Immunization with myelin basic protein (MBP) induces experimental allergic encephalomyelitis (EAE), a prototype of CD4+ T-cell mediated autoimmune disease. In rodents, MBP-reactive T-cell clones are specific for a single, dominant determinant on MBP and use a highly restricted number of T-cell receptor genes. Accordingly, EAE has been prevented by various receptor-specific treatments, suggesting similar strategies may be useful for therapy of human autoimmune disease. Here we report that in (SJL x B10.PL)F1 mice, immune dominance of a single determinant, MBP:Ac1-11, is confined to the inductive phase of EAE. In mice with chronic EAE, several additional determinants of MBP in peptides 35-47, 81-100 and 121-140 recall proliferative responses. Most importantly, reactivity to the latter determinants was also detected after induction of EAE with MBP peptide Ac1-11 alone; this demonstrates priming by endogenous MBP determinants. Thus, determinants of MBP that are cryptic after primary immunization can become immunogenic in the course of EAE. Diversification of the autoreactive T-cell repertoire due to 'determinant spreading' has major implications for the pathogenesis of, and the therapeutic approach to, T-cell driven autoimmune disease.

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BackgroundThe heterogeneous behavior of patients with melanoma makes prognostication challenging. To address this, a gene expression profile (GEP) test to predict metastatic risk was previously developed. This study evaluates the GEP’s prognostic accuracy in an independent cohort of cutaneous melanoma patients.MethodsThis multi-center study analyzed primary melanoma tumors from 523 patients, using the GEP to classify patients as Class 1 (low risk) and Class 2 (high risk). Molecular classification was correlated to clinical outcome and assessed along with AJCC v7 staging criteria. Primary endpoints were recurrence-free (RFS) and distant metastasis-free (DMFS) survival.ResultsThe 5-year RFS rates for Class 1 and Class 2 were 88% and 52%, respectively, and DMFS rates were 93% versus 60%, respectively (P < 0.001). The GEP was a significant predictor of RFS and DMFS in univariate analysis (hazard ratio [HR] = 5.4 and 6.6, respectively, P < 0.001 for each), along with Breslow thickness, ulceration, mitotic rate, and sentinel lymph node (SLN) status (P < 0.001 for each). GEP, tumor thickness and SLN status were significant predictors of RFS and DMFS in a multivariate model that also included ulceration and mitotic rate (RFS HR = 2.1, 1.2, and 2.5, respectively, P < 0.001 for each; and DMFS HR = 2.7, 1.3 and 3.0, respectively, P < 0.01 for each).ConclusionsThe GEP test is an objective predictor of metastatic risk and provides additional independent prognostic information to traditional staging to help estimate an individual’s risk for recurrence. The assay identified 70% of stage I and II patients who ultimately developed distant metastasis. Its role in consideration of patients for adjuvant therapy should be examined prospectively.Electronic supplementary materialThe online version of this article (10.1186/s12885-018-4016-3) contains supplementary material, which is available to authorized users.

Objective-The study evaluated the association of religiosity/spirituality (R/S) and health-related quality of life (HRQOL) among Latina breast cancer survivors (BCS) in order to determine whether R/S would be positively correlated with HRQOL and whether R/S would significantly influence HRQOL. Methods-The cross-sectional study utilized self-report data from 117 Latina BCS survivors. R/ S was measured with the Systems of Belief Inventory -15 Revised (SBI-15R) and HRQOL was measured with the Functional Assessment of Cancer Therapy -General (FACT-G). Analyses included calculation of descriptive statistics, t-tests, bivariate correlations, and multivariate analyses.Results-Latina BCS had very high levels of R/S and generally good HRQOL. The SBI-15R total score was positively correlated with FACT-G social well-being (r=0.266, p=0.005), relationship with doctor (r=0.219, p=0.020), and functional well-being (r=0.216, p=0.022). Multivariate analyses revealed that SBI-15R was a significant predictor of FACT-G functional well-being (p=0.041) and satisfaction with the relationship with the doctor (p=0.050), where higher levels of R/S predicted higher levels of well-being.Conclusions-Latina BCS had very high levels of R/S, which were significantly, positively correlated with dimensions of HRQOL (social well-being, functional well-being, relationship with doctor). Further, these high levels of R/S predicted better functional well-being and satisfaction with the patient-doctor relationship while controlling for potentially confounding variables. Implications are discussed.