High-Dose IV Administration of Rasburicase Suppresses Anti-rasburicase Antibodies, Depletes Rasburicase-Specific Lymphocytes, and Upregulates Treg Cells

Xu, Hui; Max, Edward E.

doi:10.1208/s12248-020-00461-0

Cited by 7 publications

(2 citation statements)

References 70 publications

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“…Of note, the optimal dosage of IRBP 1-20 is central to the induction rate. Too high a dosage may cause T cell apoptosis or may induce T regulatory cells instead and, hence, suppress the immune response (32,33). Our data suggested that only the appropriate peptide dose was useful for enhancing induction efficacy and inflammation severity, and 500 μg IRBP 1-20 might be the optimal dosage for EAU induction in C57BL/6 mice (Figure 2).…”

Section: Discussionmentioning

confidence: 82%

Optimization of determinant factors associated with the efficiency of experimental autoimmune uveitis induction in C57BL/6 mice

Yang¹,

Yang²,

Huang³

et al. 2022

Ann Transl Med

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Background: Experimental autoimmune uveitis (EAU) is a widely used animal model for uveitis research.The C57BL/6 mouse strain is the most commonly used mouse strain in the research of genetic modification, but C57BL/6 mice are not sufficiently susceptible to EAU induction, partly due to experimental factors. This work aims to optimize relevant factors to improve the efficiency of EAU induction in C57BL/6 mice.Methods: To induce EAU, mice were immunized via intraperitoneal injection with pertussis (PTX) and subcutaneous injection with interphotoreceptor retinoid-binding protein peptide 1-20 (IRBP 1-20 ) emulsified with complete Freund's adjuvant (CFA). The severity of inflammation was assessed using several approaches.The relevant experimental factors were evaluated, including methods of emulsification and doses of peptide and PTX.Results: Uveitis occurred at 8-12 days after immunization and reached its peak at 18-20 days, while T helper type 17 (Th17) cells peaked earlier at 14-18 days after immunization. Based on clinical and histological scores, 500 μg of IRBP peptide was the optimal dose required to induce EAU. The PTX dose demonstrated no influence on EAU incidence, but potentially affected the severity of uveitis. A single injection of 1,000 ng of PTX induced the most severe EAU and the highest proportion of Th17 cells.Compared to extruded emulsion, sonicated emulsion produced a higher incidence, higher histological score, and a 2-day-earlier onset of EAU. Electron microscopy showed a significantly different microstructure between the 2 emulsions.Conclusions: This work optimized the protocols of EAU induction and obtained a high and stable induction rate with severe inflammation in the C57BL/6 mouse strain. Our results facilitate future experimental research involving uveitis.

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Section: Discussionmentioning

confidence: 82%

Optimization of determinant factors associated with the efficiency of experimental autoimmune uveitis induction in C57BL/6 mice

Yang¹,

Yang²,

Huang³

et al. 2022

Ann Transl Med

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“…Encouraging Treg differentiation presents a novel method for addressing HUA and its subsequent complications. The incidence of apoptosis, along with the depletion of circulating B-lymphocytes and the upregulation of Treg cells post-labrylase administration, proposes that this recombinant uricase treatment for HUA might influence outcomes by inhibiting B-cells to bolster Treg ( 102 ). These findings highlight the significance of manipulating the Th17/Treg balance as a treatment strategy for HUA.…”

Section: Treg Cellsmentioning

confidence: 99%

The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications

Li,

Yuan,

Deng

et al. 2023

Front. Immunol.

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Changes in lifestyle induce an increase in patients with hyperuricemia (HUA), leading to gout, gouty arthritis, renal damage, and cardiovascular injury. There is a strong inflammatory response in the process of HUA, while dysregulation of immune cells, including monocytes, macrophages, and T cells, plays a crucial role in the inflammatory response. Recent studies have indicated that urate has a direct impact on immune cell populations, changes in cytokine expression, modifications in chemotaxis and differentiation, and the provocation of immune cells by intrinsic cells to cause the aforementioned conditions. Here we conducted a detailed review of the relationship among uric acid, immune response, and inflammatory status in hyperuricemia and its complications, providing new therapeutic targets and strategies.

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Use of rasburicase to improve kidney function in children with hyperuricemia and acute kidney injury

Herrero-Goñi,

Zugazabeitia Irazábal,

Madariaga

et al. 2023

Clin Exp Nephrol

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Background Hyperuricemia contributes to decrease in kidney function and induces additional renal damage in children with acute kidney injury (AKI). Rasburicase oxidizes uric acid (UA), decreasing its serum quantities in less than 24 h. Methods This is a retrospective study involving hospitalized patients under 18 years of age with underlying pathology diagnosed with AKI and severe hyperuricemia treated with rasburicase over a 4-year period. Results We describe 15 patients from 4 days of life to 18 years (median: 4.4 years). Seventy-three percent had known underlying pathologies. All presented worsening of basal renal function or AKI data. All received the usual medical treatment for AKI without response. Twenty percent received an extrarenal depuration technique. All had hyperuricemia with a mean (± SD) of 13.1 (± 2.19) mg/dl. After rasburicase administration UA levels fell to a mean (± SD) of 0.76 (± 0.62) mg/dl (p < 0.001) in less than 24 h. In parallel, a decrease in the mean plasma creatinine was observed (2.92 mg/dl to 1.93 mg/dl (p = 0.057)) together with a significant improvement of the mean glomerular filtration rate (16.3 ml/min/1.73 m2 to 78.6 ml/min/1.73 m2) (p = 0.001)). No side effects were recorded. Kidney function normalized in all cases or returned to baseline levels. Conclusions Although the use of rasburicase is not routinely approved in pediatric patients with severe hyperuricemia and AKI, it has been used successfully without complications, and helped prevent progressive kidney damage. This study could serve as a basis for suggesting the off-label use of rasburicase for the management of complex pediatric patients in whom UA plays an important role in the development of AKI.

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High-Dose IV Administration of Rasburicase Suppresses Anti-rasburicase Antibodies, Depletes Rasburicase-Specific Lymphocytes, and Upregulates Treg Cells

Cited by 7 publications

References 70 publications

Optimization of determinant factors associated with the efficiency of experimental autoimmune uveitis induction in C57BL/6 mice

Optimization of determinant factors associated with the efficiency of experimental autoimmune uveitis induction in C57BL/6 mice

The dysregulation of immune cells induced by uric acid: mechanisms of inflammation associated with hyperuricemia and its complications

Use of rasburicase to improve kidney function in children with hyperuricemia and acute kidney injury

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