Predicting adverse outcomes in primary Sjogren's syndrome: identification of prognostic factors
ABSTRACT To identify features present at diagnosis that were prospectively associated with adverse outcomes in a large cohort of patients with primary Sjögren's syndrome (SS).
Two hundred and sixty-six patients diagnosed with primary SS in our department between 1984 and 2002 were consecutively included and followed up. Outcomes measured were vasculitis, B-cell lymphoma and death. Cox regression analysis was used to evaluate the effect of variables at diagnosis on outcomes.
Twenty-five (9%) patients developed vasculitis. Multivariate analysis identified parotid scintigraphy grades III or IV (HR 3.55, P = 0.05) and C4 levels <0.11 g/l (HR 8.26, P < 0.001) as variables predicting the development of vasculitis. Nine (3%) patients developed B-cell lymphoma. Multivariate analysis identified C3 levels <0.82 g/l (HR 7.54, P = 0.016) as a predictive factor of lymphoma development. Twenty-five (9%) patients died during follow-up. Systemic involvement (HR 4.51, P = 0.022), vasculitis (HR 4.58, P = 0.042), C4 levels <0.11 g/l (HR 5.47, P = 0.027) and cryoglobulins (HR 4.58, P = 0.013) were independently associated with death. The presence of at least two of the above-mentioned predictive factors (parotid scintigraphy, vasculitis, hypocomplementaemia and cryoglobulinaemia) was associated with a lower survival in comparison with patients with no factor (log rank and Breslow tests <0.001).
The main prognostic factors for an adverse outcome identified in our cohort of patients with primary SS were vasculitis, severe involvement in parotid scintigraphy, hypocomplementaemia and/or cryoglobulins at diagnosis. Patients with at least two of these factors need a closer follow-up.
SourceAvailable from: Vartolomei Mihai Dorin
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ABSTRACT: Autoimmune conditions and immune system-related genetic variations are associated with risk of non-Hodgkin lymphoma (NHL). In a pooled analysis of 8,692 NHL cases and 9,260 controls from 14 studies (1988-2007) within the International Lymphoma Epidemiology Consortium, we evaluated the interaction between immune system genetic variants and autoimmune conditions in NHL risk. We evaluated the immunity-related single nucleotide polymorphisms rs1800629 (tumor necrosis factor gene (TNF) G308A), rs1800890 (interleukin-10 gene (IL10) T3575A), rs6457327 (human leukocyte antigen gene (HLA) class I), rs10484561 (HLA class II), and rs2647012 (HLA class II)) and categorized autoimmune conditions as primarily mediated by B-cell or T-cell responses. We constructed unconditional logistic regression models to measure associations between autoimmune conditions and NHL with stratification by genotype. Autoimmune conditions mediated by B-cell responses were associated with increased NHL risk, specifically diffuse large B-cell lymphoma (odds ratio (OR) = 3.11, 95% confidence interval (CI): 2.25, 4.30) and marginal zone lymphoma (OR = 5.80, 95% CI: 3.82, 8.80); those mediated by T-cell responses were associated with peripheral T-cell lymphoma (OR = 2.14, 95% CI: 1.35, 3.38). In the presence of the rs1800629 AG/AA genotype, B-cell-mediated autoimmune conditions increased NHL risk (OR = 3.27, 95% CI: 2.07, 5.16; P-interaction = 0.03) in comparison with the GG genotype (OR = 1.82, 95% CI: 1.31, 2.53). This interaction was consistent across major B-cell NHL subtypes, including marginal zone lymphoma (P-interaction = 0.02) and follicular lymphoma (P-interaction = 0.04). © The Author 2015. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: firstname.lastname@example.org.
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ABSTRACT: Non-Hodgkin's lymphoma (NHL) development in Sjögren's syndrome (SS) remains a potentially lethal complication and efforts should focus on the identification of predictors that could aid in appropriate therapeutic decisions. In order to identify potential prognostic factors for outcome in SS-associated NHL, we retrospectively analyzed a cohort of 77 patients, diagnosed with NHL according to WHO classification criteria and meeting the American-European Consensus Classification (AECC) criteria for SS and examined the effect of SS-activity (defined as the EULAR SS disease activity index-ESSDAI) in the prognosis of SS-related NHLs, as defined in terms of overall and event-free survivals (OS and EFS). An event was defined as lymphoma relapse, treatment failure, disease progression, histological transformation or death. The effect of NHL clinical and laboratory characteristics was also investigated. MALT lymphomas constituted the majority (66.2%) of lymphomas. During the follow-up (median = 57.93 months), the 5-year OS was 90.91% (95% CI: 82.14-95.80%) and the EFS was 77.92% (95% CI: 67.37-85.82%). Patients with high ESSDAI score at lymphoma diagnosis had a greater risk for death (OR = 5.241, 95% CI: 1.034-26.568) or for event (OR = 4.317, 95% CI: 1.146-9.699, p = 0.008). These patients had also significantly worse EFS (HR = 4.541, 95% CI: 1.772-11.637) and OS (HR = 5.946, 95% CI: 1.259-28.077). In addition, post-chemotherapy ESSDAI improvement was significantly lower in patients who had experienced an event (p = 0.005). An unfavorable International prognostic index (IPI) score (high-intermediate/high) was associated with high risk of death and event (OR = 13.867, 95% CI: 2.656-72.387 and OR = 12.589, 95% CI: 3.911-40.526, respectively), worse EFS (log-rank p<0.001, HR = 8.718, 95% CI: 3.477-21.858), as well as with worse OS (log-rank p<0.001, HR = 11.414, 95% CI: 2.414-53.974). After adjustment for identified risk factors, IPI score retained a significant prognostic role following by a strong effect of ESSDAI in survival outcomes. At the point of NHL diagnosis, IPI and ESSDAI might be proved useful predictive tools in SS-associated lymphoma prognosis, directing to a more patient-tailored approach.PLoS ONE 02/2015; 10(2):e0116189. DOI:10.1371/journal.pone.0116189 · 3.53 Impact Factor