Clinical Study of the Relationship between Sjögren Syndrome and T-Cell Large Granular Lymphocytic Leukemia: Single-Center Experience (original) (raw)
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Cancers, 2020
STAT3 and STAT5B (STAT3/STAT5B) mutations are the most common mutations in T-cell large granular lymphocytic leukemia (T-LGLL) and chronic lymphoproliferative disorders of NK cells (CLPD-NK), but their clinical impact remains unknown. We investigated the frequency and type of STAT3/STAT5B mutations in FACS-sorted populations of expanded T/NK-LGL from 100 (82 clonal; 6 oligoclonal; 12 polyclonal) patients, and its relationship with disease features. Seventeen non-LGL T-CLPD patients and 628 age-matched healthy donors were analyzed as controls. STAT3 (n = 30) and STAT5B (n = 1) mutations were detected in 28/82 clonal T/NK-LGLL patients (34%), while absent (0/18, 0%) among oligoclonal/polyclonal LGL-lymphocytosis. Mutations were found across all diagnostic subgroups: TCD8+-LGLL, 36%; CLPD-NK, 38%; TCD4+-LGLL, 7%; Tαβ+DP-LGLL, 100%; Tαβ+DN-LGLL, 50%; Tγδ+-LGLL, 44%. STAT3-mutated T-LGLL/CLPD-NK showed overall reduced (p < 0.05) blood counts of most normal leukocyte subsets, with a hi...
Clinical Reviews in Allergy & Immunology, 2007
Among autoimmune diseases, Sjogren's syndrome (SS) displays the highest incidence of non-Hodgkin lymphoma (NHL) development with the salivary extranodal marginal zone B cell lymphomas being the most common type. The majority of SS-associated NHLs are characterized by localized stage, indolent clinical course, and recurrence in other extranodal sites. Although the transition from a chronic inflammatory condition to malignant lymphoma is a multistep process yet poorly understood, there is increasing evidence that chronic antigenic stimulation by an exoantigen or autoantigens plays an essential role in the development of SS associated lymphoproliferation. Additional molecular oncogenic events such as microsatellite instability, loss of the B cell cycle control, and the forced overproduction of specific B cell biologic stimulators seem to contribute to the emergence and progression of the malignant overgrowth. Among the clinical and serological parameters that have been associated with lymphoma development in SS patients, the presence of palpable purpura, low C4, and mixed monoclonal cryoglobulinemia constitute the main predictive markers, and patients displaying these risk factors should be monitored closely.
Journal of Clinical Medicine, 2021
Background: Primary Sjogren’s syndrome (SS) is an autoimmune disease with a strong predilection for lymphoma development, with earlier disease onset being postulated as an independent risk factor for this complication. Variations of the Leukocyte immunoglobulin-like receptor A3(LILRA3) gene have been previously shown to increase susceptibility for both SS and non-Hodgkin B-cell lymphoma (B-NHL) in the general population. We aimed to investigate whether variations of the LILRA3 gene could predispose for lymphoma development in the context of SS. Methods: Study population, all of Greek origin, included 101 SS cases with a current or previous diagnosis of lymphoma (SS-lymphoma, SS-L) and 301 primary SS patients not complicated by lymphoma (SS-non-lymphoma, SS-nL). All SS patients fulfilled the 2016 SS American College of Rheumatology/European league against Rheumatism (ACR/EULAR) classification criteria. A total of 381 healthy controls (HC) of similar age/sex/race distribution were als...
Predictors for the development of non-Hodgkin lymphoma in primary Sjögren's syndrome
Presse médicale (Paris, France : 1983), 2012
Sjögren's syndrome (SS) is a complex autoimmune disease with multi-organ involvement. Its most serious complication is the development of non-Hodgkin lymphoma (NHL). In cohorts of unselected patients with long observation, this lifetime risk is estimated to be 5 to 15%, or approximately 20 times increased risk compared to the general population. Being able to identify patients prone to malignancy would significantly aid in the process of customised treatment and strategy for follow-up. Among the established predictors for lymphoma development in SS, we recognize recurrent or permanent swelling of major salivary glands (SG), lymphadenopathy, cryoglobulinemia, splenomegaly, low complement levels of C4 and C3, lymphopenia, skin vasculitis or palpable purpura, M-component in serum or urine, peripheral neuropathy, glomerulonephritis and elevated beta2-microglobulin. More recent suggestions include some genetic factors, CD4 lymphocytopenia, and ectopic germinal center-like structures ...
Cancer causes & control : CCC, 1997
The risk of hematologic malignancies was studied in Finnish patients with rheumatoid arthritis or Sjögren's syndrome, and the difference in the risk between those diseases was evaluated. The study cohorts comprised 676 patients with primary Sjögren's syndrome, 709 with secondary Sjögren's syndrome, and 9,469 with rheumatoid arthritis identified from the Finnish hospitals' national discharge register. The follow-up times were 5,336, 4,254 and 65,391 person-years, respectively. Data on the incidence of malignancies were collected from the files of the Finnish Cancer Registry. The incidence of hematologic malignancies was elevated in the study cohorts. The standardized incidence ratio (SIR) of non-Hodgkin's lymphoma was: 2.2 (95 percent confidence interval [CI] 1.5-3.1) for rheumatoid arthritis; 4.5 (CI = 1.5-11) for secondary Sjögren's syndrome; and 8.7 (CI = 4.3-16) for primary Sjögren's syndrome. The ratio of the SIR of primary Sjögren's syndrome cf r...
Development of lymphoma in patients with primary Sjögren syndromes
International Journal of Clinical Rheumatology, 2019
Background: Lymphoma is the main complication of primary Sjögren syndrome (pSS). The aim of this study was to describe the prevalence and incidence rate of lymphoma in patients with pSS in eleven centers in Argentina. To determine the frequency of commitment of the domains of the baseline clinical ESSDAI in the patients who developed lymphoma in the course of their follow-up and compare it with the rest of the sample. Methods and findings: We included patients older than 18 years with a diagnosis of pSS according to American College of Rheumatology/European League against Rheumatism (ACR/EULAR)2002/2016 criteria, included in a multi-center Argentine database. Patients diagnosed with another associated autoimmune rheumatic disease were excluded. Six hundred and eighty one patients were included, 95% female, with a mean age of 54.41 years (± 13.70). Sixteen patients presented lymphoma (prevalence: 2.35%, 95% CI: 1.2-3.4%). The average follow-up time was 4.7 years (± 4.94). Six hundread and thirty three patients contributed data for the survival analysis. The incidence rate of lymphoma was 0.54 per 100 patient-years (95% CI:-0,26 a 1,34). The most frequently lymphoma type was MALT. Patients who developed lymphoma had a higher frequency of involvement of most of the domains of the baseline clinical ESSDAI compared to patients who did not present this complication, observing statistically significant differences in glandular (68,75% vs 28.69%, p:0,001), and cutaneous (31.25% vs 10.99%, p: 0.01) domains. The glandular domain of clinical ESSDAI was the main domain associated lymphoma development (H.R: 4.54, 95% CI: 1.57-13.12). Conclusion: This was the first study with data on the population of Argentina about the prevalence of lymphoma in patients diagnosed with Sjogren's syndrome. The prevalence of lymphoma in our cohort was lower than previously published. Despite observing a lower frequency of lymphoma in our study, we found an association with risk markers described in the literature, such as baseline parotidomegaly and cutaneous involvement.
Rheumatology, 2021
The intrinsic and complex nature of primary Sjӧgren's syndrome (pSS) makes it difficult to identify risk factors that can predict the development and outcome of non-Hodgkin's lymphoma (NHL), yet patients at high risk for such complication seem to bear certain clinic-serological characteristics that render them a unique profile. In the last decade, research focusing on B-cell hyperactivity as the hallmark of pSS-related lymphoproliferation has shed light on certain biological and molecular factors that participate in disease evolution and lymphoma development, thus indicating possible predictors of lymphoma development and outcome. In this review, we explore all the available data concerning the clinical picture, risk prognostication and outcome of pSS-associated NHLs.
Somatic STAT3 Mutations in Large Granular Lymphocytic Leukemia
New England Journal of Medicine, 2012
BACKGROUND T-cell large granular lymphocytic leukemia is a rare lymphoproliferative disorder characterized by the expansion of clonal CD3+CD8+ cytotoxic T lymphocytes (CTLs) and often associated with autoimmune disorders and immune-mediated cytopenias.
Lymphoma and Lymphomagenesis in Primary Sjögren's Syndrome
Frontiers in medicine, 2018
Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease mainly affecting exocrine glands and leading to impaired secretory function. The clinical picture is dominated by signs and symptoms of mucosal dryness and the course of the disease is mild and indolent in the majority of cases. However, a subgroup of patients can also experience extraglandular manifestations that worsen the disease prognosis. pSS patients are consistently found to have a higher risk of developing non-Hodgkin lymphoma (NHL) compared with patients with other autimmune disorders and to the general population. NHL is the most severe comorbidity that can occur in pSS, therefore recent research has aimed to identify reliable clinical, serological, and histological biomarkers able to predict NHL development in these subjects. This review article encompasses the body of evidence published so far in this field highlighting the challenges and pitfalls of different biomarkers within clinical practice. We al...