B Cell Therapy in Systemic Lupus Erythematosus: From Rationale to Clinical Practice

Frontiers in Medicine

article

Ioannis Parodis¹  Marit Stockfelt³  Christopher Sjöwall⁴ 

[1] Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet;Karolinska University Hospital;Department of Rheumatology and Inflammation Research, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg;Division of Inflammation and Infection, Department of Biomedical and Clinical Sciences, Linköping University

关键词: B cells;    systemic lupus erythematosus;    therapy;    biologics;    plasma cells;    plasmablasts;    lupus nephritis;   

DOI  :  10.3389/fmed.2020.00316

学科分类：社会科学、人文和艺术（综合）

来源: Frontiers

【 摘 要 】

B cell hyperactivity and breach of tolerance constitute hallmarks of systemic lupus erythematosus (SLE). The heterogeneity of disease manifestations and relatively rare prevalence of SLE have posed difficulties in trial design and contributed to a slow pace for drug development. The anti-BAFF monoclonal antibody belimumab is still the sole targeted therapy licensed for SLE, lending credence to the widely accepted notion that B cells play central roles in lupus pathogenesis. However, more therapeutic agents directed toward B cells or B cell-related pathways are used off-label or have been trialed in SLE. The anti-CD20 monoclonal antibody rituximab has been used to treat refractory SLE during the last two decades, and the anti-type I IFN receptor anifrolumab is currently awaiting approval after one phase III clinical trial which met its primary endpoint and one phase III trial which met key secondary endpoints. While the latter does not directly affect the maturation and antibody production activity of B cells, it is expected to affect the contribution of B cells in proinflammatory cytokine excretion. The proteasome inhibitor bortezomib, primarily directed toward the plasma cells, has been used in few severe cases as an escape regimen. Collectively, current clinical experience and primary results of ongoing clinical trials prophesy that B cell therapies of selective targets will have an established place in the future personalized therapeutic management of lupus patients.

【 授权许可】

CC BY