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Low Protein A20 in Minor Salivary Glands is Associated with Lymphoma in Primary Sjögren's Syndrome
Author(s) -
Johnsen S. J.,
Gudlaugsson E.,
Skaland I.,
Janssen E. A. M.,
Jonsson M. V.,
Helgeland L.,
Berget E.,
Jonsson R.,
Omdal R.
Publication year - 2016
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12405
Subject(s) - lymphoma , malt lymphoma , immunohistochemistry , pathology , staining , pathogenesis , germinal center , downregulation and upregulation , salivary gland , medicine , biology , antibody , immunology , b cell , gene , biochemistry
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‐ κ B ( NF ‐ κ B) are important factors for the pathogenesis of MALT lymphomas. Protein A20 is an inhibitor of NF ‐ κ B. A recent study of pSS ‐associated MALT lymphomas identified potential functional abnormalities in the TNFAIP 3 gene, which encodes protein A20. The present study aimed to assess protein A20 by immunohistochemistry ( IHC ) in minor salivary glands ( MSG s) 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 MSG s. 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 MSG s 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 .