title: Low Protein A20 in Minor Salivary Glands is Associated with Lymphoma in Primary Sjögren's Syndrome.
abstract: Patients with primary Sjögren's syndrome (pSS) have an increased risk of developing lymphomas, particularly the subtype mucosa-associated lymphoid tissue (MALT) lymphoma. Chronic antigen stimulation and increased activation of nuclear factor-κB (NF-κB) are important factors for the pathogenesis of MALT lymphomas. Protein A20 is an inhibitor of NF-κB. A recent study of pSS-associated MALT lymphomas identified potential functional abnormalities in the TNFAIP3 gene, which encodes protein A20. The present study aimed to assess protein A20 by immunohistochemistry (IHC) in minor salivary glands (MSGs) and lymphoma tissue sections of patients with pSS and investigate a potential association with lymphoma development. Protein A20 staining in lymphocytes was scored in four categories (0 = negative, 1 = weak, 2 = moderate and 3 = strong). For statistical purposes, these scores were simplified into negative (scores 0-1) and positive (scores 2-3). We investigated associations between protein A20-staining, focus scores, germinal centre (GC)-like structures and monoclonal B-cell infiltration in MSGs. MSG protein A20 staining was weaker in pSS patients with lymphomas than in those without lymphomas (P = 0.01). Weak protein A20 staining was also highly associated with a lack of GC formation (P < 0.01). Finally, weaker A20 staining was observed in the majority of pSS-associated MALT lymphoma tissues. In conclusion, we found absent or weak protein A20 immunoreactivity in MSGs of patients with pSS with lymphomas. This finding indicates that protein A20 downregulation in lymphocytes might be a mechanism underlying lymphoma genesis in patients with pSS.
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: S J
authors.initials: SJ
authors.lastname: Johnsen
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Gudlaugsson
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: I
authors.initials: I
authors.lastname: Skaland
authors.affiliation: Department of Pathology, Stavanger University Hospital, Stavanger, Norway.
authors.forename: E A M
authors.initials: EA
authors.lastname: Janssen
authors.affiliation: Section for Oral and Maxillofacial Radiology, Department of Clinical Dentistry, University of Bergen, Bergen, Norway.
authors.forename: M V
authors.initials: MV
authors.lastname: Jonsson
authors.affiliation: Department of Pathology, Haukeland University Hospital, Bergen, Norway.
authors.forename: L
authors.initials: L
authors.lastname: Helgeland
authors.affiliation: The Gade Laboratory for Pathology, Department of Clinical Medicine, University of Bergen, Bergen, Norway.
authors.forename: E
authors.initials: E
authors.lastname: Berget
authors.affiliation: Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, Bergen, Norway.|Department of Rheumatology, Haukeland University Hospital, Bergen, Norway.
authors.forename: R
authors.initials: R
authors.lastname: Jonsson
authors.affiliation: Clinical Immunology Unit, Department of Internal Medicine, Stavanger University Hospital, Stavanger, Norway.
authors.forename: R
authors.initials: R
authors.lastname: Omdal
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000378:metabolism*; D005260:Female; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D018442:Lymphoma, B-Cell, Marginal Zone / Q000175:diagnosis / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D012469:Salivary Glands / Q000473:pathology*; D012859:Sjogren's Syndrome / Q000175:diagnosis / Q000453:epidemiology*; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3
chemical_list: D004268:DNA-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; C076529:TNFAIP3 protein, human; D000072598:Tumor Necrosis Factor alpha-Induced Protein 3