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The bm12 Inducible Model of Systemic Lupus Erythematosus (SLE) in C57BL/6 Mice
Published on: November 1, 2015
B cell depletion therapy for 19 patients with refractory systemic lupus erythematosus
A Podolskaya1, M Stadermann, C Pilkington
1Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Trust, London, WC1N 3JH, UK.
Insights
Rituximab therapy effectively reduced disease activity in children with childhood-onset systemic lupus erythematosus (SLE), showing significant improvements in key health markers with minimal serious side effects.
Area of Science:
- Pediatric Rheumatology
- Immunology
- Pharmacology
Background:
- B cell dysregulation is a key factor in childhood-onset systemic lupus erythematosus (SLE).
- B cell depletion therapy offers a potential treatment avenue for pediatric SLE.
- Evaluating rituximab's safety and efficacy in children is crucial due to limited data.
Purpose of the Study:
- To assess the safety and efficacy of rituximab in treating pediatric SLE.
- To evaluate rituximab's impact on disease activity and immunological parameters in children with SLE.
- To present the largest pediatric cohort treated with rituximab for SLE.
Main Methods:
- Retrospective review of 19 children (median age 14) with SLE treated with rituximab.
- Assessment of British Isles Lupus Assessment Group (BILAG) scores and biochemical, hematological, and immunological parameters pre- and post-treatment.
- Rituximab (750 mg/m(2) IV twice) administered for acute, life- or organ-threatening, or refractory SLE symptoms.
Main Results:
- Significant reduction in SLE disease activity (BILAG scores decreased from 14 to 6, p<0.005).
- Improvements observed in renal function (eGFR 54 to 68 ml/min/1.73 m(2), p=0.07), immunological markers (C3: 0.46 to 0.83 g/l, p=0.02), and hematological parameters (hemoglobin 9.7 to 10.3 g/dl, p=0.04).
- No serious adverse events reported, with five cases of herpes zoster.
Conclusions:
- Rituximab, combined with standard immunosuppressants, demonstrated safety and efficacy in this pediatric SLE cohort.
- Further randomized controlled trials are warranted to confirm rituximab's therapeutic role in pediatric SLE.
- Rituximab represents a promising option for managing severe childhood-onset SLE.
Objective:
B cell dysregulation is involved in the development of childhood-onset systemic lupus erythematosus (SLE). The safety and efficacy of B cell depletion therapy is evaluated in the the largest series of children to be presented in the literature.
Methods:
19 children (89% female) with SLE, aged 6-16 (median 14) years, treated with rituximab in a single centre were retrospectively reviewed. The British Isles Lupus Assessment Group (BILAG) index and biochemical, haematological and immunological parameters were evaluated before and after treatment, with the primary outcome assessed as normal results. Rituximab therapy was used for acute life- or organ-threatening symptoms or symptoms that had not responded to standard treatment. The range of symptoms included lupus nephritis, cerebral lupus and severe general symptoms. Rituximab 750 mg/m(2) was given intravenously twice, usually within a 2-week period. Patients were followed up for 6-38 (median 20) months.
Results:
Rapid reduction of SLE disease activity was observed within the first month, represented by a reduction of BILAG scores (14 to 6, p<0.005) and an improvement in renal function (estimated glomerular filtration rate of 54 to 68 ml/min/1.73 m(2), p = 0.07), immunological (complement C3: 0.46 to 0.83 g/l, p = 0.02) and haematological (haemoglobin: 9.7 to 10.3 g/dl, p = 0.04) parameters. No serious side effects were observed, except for herpes zoster in five cases.
Conclusion:
In our cohort of children, rituximab was safe and effective when used in combination with standard immunosuppressive agents. Randomised controlled studies are needed to further evaluate the safety and efficacy of rituximab therapy.