Lymphoproliferative disorders in Sjögren's syndrome

Yasukawa, Masaki; Sugai, Susumu

doi:10.1016/s1568-9972(03)00102-2

Cited by 129 publications

(98 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[55][56][57] It is in fact well established that in certain autoimmune diseases, especially in Sjögren syndrome, there is a strong association with lymphoma, and in particular with MZL. [58][59][60] This is thought to occur due to constant activation of B cells, which in turn increases the probability of lymphoma development. If this would be the case in Aire Ϫ/Ϫ mice, it must be an indirect effect, since Aire is not expressed in B cells.…”

Section: Discussionmentioning

confidence: 99%

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma

Hässler

Ramsey

Karlsson

et al. 2006

Blood

View full text Add to dashboard Cite

Autoimmune polyendocrine syndrome type I (APS I) is an inherited recessive disorder with a progressive immunological destruction of many tissues including the adrenal cortex, the parathyroid glands, and the gonads. APS I is caused by mutations in the AIRE gene (autoimmune regulator), expressed in cells of the thymus and spleen, suggesting a role in central and peripheral tolerance. Aire ؊/؊ mice replicate the autoimmune features of APS I patients with the presence of multiple autoantibodies and lymphocytic infiltrates in various tissues, but young mice appear clinically healthy. We here report the investigation of 15-to 24-monthold Aire ؊/؊ mice. We did not observe any endocrinological abnormalities, nor did sera from these mice recognize known APS I autoantigens. Interestingly, however, there was a high frequency of marginal zone B-cell lymphoma in Aire ؊/؊ mice and liver infiltrates of B cells, suggesting chronic antigen exposure and exaggerated activation. Furthermore, increased numbers of monocytes in blood were identified as well as augmented numbers of metallophilic macrophages in the spleen. We propose that Aire, in addition to its function in the thymus, also has a peripheral regulatory role by controlling the development of antigen-presenting cells ( IntroductionIn autoimmune polyendocrine syndrome type I 1 (APS I, or autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy [APECED]; Online Mendelian Inheritance in Man [OMIM] no. 240300), an inherited autoimmune disorder without major histocompatibility complex (MHC) linkage, 2,3 patients progressively lose tolerance to various tissue-specific antigens, with ensuing endocrine and nonendocrine disorders. APS I patients suffer from multiple organ failures due to immunologic destruction of the adrenal cortex, the parathyroid glands, the liver, ␤-cells of the islets of Langerhans, and enterochromaffin cells of the small intestine. In addition, probably as a sign of immune dysfunction, the patients suffer from a chronic mucocutaneous candidiasis. 1 The prevalence of APS I is increased in Finland, Sardinia, and among Iranian Jews. [4][5][6] The disease-causing gene was localized to the long arm of chromosome 21 7 and has later been identified and named the autoimmune regulator (AIRE). 8,9 AIRE has been proposed to function as a transcription factor. [10][11][12][13][14] Aire is expressed in thymic medullary epithelial cells, in dendritic cells, [15][16][17][18] and in blood monocytes, 19 suggesting a role of Aire in both central and peripheral tolerance. To define the role of Aire in immunologic tolerance, we previously reported an Aire Ϫ/Ϫ mouse line engineered to reproduce the most common Finnish APS I mutation. 20 In analogy with APS I, Aire Ϫ/Ϫ mice display multiple organ-specific autoantibodies and lymphocytic infiltrates. 20,21 Since Aire is expressed in medullary epithelial cells of the thymus (mTEC), studies have so far focused on central tolerance and have addressed the role of Aire in negative selection. 21,22 Aire has been proposed to ac...

show abstract

Section: Discussionmentioning

confidence: 99%

Aire-deficient mice develop hematopoetic irregularities and marginal zone B-cell lymphoma

Hässler

Ramsey

Karlsson

et al. 2006

Blood

View full text Add to dashboard Cite

show abstract

“…Further US monitoring for early detection of possible lymphomatous change is required in patients with Sjö gren syndrome (63,64). Biopsy is recommended for lesions exceeding 2 cm or fast-growing lesions (9).…”

Section: Sjö Gren Syndromementioning

confidence: 99%

“…Clinically, salivary lymphomas most often manifest as a painless, progressive swelling (107,108). They are usually associated with autoimmune disease, most often with Sjö gren syndrome, sometimes also with rheumatoid arthritis (62)(63)(64)109).…”

Section: Lymphomamentioning

confidence: 99%

US of the Major Salivary Glands: Anatomy and Spatial Relationships, Pathologic Conditions, and Pitfalls

Białek¹,

Jakubowski²,

Zajkowski³

et al. 2006

RadioGraphics

256

242

View full text Add to dashboard Cite

“…Lymphoma can present as a background of chronic inflammation. In SS, antigenic activation of B cells, together with oncogenic events, including p53 inactivation and bcl-2 activation, may play important roles in B cell monoclonal proliferation and malignant transformation (12). It is reported that the SIR for lymphoma in patients with SS was higher, 8.7 to 48.1 (13)(14)(15).…”

Section: Igg4-related Disease and Malignancymentioning

confidence: 99%