA antibody levels

Objectives. To correlate the kinetics of B-cell repopulation with relapse after B-cell depletion therapy in SLE patients and address whether variation in relapse rate, B-cell numbers and phenotype are related to anti-dsDNA antibody levels.Methods. Sixty-one patients with refractory SLE were treated with a standard rituximab regimen. Clinical and serological measures of disease activity and B-cell numbers were assessed. B-cell phenotype was examined in a subgroup of patients by flow cytometry.Results. Disease relapse was substantially delayed beyond B-cell repopulation, and early relapse was associated with a faster rate of repopulation. At relapse, B-cell numbers were significantly lower than at baseline in patients with high anti-dsDNA antibody levels (>100 IU/ml) but not in patients with low anti-dsDNA antibody levels. Of the patients with high anti-dsDNA antibodies at baseline, levels fell significantly only in those patients who remained in remission after repopulation. Relapse with high anti-dsDNA antibody levels was associated with an increased percentage of IgD−CD27hi plasmablasts, whereas relapse with low anti-dsDNA antibody levels was accompanied by an increased percentage of IgD−CD27− B cells.Conclusion. Anti-dsDNA antibody levels distinguished two patient groups, which differ in their B-cell number and phenotype at relapse following rituximab, and suggest that different B-cell pathologies exist in SLE. The data imply that B-cell numbers should be kept very low for a sustained period in patients with high dsDNA binding, therefore justifying a more aggressive regimen.

Comparison of immunological parameters in patients with pemphigus vulgaris following rituximab and IVIG therapy

Information on certain immunological parameters in patients with pemphigus vulgaris (PV) treated with rituximab (RTX) and intravenous immunoglobulin (IVIG) therapy is limited. Comparing immunological parameters in patients who achieved long-term clinical remission (LTR) with those who relapsed. Retrospective analysis of 19 patients treated at a single centre using the same protocol. Comparisons were made between patients who went into LTR and those who relapsed following completion of the protocol. Treatments prior to IVIG and RTX included prednisone with or without an immunosuppressive agent. The immunological parameters measured included peripheral blood B cells (CD19+), serum quantitative immunoglobulin levels, and levels of antibodies to desmogleins (Dsg) 1 and 3. Eleven patients achieved LTR. Eight patients developed 15 relapses. The mean follow-up time for the LTR group was 29·6±11·2months, and for the relapse group, 40·0±7·0 months. There were no significant differences in times to B-cell depletion, repopulation, or recovery to pretreatment levels between the patients who achieved LTR and those who relapsed. Recurrences usually occurred after B-cell repopulation. Repeated treatments did not influence the time to B-cell repopulation. IgM levels were decreased after therapy and remained decreased. A consistent increase in anti-Dsg1 antibody levels occurred at the time of relapse in patients with mucocutaneous disease. The majority of patients treated with rituximab and IVIG therapy achieved LTR. Retreatment of relapses can induce LTR. Decreased serum IgM levels persisted following treatment. Increases in anti-Dsg1 antibodies during therapy in patients with mucocutaneous disease suggests a close follow-up for a potential relapse is required.

Rituximab dosing and monitoring strategies in neuromyelitis optica patients: creating strategies for therapeutic success

Background: Neuromyelitis optica (NMO) is an autoimmune condition that predominantly causes severe optic neuritis and transverse myelitis. Rituximab therapy has dramatically improved patient care, but standardized dosing regimens and guidelines are lacking. Objectives: The objective of this study was to define a rituximab dosing strategy for NMO patients that achieves the lowest rate of relapses. Methods: This was a retrospective chart review of patients treated with various doses of rituximab. Results: Combining data from the NMO and multiple sclerosis (MS) patients, identified that the mean number of days after a 100 mg dose of rituximab until the CD19 population was greater than 2% was 99 days (standard deviation 36, range 43–172). When allowed to rise, the mean number of days after a 1000 mg dose of rituximab until the CD19 population was greater than 2% was 184 (standard deviation 72, range 52–288). The median number of days until a CD19 percentage of 2% was achieved was 133 days in the 100 mg dosing arm and 259 days in the 1000 mg dosing arm. Analysis of the survival curves via both the Mantel–Cox log-rank test and the Wilcoxon test determined that the difference between medial survival for 100 and 1000 mg doses was statistically significant with p-values <0.0001. Conclusions: Low doses of rituximab have a high rate of early B-cell repopulation. Any NMO patient treated with rituximab should be followed with monthly CD19 counts in order to identify the rare, but clinically significant, early repopulators.

Chemokine/cytokine profiling after rituximab: Reciprocal expression of BCA-1/CXCL13 and BAFF in childhood OMS

The aim of the study was to test the hypothesis that B-cell repopulation following rituximab (anti-CD20) therapy is orchestrated by chemokines and non-chemokine cytokines. Twenty-five children with opsoclonus–myoclonus syndrome (OMS) received rituximab with or without conventional agents. A comprehensive panel of 40 chemokines and other cytokines were measured in serum by ELISA and multiplexed fluorescent bead-based immunoassay. Serum BAFF concentration changed dramatically (even after first infusion) and inversely with B-cell depletion/repopulation and CXCL13 concentration at 1, 3, and 6 months. Negative correlations were found for BAFF concentration vs blood B cell percentage and serum CXCL13 concentration; positive correlations with serum rituximab concentrations. Six months after initiation of therapy, no significant difference in the levels of APRIL, CXCL10, IL-6, or 17 other cytokines/chemokines were detected. These data reveal a major role for BAFF in peripheral B cell repopulation following rituximab-induced B-cell depletion, and novel changes in CXCL13. ClinicalTrials.gov NCT0024436.

CXCL13: a novel biomarker of B-cell return following rituximab treatment and synovitis in patients with rheumatoid arthritis

The B-cell chemokine, CXCL13, is a proposed serum biomarker of synovitis in RA. Its behaviour in the context of B-cell depletion therapy and reconstitution was studied during treatment of RA with rituximab. Serum samples from 20 RA patients were analysed for CXCL13, RF-IgM and anti-CCP by ELISA before and 2 and 6 months following rituximab treatment. B cells were monitored by flow cytometry. Gene expression in blood and synovial biopsies was determined by qPCR. Patients with detectable B cells at 6 months had significantly higher levels of CXCL13 and RF-IgM and slightly higher levels of anti-CCP throughout the study, including at baseline, compared with patients with undetectable B cells at 6 months. Conversely, 10 of 12 patients with high baseline CXCL13 had detectable circulating B cells at 6 months, whereas no B cells could be detected at 6 months in patients with low baseline CXCL13. Synovial CXCL13 expression at baseline correlated significantly with serum CXCL13 levels, and the synovium of patients with high serum CXCL13 expressed elevated levels of IL-1β, IL-8, MMP1 and MMP3. In addition, synovial CXCL13 expression correlated significantly with several synovial inflammatory markers. Serum CXCL13 is predictive of the rate of B-cell repopulation following a course of rituximab in RA. Serum CXCL13 correlates with synovial CXCL13 measured at a single joint, suggesting synovitis as an important source of circulating CXCL13. Within the synovium, CXCL13 expression is highly correlated with markers of synovitis. ClinicalTrials.gov, http://clinicaltrials.gov/, NCT00147966.

B-cell-activating factor receptor expression on naive and memory B cells: relationship with relapse in patients with rheumatoid arthritis following B-cell depletion therapy

ObjectivesTo examine the expression of B-cell-activating factor receptor (BAFF-R) on naive CD27− and memory CD27+ B cells in normal individuals and patients with rheumatoid arthritis (RA) undergoing B-cell depletion therapy...

Clinical improvements in proliferative vs membranous lupus nephritis following B-cell depletion: pooled data from two cohorts

To compare the clinical results after treatment with B-cell depleting therapy in patients with membranous (WHO Class V) vs proliferative (WHO Class III or IV) lupus nephritis (LN). Data were compiled from two European centres on all patients with LN who were treated with i.v. rituximab (RTX) in a combination protocol with i.v. cyclophosphamide and steroids. Laboratory and serological evaluations were performed at 3, 6 and 12 months of follow-up. No immunosuppressive drugs were given before B-cell repopulation. Forty-three patients, 28 with proliferate and 15 with membranous LN by renal biopsy, were evaluated. Six months after treatment with RTX, both the membranous and the proliferative LN patients had a significant reduction in proteinuria and an increase in serum albumin. The main improvements were observed during the first 6 months and only minor non-significant changes in albumin and proteinuria were observed thereafter. As expected, the patients with membranous nephritis had lower anti-dsDNA titres and higher complement C3 levels at baseline, but in both groups a significant reduction in anti-dsDNA titre and improvements in complement C3 levels were seen during the first 6 months after treatment; the kinetics of improvement were similar in both groups. The clinical course following B-cell depleting therapy is strikingly similar between patients with membranous and those with proliferative LN. These observational data suggest that, if controlled studies confirm the efficacy of B-cell depleting therapy in proliferative nephritis, clinicians may reasonably consider such therapy in membranous LN.

BAFF May Modulate the Rate of B-Cell Repopulation After Rituximab Therapy for Acute Renal Transplant Rejection

BAFF May Modulate the Rate of B-Cell Repopulation After Rituximab Therapy for Acute Renal Transplant Rejection

Class-switched B cells display response to therapeutic B-cell depletion in rheumatoid arthritis

IntroductionReconstitution of peripheral blood (PB) B cells after therapeutic depletion with the chimeric anti-CD20 antibody rituximab (RTX) mimics lymphatic ontogeny. In this situation, the repletion kinetics and migratory properties of distinct developmental B-cell stages and their correlation to disease activity might facilitate our understanding of innate and adaptive B-cell functions in rheumatoid arthritis (RA).MethodsThirty-five 'RTX-naïve' RA patients with active arthritis were treated after failure of tumour necrosis factor blockade in an open-label study with two infusions of 1,000 mg RTX. Prednisone dose was tapered according to clinical improvement from a median of 10 mg at baseline to 5 mg at 9 and 12 months. Conventional disease-modifying antirheumatic drugs were kept stable. Subsets of CD19+ B cells were assessed by flow cytometry according to their IgD and CD27 surface expression. Their absolute number and relative frequency in PB were followed every 3 months and were determined in parallel in synovial tissue (n = 3) or synovial fluid (n = 3) in the case of florid arthritis.ResultsSix of 35 patients fulfilled the European League Against Rheumatism criteria for moderate clinical response, and 19 others for good clinical response. All PB B-cell fractions decreased significantly in number (P < 0.001) after the first infusion. Disease activity developed independently of the total B-cell number. B-cell repopulation was dominated in quantity by CD27-IgD+ 'naïve' B cells. The low number of CD27+IgD- class-switched memory B cells (MemB) in the blood, together with sustained reduction of rheumatoid factor serum concentrations, correlated with good clinical response. Class-switched MemB were found accumulated in flaring joints.ConclusionsThe present data support the hypothesis that control of adaptive immune processes involving germinal centre-derived, antigen, and T-cell-dependently matured B cells is essential for successful RTX treatment.

The effects of B‐cell depletion therapies on humoral immune responses in normal mice

Anti‐CD20 mediated B cell depletion is a therapy for treating rheumatoid arthritis and B‐cell malignancies. To examine how B cell depletion affects an individual's capacity to generate antibody responses we assessed in a mouse model primary and secondary antibody responses after treatment with anti‐mouse CD20 and/or BAFFR‐Ig. BALB/c mice dosed with anti‐CD20 one week prior to primary TNP‐KLH immunization had a 93% decrease in anti‐TNP IgG titers at day 10 compared to controls. Mice treated with anti‐CD20 one week prior to immunization with TNP‐Ficoll had a ~50% increase in TNP‐specific IgG and IgM titers. The secondary antibody response to TNP‐KLH was not significantly affected by anti‐CD20 treatment one week prior to immunization. BAFFR‐Ig treatment reduced the secondary response to TNP‐KLH by 57%. Treatment of mice with the combination of anti‐CD20 and BAFFR‐Ig dramatically reduced secondary antibody responses to either antigen. After B‐cell repopulation all treatment groups mounted a strong response to a tertiary challenge. Therefore, B cell depletion with anti‐CD20 results in a strong reduction in the primary antibody response to a neoantigen, however memory B cells appear resistant to anti‐CD20 treatment. Simultaneous anti‐CD20 and BAFFR‐Ig treatment results in elimination of the secondary response by blocking memory B cell activation but does not deplete memory B cells.

Rituximab therapy for juvenile-onset systemic lupus erythematosus

Rituximab (RTX), an anti-CD20 monoclonal antibody, has been proposed for use in the therapy of systemic lupus erythematosus (SLE). We present the initial long-term experience of the safety and efficacy of rituximab for treatment of SLE in children. Eighteen patients (mean age 14 ± 3 years) with severe SLE were treated with rituximab after demonstrating resistance or toxicity to conventional regimens. There was a predominance of female (16/18) and ethnic African (13/18) patients. All had lupus nephritis [World Health Organization (WHO) classes 3–5] and systemic manifestations of vasculitis. Clinical disease activity of the SLE was scored with the SLE-disease activity index 2K (SLEDAI-2K). Patients were followed-up for an average of 3.0 ± 1.3 years (range 0.5 to 4.8 years). B-cell depletion occurred within 2 weeks in all patients and persisted for up to 1 year in some. Clinical activity scores, double-stranded DNA (dsDNA) antibodies, renal function and proteinuria [urine protein to creatinine ratio (Upr/cr)] improved in 93% of the patients. Five patients required multiple courses of RTX for relapse, with B-cell repopulation. One died of infectious endocarditis related to severe immunosuppression. In conclusion, our data support the efficacy of rituximab as adjunctive treatment for SLE in children. Although rituximab was well tolerated by the majority of patients, randomized controlled trials are required to establish its long-term safety and efficacy.