Immune mediators as plasma biomarkers for identifying household contacts and classifying clinical forms and leprosy reactionsCarvalho, Pascoal-Xavier, Araújo
et alFront Immunol (2025) 16, 1513060
Abstract: The present study aimed to evaluate the performance of plasma immune mediators in classifying leprosy patients [L(PB) and L(MB), paucibacillary and multibacillary leprosy, respectively], leprosy reaction patients (T1LR and T2LR, type 1 and type 2 leprosy reaction, respectively), household contacts (HHC), and non-infected (NI) controls. Quantitative measurements of these immune mediators were carried out using high-throughput multiplex microbead array. The results demonstrated that most of the plasma immune mediators were increased in all clinical groups compared with NI controls. Higher frequencies but lower maximum magnitudes of increase (fold change according to NI) were observed for T1LR (63%, 6.1×) and T2LR (63%, 9.7×) compared with HHC (48%, 68.5×), L(PB) (56%, 8.5×), and L(MB) (48%, 37.9×). The bi-dimensional scattering profiles (magnitude order vs. significance) identified a higher number of immune mediators in T2LR (12/27) compared with HHC (8/27), L(PB) (7/27), L(MB) (5/27), and T1LR (5/27). CXCL8 was selected as the parameter with the highest accuracy and significance [area under the receiver operating characteristic curve (AUC) = 0.98, p = 0.0002] in classifying NI vs. HHC. CCL3 (C-C motif chemokine ligand 3) was the single analyte with moderate accuracy and significance (AUC = 0.74, p = 0.0422) in classifying L(PB) vs. L(MB). IL-9 was selected as an attribute with moderate accuracy and significance (AUC = 0.77, p = 0.0041) in classifying T1LR vs. T2LR. Decision tree algorithms confirmed the high accuracy (96%) of CXCL8 in classifying NI vs. HHC. The use of CCL3 followed by IFN-γ classified L(MB) vs. L(PB) with high accuracy (93%). Moreover, the analysis of IL-9 followed by IL-6 and CXCL10 classified T1RL vs. T2RL with high accuracy (96%). In general, combined stepwise algorithms showed enhanced classification accuracy compared with single-attribute analysis. Together, our findings supported the potential use of plasma immune mediators as complementary laboratory biomarkers for the identification of HHC and the classification of distinct clinical forms of leprosy and leprosy reactions.Copyright © 2025 Carvalho, Pascoal-Xavier, Araújo, Martins, Teixeira-Carvalho, Gomes, Amaral, Peruhype-Magalhães, Coelho-dos-Reis, Martins-Filho and Araújo.
An interleukin-9-ZBTB18 axis promotes germinal center development of memory B cellsLuo, Hou, Wang
et alImmunity (2025)
Abstract: Memory B cell (MBC) development from germinal centers (GCs) entails profound changes in cell cycling, localization, and survival. Here, we examined the mechanisms that induce the memory program, focusing on interleukin (IL)-9, given its importance for normal recall antibody responses. Using adoptive transfer and radiation chimera models, we found that T cell-derived IL-9 was required for MBC development and function. By contrast, B cells deficient in IL-9 generated functionally normal MBCs that support antibody recall normally. IL-9 induced expression of the transcriptional repressor ZBTB18 in GC memory precursor cells and MBCs. ZBTB18 was dispensable for naive B cell activation and GC formation but required for the development of GC-derived MBCs. ZBTB18 directly repressed the expression of a suite of genes encoding cyclin and cyclin-dependent kinases, pro-apoptotic genes Bid and Casp3, and the GC-retaining factor S1pr2. Lack of IL-9-mediated instruction or intrinsic programming by ZBTB18 impaired GC-derived MBC development and antibody recall. Thus, an IL-9-ZBTB18 axis instructs the development of functional B cell memory from GCs.Copyright © 2025 The Authors. Published by Elsevier Inc. All rights reserved.
Gut commensals-derived succinate impels colonic inflammation in ulcerative colitisDalal, Sadhu, Batra
et alNPJ Biofilms Microbiomes (2025) 11 (1), 44
Abstract: Gut microbiota-derived metabolites play a crucial role in modulating the inflammatory response in inflammatory bowel disease (IBD). In this study, we identify gut microbiota-derived succinate as a driver of inflammation in ulcerative colitis (UC) by activating succinate-responsive, colitogenic helper T (Th) cells that secrete interleukin (IL)-9. We demonstrate that colitis is associated with an increase in succinate-producing gut bacteria and decrease in succinate-metabolizing gut bacteria. Similarly, UC patients exhibit elevated levels of succinate-producing gut bacteria and luminal succinate. Intestinal colonization by succinate-producing gut bacteria or increased succinate availability, exacerbates colonic inflammation by activating colitogenic Th9 cells. In contrast, intestinal colonization by succinate-metabolizing gut bacteria, blocking succinate receptor signaling with an antagonist, or neutralizing IL-9 with an anti-IL-9 antibody alleviates inflammation by reducing colitogenic Th9 cells. Our findings underscore the role of gut microbiota-derived succinate in driving colitogenic Th9 cells and suggesting its potential as a therapeutic target for treating IBD.© 2025. The Author(s).
[Clinical and immunological relationships in patients with early schizophrenia]Serazetdinova, Petrova, Dorofeykov
et alZh Nevrol Psikhiatr Im S S Korsakova (2025) 125 (2), 35-42
Abstract: To study clinical and immunological relationships in patients with early schizophrenia during remission.Forty-eight patients (53% females and 47% males) were examined at the initial stage of schizophrenia during remission (age 28.3±5.8 years). The duration of the disease was 2.7±1.3 years. The control group consisted of healthy males and females aged 18 to 30 years. The study used clinical-psychopathological and laboratory methods, as well as scale assessment.In patients with early schizophrenia in remission, in 70% of cases, there was an increase in blood levels of cytokines IL-6, IL-9, IL-10, IL-13, IL-22, TNF-α, CCL20/MIP3α (p<0.001) compared to the control group. Levels of IL-4 (r=0.45; p=0.023) and IL-9 (r=0.48; p=0.014) correlated with disease duration. The PANSS composite index correlated with IL-6 levels (r=0.46; p=0.022). Levels of several pro-inflammatory blood cytokines were significantly higher in patients treated with first-generation antipsychotics compared with patients treated with second-generation antipsychotics (p<0.001).Changes in the concentrations of pro-inflammatory and anti-inflammatory interleukins, which are involved in the development of a nonspecific immune response as part of the systemic inflammatory response in patients with early schizophrenia during remission, have been demonstrated. The results suggest that in patients with the first episode of schizophrenia, the activation of immune inflammation plays a significant role in the development of the disease. Over time, such activation may stabilize and is associated with a greater severity of psychopathological symptoms.
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