Sjögren Syndrome-associated lymphomas: an update on pathogenesis and management

Br J Haematol. 2015 Feb;168(3):317-27. doi: 10.1111/bjh.13192. Epub 2014 Oct 15.


Primary Sjögren Syndrome (pSS) is an autoimmune disease associated with an increased risk of lymphoma. Lymphomas complicating pSS are mostly low-grade B cell non-Hodgkin lymphomas, predominantly of marginal zone histological type. Mucosal localization is predominant, notably mucosa-associated lymphoid tissue lymphomas. Lymphomas often develop in organs where pSS is active, such as salivary glands. Germinal centre (GC)-like structures, high TNFSF13B (BAFF) and Flt3-ligand (FLT3LG) levels and genetic impairment of TNFAIP3 are new predictors of lymphoma development. These new findings allow a better understanding of the pathogenic mechanisms leading to lymphoma. We propose the following scenario: auto-immune B cells with rheumatoid factor (RF) activity are continuously stimulated by immune complexes containing antibodies against more specific auto-antigens, such as SSA/Ro, SSB/La or others. Germline abnormality of TNFAIP3 leads to a decreased control of the NF-kB pathway and thus promotes survival of B cells and oncogenic mutations especially in GC structure. Moreover, B cells are stimulated by a positive loop of activation induced by BAFF secretion. Thus, lymphomagenesis associated with pSS exemplifies the development of antigen-driven B-cell lymphoma. The control of disease activity by a well-targeted immunosuppressor is the primary objective of the management of the patient in order to repress chronic B cell stimulation.

Keywords: NF-kB; Sjögren syndrome; auto-immunity; lymphomagenesis; mucosa-associated lymphoid tissue lymphoma.

Publication types

  • Review

MeSH terms

  • Cell Transformation, Neoplastic / immunology
  • Hepatitis C, Chronic / complications
  • Humans
  • Lymphoma, B-Cell, Marginal Zone / epidemiology
  • Lymphoma, B-Cell, Marginal Zone / etiology*
  • Lymphoma, B-Cell, Marginal Zone / therapy
  • Risk Factors
  • Sjogren's Syndrome / complications*
  • Sjogren's Syndrome / epidemiology
  • Sjogren's Syndrome / immunology