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.