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  • Review Article
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B-cell lymphoproliferation in chronic inflammatory rheumatic diseases

Nature Clinical Practice Rheumatology volume 3, pages 561–569 (2007)Cite this article

Abstract

Patients with chronic inflammatory rheumatic diseases, such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and especially primary Sjögren's syndrome (SS), are at higher risk than the general population of developing B-cell non-Hodgkin lymphoma (NHL). Analyses of the association between various lymphoma subtypes and specific disease entities suggest that this association might be mediated by disease-specific mechanisms, as well as by mechanisms unique to lymphoma subtype. These specific associations can provide important information about abnormal B-cell stimulation in these conditions. Patients with primary SS, SLE and RA are at high risk of developing diffuse large B-cell lymphomas, a group of high-grade NHLs with remarkable heterogeneity. Patients with primary SS are at particularly high risk of developing marginal-zone B-cell lymphomas. The risk factors of lymphoma development in primary SS seem to be closely related to the underlying mechanisms of abnormal stimulation and/or impaired censoring mechanisms of B cells. In patients with RA and SLE, more intense disease activity and/or long-lasting disease might be indications of a higher risk of lymphoma development. This Review will focus on the risk of lymphoma, common and disease-specific mechanisms of B-cell lymphoma development, and on the clinical consequences of lymphoma in patients with inflammatory rheumatic diseases.

Key Points

  • Patients with primary Sjögren's syndrome (SS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) are at an increased risk of developing B-cell lymphomas, with the highest risk in patients with primary SS

  • Prevalence of lymphoma subtypes in patients with primary SS, SLE and RA might partly reflect underlying disease-specific mechanisms of abnormal B-cell activation

  • There are strong indications that many of these B-cell lymphomas depend on antigen binding and/or their local microenvironment, apart from the accumulation of molecular oncogenic lesions

  • In primary SS, clinicopathological risk factors have been identified that allow identification of patients who are at an increased risk of developing B-cell lymphoma and, therefore, warrant careful follow-up

  • Progress in B-cell targeted therapies, in particular by B-cell depletion with rituximab, markedly improves the therapeutic options for indolent and aggressive B-cell lymphomas

  • The clinical benefits resulting from B-cell depletion therapy further illustrate the pivotal role of B cells in the immunopathogenesis of inflammatory rheumatic diseases

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Figure 1: B-cell lymphoma subtypes associated with chronic inflammatory rheumatic diseases: postulated cellular origin and the influences on their malignant phenotype.

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Acknowledgements

This work was supported by Deutsche Forschungsgemeinschaft Grant Do 491/4-7.

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Authors and Affiliations

  1. A Hansen is Assistant Professor and Senior Physician at the Outpatients Department of Medicine, and T Dörner is Professor of Medicine in the Division of Clinical Hemostaseology, both at the Charité University Hospital, Berlin, Germany.,

    Arne Hansen & Thomas Dörner

  2. PE Lipsky is the Editor-in-Chief of Nature Clinical Practice Rheumatology.,

    Peter E Lipsky

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Correspondence to Arne Hansen.

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Hansen, A., Lipsky, P. & Dörner, T. B-cell lymphoproliferation in chronic inflammatory rheumatic diseases. Nat Rev Rheumatol 3, 561–569 (2007). https://doi.org/10.1038/ncprheum0620

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