title: Sjögren Syndrome-associated lymphomas: an update on pathogenesis and management.
abstract: 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.
authors.affiliation: INSERM U1012, Paris-Sud University, Le Kremlin-Bicêtre, France.
authors.forename: Gaetane
authors.initials: G
authors.lastname: Nocturne
authors.forename: Xavier
authors.initials: X
authors.lastname: Mariette
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000276:immunology; D019698:Hepatitis C, Chronic / Q000150:complications; D006801:Humans; D018442:Lymphoma, B-Cell, Marginal Zone / Q000453:epidemiology / Q000209:etiology* / Q000628:therapy; D012307:Risk Factors; D012859:Sjogren's Syndrome / Q000150:complications* / Q000453:epidemiology / Q000276:immunology
keywords: NF-kB; Sjögren syndrome; auto-immunity; lymphomagenesis; mucosa-associated lymphoid tissue lymphoma