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Rituximab (RTX) has been used to treat B cell lineage lymphoma/leukemia or autoimmune or autoinflammatory disorders. RTX therapy has been extensively applied to cases of frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome. Rituximab-induced serum sickness (RISS) has been recognized as a rare severe type-3 hypersensitivity reaction in patients treated with RTX. We herein report a 10-year-old girl with RISS in FRNS. She was diagnosed with RISS based on characteristic symptoms, such as a fever, rash, arthritis, or proteinuria, during RTX therapy associated with a high level of human anti-chimeric antibody. Even after recovering from acute symptoms by RISS, she suffered from worsening relapses of nephrotic syndrome. The symptoms of RISS are non-specific, resembling viral infections, autoinflammatory diseases and Kawasaki disease, especially in children. While RISS is a rare complication among patients with nephrotic syndrome, it should be carefully considered as a severe complication in patients being treated with RTX.

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Rituximab (RTX) is a murine-human chimeric monoclonal antibody against CD20 that has been proven effective for preventing relapse in frequently-relapsing or steroid-dependent nephrotic syndrome (NS). Serum sickness, a type-3 hypersensitivity reaction resulting from injection of foreign proteins, has been reported in patients treated with RTX. Herein, we describe a case of RTX-induced serum sickness (RISS) in a 6-year-old boy with steroid-dependent NS. He presented to the hospital with fever and polyarthralgia at 10 days after his fourth dose of RTX. Although he was started on empiric intravenous antibiotics, there was no evidence of septic arthritis and his symptoms resolved over the course of 4 days. He was diagnosed with RISS based on the chronology of RTX administration and the acute-onset self-limiting course of the polyarthritis. His serum human anti-chimeric antibody (HACA) level on day 53 exceeded the limit of quantification (5000 ng/mL). The pathogenesis of RISS and the role of HACAs remain unclear. It is important for clinicians to recognize RISS, because further infusions of RTX may cause more severe reactions in patients with a history of RISS.

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BACKGROUND: Rituximab is a mouse-human chimeric anti-CD20 monoclonal antibody and has been increasingly used for preventing relapses in NMOSDs. The clinical relevance of Anti-Rituximab antibodies (ARA) against Rituximab in NMOSDs is unknown. METHODS: Nineteen NMOSDs patients receiving repeated 100mg Rituximab treatment were recruited. The ARA was quantitatively analyzed by enzyme linked immunoassay. Annualized relapse rate (ARR) and Expanded Disability Status Scale (EDSS) were analyzed concurrently. RESULTS: ARR was reduced markedly since starting Rituximab therapy in the majority (78.9%) of NMOSDs patients. 36.9% (7/19) patients were ARA positive. There was no significant difference in the improvement of ARR and EDSS after treatment with Rituximab in either ARA positive or negative groups. The frequency of Rituximab reinfusion was higher in patients with ARA, suggesting that the presence of ARA led to an increased frequency of Rituximab reinfusion to maintain B cell depletion. CONCLUSION: The majority of (78.9%) patients with NMOSDs were responsive to low dose Rituximab. The presence of ARA is associated with the requirement for increased frequency of Rituximab reinfusion to maintain treatment response in NMOSDs. In patients with ARA it might be necessary to detect ARA levels and monitor B cell depletion closely, or even attempt other treatments.

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SM03, a chimeric antibody that targets the B-cell restricted antigen CD22, is currently being clinically evaluated for the treatment of lymphomas and other autoimmune diseases in China. SM03 binding to surface CD22 leads to rapid internalization, making the development of an appropriate cell-based bioassay for monitoring changes in SM03 bioactivities during production, purification, storage, and clinical trials difficult. We report herein the development of an anti-idiotype antibody against SM03. Apart from its being used as a surrogate antigen for monitoring SM03 binding affinities, the anti-idiotype antibody was engineered to express as fusion proteins on cell surfaces in a non-internalizing manner, and the engineered cells were used as novel "surrogate target cells" for SM03. SM03-induced complement-mediated cytotoxicity (CMC) against these "surrogate target cells" proved to be an effective bioassay for monitoring changes in Fc functions, including those resulting from minor structural modifications borne within the Fc-appended carbohydrates. The approach can be generally applied for antibodies that target rapidly internalizing or non-surface bound antigens. The combined use of the anti-idiotype antibody and the surrogate target cells could help evaluate clinical parameters associated with safety and efficacies, and possibly the mechanisms of action of SM03.

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