المؤلفون: Caballero, Noe, Machiraju, Siddharth, Diomino, Anthony, Kennedy, Leda, Kadivar, Armita, Cadenhead, Kristin

المصدر: Current Psychiatry Reports. 25(11)

مصطلحات موضوعية: Biomarkers, Clinical high risk, Conversion, Prodome, Psychosis, Treatment

الوصف: PURPOSE OF REVIEW: This review highlights recent advances in the prediction and treatment of psychotic conversion. Over the past 25 years, research into the prodromal phase of psychotic illness has expanded with the promise of early identification of individuals at clinical high risk (CHR) for psychosis who are likely to convert to psychosis. RECENT FINDINGS: Meta-analyses highlight conversion rates between 20 and 30% within 2-3 years using existing clinical criteria while research into more specific risk factors, biomarkers, and refinement of psychosis risk calculators has exploded, improving our ability to predict psychotic conversion with greater accuracy. Recent studies highlight risk factors and biomarkers likely to contribute to earlier identification and provide insight into neurodevelopmental abnormalities, CHR subtypes, and interventions that can target specific risk profiles linked to neural mechanisms. Ongoing initiatives that assess longer-term (> 5-10 years) outcome of CHR participants can provide valuable information about predictors of later conversion and diagnostic outcomes while large-scale international biomarker studies provide hope for precision intervention that will alter the course of early psychosis globally.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4mr3h5rmTest

المؤلفون: Arger, Nicholas K, Machiraju, Siddharth, Allen, Isabel E, Woodruff, Prescott G, Koth, Laura L

مصطلحات موضوعية: Lung, Bronchoalveolar Lavage Fluid, Humans, Sarcoidosis, Pulmonary, T-Box Domain Proteins, Prognosis, Case-Control Studies, Adult, Aged, Middle Aged, Female, Male, Interferon-gamma, Nuclear Receptor Subfamily 1, Group F, Member 3, Th17 Cells, Biomarkers, RORγt, T-bet, Th1, Th17, Th17.1, chemokine, interferon-gamma, sarcoidosis, Autoimmune Disease, Clinical Research, 2.1 Biological and endogenous factors, Aetiology, Inflammatory and immune system, 1, ROR gamma t, Immunology, Medical Microbiology

الوصف: Background: Interferon-gamma (IFN-γ) is a key mediator of sarcoidosis-related granulomatous inflammation. Previous findings of IFN-γ-producing Th17 cells in bronchoalveolar lavage fluid from sarcoidosis patients invokes the transition of Th17.0 cells to Th17.1 cells in the disease's pathogenesis. Since the T-bet transcription factor is crucial for this transition, the goal of this study was to determine if T-bet expression in Th17.0 cells reflects the extent of granulomatous inflammation in sarcoidosis patients as assessed by clinical outcomes. Methods: Using a case-control study design, we identified two groups of sarcoidosis subjects (total N = 43) with pulmonary function tests (PFTs) that either (1) changed (increased or decreased) longitudinally or (2) were stable. We used flow cytometry to measure the transcription factors T-bet and RORγt in Th1, Th17.0, and Th17.1 cell subsets defined by CCR6, CCR4 and CXCR3 in blood samples. We compared the percentages of T-bet+ cells in RORγt+Th17.0 cells (defined as CCR6+CCR4+CXCR3-) based on subjects' PFT group. We also assessed the relationship between the direction of change in PFTs with the changes in %T-bet+ frequencies using mixed effects modeling. Results: We found that T-bet expression in subjects' RORγt+Th17.0 cells varied based on clinical outcome. The T-bet+ percentage of RORγt+Th17.0 cells was higher in the cases (subject group with PFT changes) as compared to controls (stable group) (27 vs. 16%, p = 0.0040). In comparisons before and after subjects' PFT changes, the T-bet+ frequency of RORγt+Th17.0 cells increased or decreased in the opposite direction of the PFT change. The percentage of these T-bet+ cells was also higher in those with greater numbers of involved organs. Serum levels of interferon-γ-induced chemokines, CXCL9, CXCL10, and CXCL11, and whole blood gene expression of IFN-γ-related genes including GBP1, TAP1, and JAK2 were independently positively associated with the T-bet+ frequencies of RORγt+Th17.0 cells. Conclusions: These data suggest that expression of T-bet in Th17.0 cells could reflect the extent of granulomatous inflammation in sarcoidosis patients because they represent a transition state leading to the Th17.1 cell phenotype. These findings indicate that Th17 plasticity may be part of the disease paradigm.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/922531z9Test