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Effects of rituximab therapy on B cell differentiation and depletion

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Abstract

Rituximab is a human/murine chimeric anti-CD20 monoclonal antibody. It is largely used to treat B cell malignancies and has become standard in the management of B cell‑mediated diseases such as rheumatoid arthritis and granulomatosis with polyangitis. The effects of rituximab need to be monitored by B cell phenotyping. Evaluate possible surface markers for monitoring B cell development in response to rituximab treatment. This review discusses the literature on the B cell surface markers analysed by flow cytometry in patients treated with rituximab. A panel of biomarkers of response to treatment to monitor by flow cytometry is also suggested. B cell phenotyping is useful to predict clinical relapses after rituximab treatment. The proposed panel of biomarkers includes CD38++CD24++IgD+/− immature B cells and IgD−CD38+/− memory B cells. In responders, Th1/Th2 balance and tolerance cells (CD4+CD25+CD127−/low Treg cells and CD19+CD24hiCD38hi Breg cells) tend to be restored after rituximab therapy. Furthermore, in responder patients, indirect depletion of CD19+/-CD27++CD38++ preplasma cells can be proposed as a predictor of response. Flow cytometric analysis of samples from patients treated with rituximab is a useful strategy to stratify patients according to response to treatment. Identification of B cell differentiation stages by means of a specific flow cytometry panel could improve monitoring of rituximab effects and enable non-responders to be distinguished from good responders.

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Abbreviations

CD:

Cluster of differentiation

NHLs:

Non-Hodgkin lymphomas

CLL:

Chronic lymphocytic leukemia

mAb:

Monoclonal antibody

CDC:

Complement-dependent cytotoxicity

ADCC:

Antibody-dependent cellular cytotoxicity

Fc:

Fragment crystallizable

Ig:

Immunoglobulin

GC cells:

Germinal center cells

TNF:

Tumor necrosis factor

Th:

T helper

NK:

Natural killer

NKT-like:

Natural killer T cells

Breg:

Regulatory B cells

TGF:

Transforming growth factor

INF:

Interferon

IL:

Interleukin

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Acknowledgments

The present work was performed at Siena University.

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Authors and Affiliations

  1. Department of Medical Sciences, Surgery and Neurosciences. Respiratory Diseases and Lung Transplant Unit, Siena University, 53100, Siena, Italy

    L. Bergantini, M. d’Alessandro, P. Cameli, L. Vietri, C. Vagaggini, A. Perrone, P. Sestini & E. Bargagli

  2. Research Center of Systemic Autoinflammatory Diseases and Behçet’s Disease and Rheumatology-Ophthalmology Collaborative Uveitis Center, Department of Medical Sciences, Surgery and Neurosciences, University of Siena, Siena, Italy

    B. Frediani

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LB had the idea for the article, LB PC LV CV AP literature search, LB PC Md data analysis, LB Md drafted the work and EB BF PS critically revised the work.

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Bergantini, L., d’Alessandro, M., Cameli, P. et al. Effects of rituximab therapy on B cell differentiation and depletion. Clin Rheumatol 39, 1415–1421 (2020). https://doi.org/10.1007/s10067-020-04996-7

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