Association between blood inflammatory status and the survival of tuberculosis: a five-year cohort study DOI Creative Commons
Yating Ji,

Qingyao Xie,

Wei Wei

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

Background Blood inflammatory status is closely associated with tuberculosis (TB) progression. Emerging indices from different leukocyte subtypes have become a prognostic hotspot for various diseases, yet their application in TB prognosis remains limited. This study aims to assess the impact of on patients’ and its potential as indicator optimize assessment therapeutic strategies. Methods included 4027 patients admitted tuberculosis-designated hospital Shenzhen January 2017 December 2022. Patients were classified into three statuses (Q1-Q3) based each index’s level. We conducted Cox regression restricted cubic splines (RCS) analyses evaluate association between unfavorable outcome, subgroup understand heterogeneous associations among subpopulations, receiver operating characteristic (ROC) performance treatment outcomes. Results During 48991.79 person-months follow-up involving patients, 225 outcomes occurred. Multivariable indicated that Q3 levels CAR, CLR, dNLR, NLR, SII, SIRI increased risk outcome by 45%-99% (HR: 1.45-1.99, all P <0.050), whereas ENR reduced 29% 0.71, =0.040) compared Q1. RCS curves revealed linear positive SIRI, negative (all nonlinear>0.050), nonlinear MLR, PNI nonlinear<0.050). Subgroup identified across age, sex, BMI, comorbidities, drug resistance interaction<0.050), attenuated effects SII aged 30-60 years, male, BMI≥24.0 kg/m², smokers, retreatment cases, those tumor. ROC analysis demonstrated stable predictive performances (AUC: 0.785–0.804 at 6-month, 0.781–0.793 9-month, 0.762–0.773 12-month), combination significantly optimized basic model (9-month AUC: 0.811 vs 0.780, =0.024; 12-month 0.794 0.758, =0.013). Conclusion Pretreatment blood effectively predicts patients. Our findings hold significant clinical value patient management warrant prospective evaluation future studies.

Язык: Английский

Human memory CD4+ T cells recognize Mycobacterium tuberculosis-infected macrophages amid broader pathogen-specific responses DOI Creative Commons

V. Stetsenko,

Daniel P. Gail,

Scott M. Reba

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 27, 2025

Recognition of macrophages infected with Mycobacterium tuberculosis (Mtb) is essential for CD4 + T cells to prevent (TB). Yet not all antigen-specific recognize in human and murine models. Using monocyte-derived (MDMs) autologous memory from individuals latent Mtb infection (LTBI), we quantify cell activation response macrophages. antigen receptor (TCR) sequencing revealed >70% unique >90% total Mtb-specific TCR clonotypes stable LTBI are linked recognition macrophages, while a subset required exogenous exposure, suggesting incomplete recognition. Clonotypes specific multiple antigens other pathogens were identified, indicating non-specific activation. Single-cell transcriptomics demonstrates express signature effector functions dominated by IFNγ, TNF, IL-2, GM-CSF or chemokine production signaling. We propose TB vaccines that elicit capable recognizing expressing these canonical will offer protection against TB.

Язык: Английский

Процитировано

0
MDSC depletion during immunization with heat-killed Mycobacterium tuberculosis increases protection against BCG infection. DOI Creative Commons

Arpa Aintablian,

Haisam Alattar,

Laura Cyran

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Фев. 5, 2025

Abstract Tuberculosis (TB) is still one of the deadliest infectious diseases globally. Although i.d. BCG immunization offers limited protection, a vaccine based on Mycobacterium tuberculosis (Mtb) has yet to be approved. Our previous findings demonstrated that s.c. with heat-killed Mtb significantly increased number monocytic myeloid-derived suppressor cells (M-MDSC) in mice. Therefore, we hypothesized defense against subsequent infection would impaired Mtb-immunized Surprisingly, mice vaccinated were protected and showed elevated frequencies activation DC mycobacteria-specific T despite high activity M-MDSC. Genetic ablation CCR2 + or pharmacological intervention all-trans retinoic acid (ATRA) reduced frequency Mtb-induced M-MDSC, enhanced frequencies, dendritic (DC) CD4 cells, resulted decreased bacterial loads lung spleen. These offer fresh perspectives TB vaccination using parallel unwanted vaccine-induced M-MDSC depletion by ATRA further tips balance towards immunity should considered an adjunct host-directed therapy vaccines humans.

Язык: Английский

Процитировано

0
Seasonal variation in Swedish sarcoidosis patients with severe hypercalcemia DOI Creative Commons
Joanna Werner, Pernilla Darlington, Natalia V. Rivera

и другие.

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Фев. 13, 2025

Abstract Sarcoidosis associated hypercalcemia (SAHC) is a challenging clinical problem as it can result in severe morbidity. Sunlight exposure and conversion of vitamin D to its active form by macrophages granulomas have been suggested possible causes. We aimed disentangle mechanisms behind SAHC investigating any associations with season, granuloma burden lung macrophages. Patients were identified from local cohort. The patients divided two groups: mild SAHC. Data on when occurred, HLA-DRB1 alleles, bronchoalveolar lavage fluid (BALF) macrophages, extrapulmonary manifestations (EPM) serum angiotensin-converting enzyme (s-ACE) marker for retrieved medical records. Out 83 SAHC, was found 36 patients, 75% whom presented between May October ( p < 0.001). No seasonal variation observed hypercalcemia. Elevated s-ACE more common (84% patients), compared 46% the group *04 frequent hypercalcemia, (67% vs. 32%, 0.01). Results support being sun exposure. Risk factors be observant are elevated *04.

Язык: Английский

Процитировано

0
Association between blood inflammatory status and the survival of tuberculosis: a five-year cohort study DOI Creative Commons
Yating Ji,

Qingyao Xie,

Wei Wei

и другие.

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Март 21, 2025

Background Blood inflammatory status is closely associated with tuberculosis (TB) progression. Emerging indices from different leukocyte subtypes have become a prognostic hotspot for various diseases, yet their application in TB prognosis remains limited. This study aims to assess the impact of on patients’ and its potential as indicator optimize assessment therapeutic strategies. Methods included 4027 patients admitted tuberculosis-designated hospital Shenzhen January 2017 December 2022. Patients were classified into three statuses (Q1-Q3) based each index’s level. We conducted Cox regression restricted cubic splines (RCS) analyses evaluate association between unfavorable outcome, subgroup understand heterogeneous associations among subpopulations, receiver operating characteristic (ROC) performance treatment outcomes. Results During 48991.79 person-months follow-up involving patients, 225 outcomes occurred. Multivariable indicated that Q3 levels CAR, CLR, dNLR, NLR, SII, SIRI increased risk outcome by 45%-99% (HR: 1.45-1.99, all P &lt;0.050), whereas ENR reduced 29% 0.71, =0.040) compared Q1. RCS curves revealed linear positive SIRI, negative (all nonlinear&gt;0.050), nonlinear MLR, PNI nonlinear&lt;0.050). Subgroup identified across age, sex, BMI, comorbidities, drug resistance interaction&lt;0.050), attenuated effects SII aged 30-60 years, male, BMI≥24.0 kg/m², smokers, retreatment cases, those tumor. ROC analysis demonstrated stable predictive performances (AUC: 0.785–0.804 at 6-month, 0.781–0.793 9-month, 0.762–0.773 12-month), combination significantly optimized basic model (9-month AUC: 0.811 vs 0.780, =0.024; 12-month 0.794 0.758, =0.013). Conclusion Pretreatment blood effectively predicts patients. Our findings hold significant clinical value patient management warrant prospective evaluation future studies.

Язык: Английский

Процитировано

0