Sepsis in patients with liver cirrhosis is associated with poor outcomes. Early prognostic stratification is crucial for guiding clinical decisions. We investigated the relationship between serum chloride levels and mortality in septic patients with liver cirrhosis. Septic patients with liver cirrhosis were obtained from the Medical Information Mart for Intensive Care (MIMIC-IV 3.0) database. We used multivariable Cox regression models and restricted cubic spline analysis to assess the association with serum chloride levels and 30-day, 60-day and 365-day all-cause mortality. 2778 septic patients with liver cirrhosis were included and 827 (29.77

Background:Patients with rheumatic diseases are at high risk for latent tuberculosis infection (LTBI) reactivation. We aimed to evaluate whether a modified 3-month regimen (3HP-PUMCH) was non-inferior to the standard 9-month isoniazid regimen (9H) for tuberculosis preventive treatment in this vulnerable population. Methods:We conducted a multicenter, open-label, randomized, non-inferiority trial at nine tertiary general hospitals in China. Eligible participants were adults (18-70 years) with high-risk rheumatic diseases and LTBI undergoing immunosuppressive therapy. Patients were randomized (1:1) to receive either the 3HP-PUMCH regimen (twice-weekly rifapentine 450 mg plus daily isoniazid 300 mg) or the 9H regimen (daily isoniazid 300 mg). The primary endpoint was the occurrence of tuberculosis, with a non-inferiority margin of 1.4 percentage points. Analysis used the modified intention-to-treat population. The trial was registered with Chinese Clinical Trial Registry ChiCTR1800018242. Findings:Between 19 September 2018 and 18 August 2021, 536 patients with rheumatic diseases were enrolled. The cumulative rate of tuberculosis was 0.00% (0 of 249, 95% CI 0.00-1.47) in the 3HP-PUMCH group, compared with 1.15% (3 of 260, 95% CI 0.24-3.34) in the 9H group, with a rate difference of -1.15 percentage points (95% CI -2.4 to 0.14). Drug discontinuation rates due to serious adverse events or tuberculosis occurrence were 2.8% (7 of 249) in the 3HP-PUMCH group and 1.9% (5 of 260) in the 9H group (p = 0.509). Adverse drug reactions occurred in 24 (9.6%) of 249 patients versus 39 (15.0%) of 260 (p = 0.066), with hepatotoxicity in 11 (4.4%) of 249 versus 27 (10.4%) of 260 (p = 0.010). 223 (89.6%) of 249 patients completed treatment in the 3HP-PUMCH and 237 (91.2%) of 260 in the 9H group (p = 0.54). Interpretation:The short-course 3HP-PUMCH regimen was non-inferior to the 9H regimen in preventing tuberculosis and demonstrated a favorable safety profile, with high treatment completion in LTBI patients with rheumatic diseases. This regimen might be more suitable for patients with underlying diseases and those on concomitant medications. Funding:National Natural Science Foundation of China.

CD8+ T cell exhaustion contributes to viral persistence in patients with hepatitis B virus (HBV) infection. Emerging evidence identifies CXCR5+CD8+ T cells as a distinct subset with dual antiviral and B-cell helper functions across disease contexts. Peripheral blood mononuclear cells from chronic HBV-infected patients were used to characterize the frequency, phenotype and functions of CXCR5+CD8+ T cells using flow cytometry. A publicly available single-cell RNA sequencing (scRNA-seq) dataset was used to elucidate transcriptional profiles. Chronic hepatitis B (CHB) patients exhibited expanded CXCR5+CD8+ T cells that inversely correlated with hepatitis B surface antigen (HBsAg) and HBV DNA levels (P < 0.05). Despite elevated inhibitory receptors, these cells maintained enhanced IL-2 production, preserved IFN-γ, TNF-α and perforin output, and reduced granzyme B compared with CXCR5- counterparts. Meanwhile, CXCR5+ subsets express costimulatory molecules and secrete higher levels of IL-21 to promote B-cell responses. scRNA-seq analysis confirmed these effector-helper features. HBV-specific CXCR5+CD8+ T cells secrete more IFN-γ and TNF-α relative to CXCR5- subsets. Furthermore, PD-1 expressing CXCR5+CD8+ T cells expressed higher memory related molecule and produced more effector cytokines. In conclusion, CXCR5+CD8+ T cells play a potential role in viremia control in CHB patients via both direct antiviral effector function and the modulation of humoral immunity. PD-1 in these cells seems not to show exhaustion characteristics. Thus, strategies that booster CXCR5+CD8+ T cell responses may help control HBV infection.

Active tuberculosis (ATB) largely relied on clinical diagnosis because of the limited sensitivity of microbiologic testing. We assessed whether complete blood cell count (CBC)-derived ratios could assist in ATB diagnosis and risk assessment. This study enrolled 305 people with ATB and 171 healthy controls (HC) to evaluate the diagnostic efficiency of CBC-derived ratios for ATB by receiver operating characteristic curves and validated in a multi-center rheumatic disease (RD) cohort, in which a nested case-control study was designed to reveal the relationship between CBC-derived ratios and risk of developing ATB. Platelet, monocyte, and neutrophil count increased, but lymphocyte count decreased, thereby, platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and neutrophil-to-lymphocyte ratio (NLR) were elevated significantly in people with ATB compared to HC, the similar tendency was shown between people with post- and pre-the onset ATB. These indices were restored after anti-tuberculosis treatment. Moreover, PLR, MLR, NLR, especially combining monocyte count, PLR, and NLR (area under the curve (AUC) = 0.916, P < 0.001) exhibited good diagnostic efficiency for ATB. Additionally, people with RD concomitant ATB demonstrated a similar tendency of CBC-derived ratios but their diagnostic efficiency for ATB was limited in the RD population. Interestingly, the risk of developing ATB of people with PLR ≥ 130.27 was higher by 23.761-fold than those with PLR < 130.27 in this population within one year. CBC-derived ratios have limited standalone diagnostic value in RD populations (AUC = 0.637) but may aid risk stratification. CBC-derived ratios should be considered complementary tools, not replacements, for microbiological tests, particularly in resource-limited settings or to prompt further definitive testing.

Background:Understanding the natural history of hepatitis B virus (HBV) infection helps determine the optimal timing of antiviral therapy. However, a gap exists in the literature regarding the dynamics of the natural history of HBV infection in pregnant women with chronic hepatitis B (CHB). This study aimed to explore the natural history of HBV infection during pregnancy and the postpartum period. Methods:We conducted a retrospective-prospective real-world study involving 276 pregnant women with CHB. Infection dynamics during pregnancy were characterized in 228 hepatitis B e-antigen (HBeAg)-positive and 48 HBeAg-negative participants, respectively, and during postpartum follow-up in 108 HBeAg-positive and 21 HBeAg-negative participants. HBeAg-positive participants received short-term antiviral intervention according to current guidelines. Liver disease progression was also evaluated. Results:Throughout pregnancy, the proportion of patients in the immune tolerance (IT) phase increased progressively, whereas the proportions of patients in the HBeAg-positive indeterminate phase (IP) and HBeAg-positive immune-active (IA) phase decreased. In the third trimester, the IT phase was dominant (48.7%), followed by the HBeAg-positive IP phase (24.6%), the HBeAg-positive IA phase (9.4%), the inactive carrier (IC) phase (9.4%), the HBeAg-negative IP phase (7.1%), and the HBeAg-negative IA phase (0.9%). During the postpartum period, a numerically higher cumulative incidence of phase maintenance (p = 0.150) and a significantly lower cumulative incidence of transition to the HBeAg-positive IA phase (p < 0.001) were observed in pregnant women in the IT phase compared with those in the HBeAg-negative IP phase. The cumulative incidence of phase maintenance (p = 0.900) and transition to the HBeAg-negative IA phase (p = 0.560) were comparable between pregnant women in the IC phase and those in the HBeAg-negative IP phase. The risk of postpartum liver disease progression was low among pregnant women across all disease phases. Conclusion:Pregnancy may have a pronounced impact on the dynamics of HBV infection in HBeAg-positive patients, particularly those in the IP phase at 24-28 weeks of gestation. Close postpartum monitoring is therefore warranted for this specific population. Clinical trial registration:https://www.clinicaltrials.gov, identifier ChiCTR2100054116.

BACKGROUND & AIMS:Current guidelines for antiviral treatment of chronic hepatitis B are based on age, alanine aminotransferase levels, viral load, a family history of hepatitis B virus-related cirrhosis, or hepatocellular carcinoma, while not considering sex as a factor. METHODS:This retrospective longitudinal cohort study included 1543 untreated patients with chronic hepatitis B (760 male and 774 female) not meeting antiviral treatment criteria in previous guidelines and investigated sex differences in liver disease progression according to the latest Chinese guidelines for the prevention and treatment of chronic hepatitis B (2022). RESULTS:The cumulative incidence of cirrhosis was significantly higher in male patients compared with female patients among all untreated patients with chronic hepatitis B (23.1% vs 7.9%; P < .001), treatment-eligible patients (25.3% vs 8.0%; P = .001), and treatment-ineligible patients (20.6% vs 7.3%; P < .001). Male sex was strongest risk factor for cirrhosis (hazard ratio, 2.474; 95% confidence interval, 1.628-3.760; P < .001) among untreated patients with chronic hepatitis B. Male patients showed a relatively high incidence of cirrhosis, although not meeting antiviral treatment criteria, whereas female patients showed a relatively low incidence of cirrhosis, although meeting antiviral treatment criteria. In treatment-eligible female patients, those with abnormal alanine aminotransaminase (10.4%) showed a numerically higher incidence of cirrhosis compared with those with normal alanine aminotransaminase. In treatment-ineligible patients, male sex was a risk factor for cirrhosis. CONCLUSIONS:In conclusion, male patients showed a higher risk of cirrhosis than female patients in untreated patients with chronic hepatitis B. Expanding antiviral treatment criteria may be considered in male patients, but not in female patients. Initiating antiviral treatment may be stratified by sex.

Patients with rheumatic diseases (RDs) have a high risk of latent tuberculosis infection (LTBI) reactivation. However, research on tuberculosis preventive treatment (TPT) in this specific patient group remains limited. Additionally, the safety of the WHO - recommended 3 - month regimen of weekly rifapentine (RFT) plus isoniazid (INH) (3HP) has raised concerns among the Chinese population. This study aims to evaluate the efficacy, safety, and treatment completion of a modified 3HP regimen to a 9 - month INH monotherapy regimen in this vulnerable population.Flowchart of study participant intervention and follow-up. We conducted a multicenter, open-label, randomized noninferiority trial comparing a modified 3-month regimens of twice weekly RFT at 450mg plus daily INH at a maximum dose of 300mg (3HP-PUMCH) versus 9-month daily isoniazid at a maximum dose of 300mg (9H) in patients with RDs. Subjects were enrolled from 9 tertiary hospitals across China and followed for 2 years. The primary endpoint was confirmed active TB (ATB), with a noninferiority margin of 1.4%. A total of 536 patients with RDs were enrolled. In the modified intention-to-treat analysis, no cases of ATB occurred among 249 RDs patients in the 3HP-PUMCH group, with a cumulative rate of 0.00% (95% confidence interval [CI] 0.00 - 1.47), while 3 cases were observed among 260 patients in the 9H group, with a cumulative rate of 1.15% (95% CI 0.24 - 3.34), and the rate difference was -1.15% (95% CI -2.4 - 0.14). Rates of drug discontinuation due to serious adverse events or the occurrence of ATB in the 3HP-PUMCH group and the 9H group were 2.8% and 1.9% respectively (p=0.509), rates of investigator-assessed preventive drugs-related adverse reactions were 9.6% and 15.0% respectively (p = 0.066), with the rates of hepatotoxicity related to preventive drugs were 4.4% and 10.4% respectively (p = 0.010). Treatment completion rates were 89.6% in the 3HP-PUMCH group and 91.2% in the 9H group (p=0.542). The 3HP-PUMCH was as effective as the 9H in preventing ATB and demonstrated a favorable safety profile and high completion in LTBI patients with high-risk RDs. Moreover, this novel TPT regimen might be more suitable for patients with underlying diseases and those on concomitant medications, potentially offering a more practical and manageable option in complex clinical scenarios. All Authors: No reported disclosures

Systemic vasculitis patients are at a higher risk of developing latent tuberculosis infection (LTBI). However, there is currently no literature elucidating the positivity rate and risk factors for LTBI in systemic vasculitis patients. Our study is a multi-center, cross-sectional study that enrolled systemic vasculitis patients from 13 comprehensive hospitals in China. T-SPOT.TB as the screening method for LTBI, the study investigated the positivity rate of LTBI in systemic vasculitis patients and the factors associated with T-SPOT.TB results. A total of 191 systemic vasculitis patients were included and the positive rate of T-SPOT.TB was 31.4

Background:Patients with rheumatic disease (RD) are particularly vulnerable to progressing to tuberculosis disease (TBD). The effectiveness of tuberculosis preventive treatment (TPT) in this high risk group needs systematic assessment. Methods:We conducted a systematic review and meta-analysis by searching PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and China National Knowledge Internet (CNKI) for relevant cohort studies from inception through January 2025. Eligible studies evaluated the incidence of TBD and/or the effectiveness of TPT in patients with RD. Two authors independently reviewed and extracted summary data from published reports. Pooled incidence rate (IR), risk ratio (RR) and their 95% confidence interval (CI) were calculated as the primary effect measure. Prospero registration number is CRD42023473966. Findings:64 studies with 116,015 patients with RD were included to evaluate effectiveness of TPT. TPT decreased the overall risk of TBD in patients with RD (RR: 0.76, 95% CI 0.63-0.91). TPT showed better effectiveness in high tuberculosis (TB) burden countries/regions (RR: 0.46, 95% CI 0.27-0.77). Using isoniazid (INH) monotherapy for 9-12 months was effective (RR: 0.54, 95% CI 0.35-0.85). Taking tuberculin skin test (TST) combined with interferon gamma release assays (IGRA) as tuberculosis infection (TBI) screening methods might maximize the benefits of TPT (RR: 0.58, 95% CI 0.39-0.88). TPT showed optimal protective effects in patients with RD in TBI positive status (RR: 0.11, 95% CI 0.04-0.32). Compared with patients with RD receiving biologics, TPT showed better effects in patients with RD only receiving traditional treatment (RR: 0.44, 95% CI 0.27-0.73). And TPT performed more effectively in systematic lupus erythematosus (SLE) than arthritis. Interpretation:TPT decreased the risk of TBD in patients with RD, especially in TB high burden countries/regions. When using isoniazid monotherapy, extending the treatment course might have better protection. TST combined with IGRA might be optimal when screening the TBI. More types of RDs, short-course regimens containing rifamycins and high-quality randomized controlled trials (RCT) should be the focus of future research. Funding:This study was supported by the National Natural Science Foundation of China (82373648), Capital's Funds for Health Improvement and Research (2024-2-4016), and the National High Level Hospital Clinical Research Funding (2022-PUMCH-C-013, 2022-PUMCH-A-119).

Mother-to-child transmission (MTCT) is one of the main routes of transmission of HBV, and previous studies focused on the efficacy and safety of nucleoside analogues (NAs) in preventing MTCT. There are limited data on virologic changes of chronic hepatitis B (CHB) patients after discontinuing treatment postpartum and the efficacy of retreatment. A retrospective-prospective real-world pilot cohort study on pregnant women with CHB was conducted. Biochemical and virological characteristics (HBsAg, HBeAg and HBV DNA) in patients received NAs treatment pre-pregnancy (n = 24), patients discontinued treatment after delivery (n = 88) and retreatment patients (n = 22) were collected during follow-up. The incidences of HBeAg clearance, half decrease of HBsAg, 0.5 lg decrease of HBsAg and HBsAg < 1000 IU/mL in patients discontinuing treatment postpartum were 5.7

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health challenge, affecting millions annually and leading to substantial mortality, particularly in developing countries. The pathogen’s ability to persist latently and evade host immunity, combined with the emergence of drug-resistant strains, underscores the need for innovative therapeutic strategies. This review highlights the crucial role of interleukin-12 (IL-12) in coordinating immune responses against TB, focusing on its potential as an immunotherapy target. IL-12, a key Th1 cytokine, enhances cellular immunity by promoting Th1 cell differentiation and IFN-γ production, vital for Mtb clearance. By stimulating cytotoxic T lymphocytes and establishing immune memory, IL-12 supports robust host defense mechanisms. However, the complexity of IL-12 biology, including its roles in pro-inflammatory and regulatory pathways, necessitates a nuanced understanding for effective therapeutic use. Recent studies have shown how IL-12 impacts T cell synapse formation, exosome-mediated bystander activation, and interactions with other cytokines in shaping T cell memory. Genetic defects in the IL-12/IFN-γ axis link to susceptibility to mycobacterial diseases, highlighting its importance in TB immunity. The review also addresses challenges like cytokine imbalances seen in TNF-α/IFN-γ synergy, which exacerbate inflammation, and the implications for IL-12-based interventions. Research into modulating IL-12, including its use as an adjuvant and in recombinant vaccines, promises improved TB treatment outcomes and vaccine efficacy. The review concludes by stressing the need for continued investigation into IL-12’s molecular mechanisms towards precision immunotherapies to combat TB and its complications.

BACKGROUND AND OBJECTIVES:Patients with rheumatic immune diseases (RD) are considered a high-risk population for developing active tuberculosis (ATB). Timely and accurate diagnosis of ATB in RD patients is critical for optimizing treatment outcomes and improving prognosis. Both interferon-gamma release assays (IGRA) and the tuberculin skin test (TST) are immunological methods employed in the diagnosis of tuberculosis. However, the diagnostic accuracy of these tests in RD patients, who often experience immune dysfunction, remains underexplored. This study aims to compare the diagnostic accuracy of TST and T-SPOT.TB in RD patients with suspected tuberculosis symptoms. METHODS:This prospective study included RD patients presenting with any of the following symptoms-fever, cough, night sweats, or unexplained weight loss (all symptoms recommended by the World Health Organization for tuberculosis screening)-from September 2014 to September 2015. Both T-SPOT.TB and TST were performed, and patients were categorized into ATB and non-ATB groups based on clinical diagnosis (including microbiologically confirmed and clinically diagnosed cases). Receiver operating characteristic (ROC) curves were constructed to compare the diagnostic accuracy of T-SPOT.TB and TST for ATB and to determine the optimal cutoff values. Sensitivity, specificity, predictive values, and likelihood ratios were calculated, along with 95% confidence intervals (CIs). The concordance between T-SPOT.TB and TST in diagnosing ATB was also evaluated. RESULTS:A total of 300 RD patients were enrolled in the study. Of these, 35 (11.7%) were diagnosed with ATB, 258 (86.0%) were excluded from ATB, and 7 (2.3%) had an unclear diagnosis. Among the RD patients, the ATB group exhibited significantly higher frequencies of night sweats (34.3% vs. 14.0%, p=0.002) and unexplained weight loss (17.1% vs. 3.1%, p<0.001) compared to the non-ATB group, while no significant differences were observed between the groups for fever and cough. The area under the ROC curve (AUROC) for T-SPOT.TB was 0.89 (95% CI 0.82-0.95), while the AUROC for TST was 0.74 (95% CI 0.63-0.84), with T-SPOT.TB demonstrating significantly superior diagnostic accuracy (AUROC difference 0.15, 95% CI 0.06-0.24, p=0.001) (Figure). The optimal cutoff for T-SPOT.TB in diagnosing ATB was 24 spot-forming cells (SFCs) per 10^6 peripheral blood mononuclear cells (PBMCs), with sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, positive predictive value, and negative predictive value of 88.6%, 84.9%, 5.86, 0.13, 44.3%, and 98.2%, respectively. The optimal cutoff for TST was a 5mm induration diameter, yielding diagnostic metrics of 57.1%, 88.8%, 5.08, 0.48, 40.8%, and 93.9%, respectively. The sensitivity of T-SPOT.TB was significantly higher than that of TST (p=0.003), while no significant difference in specificity was observed (p=0.193). As the T-SPOT.TB spot count and TST induration diameter increased, the likelihood ratios for diagnosing ATB also increased. The agreement between T-SPOT.TB and TST in diagnosing ATB in RD patients was moderate (kappa=0.466, p<0.001), and parallel testing with TST did not improve the sensitivity of T-SPOT.TB. CONCLUSION:In RD patients with suspected ATB symptoms, both T-SPOT.TB and TST offer valuable diagnostic assistance. T-SPOT.TB demonstrates superior diagnostic accuracy, particularly in terms of sensitivity. Higher spot counts on T-SPOT.TB or larger induration diameters on TST should raise clinical suspicion for the presence of concurrent ATB.

Abstract Background Current immunological methods cannot accurately distinguish active tuberculosis (ATB) and latent tuberculosis infection (LTBI). The combination of latency-associated antigens with virulence antigens of Mtb enhances the discriminatory diagnostic ability. This study aims to screen and integrate dominant peptide segments of virulence factors and latency-associated antigens, verify their immunogenicity. Methods ATB patients and LTBI healthy healthcare workers were enrolled, and PBMCs were isolated. Peptide pools of ESAT-6, CFP-10, Rv1733c and Rv2028c were used as stimuli. The frequencies of total IFN-γ secretion, total IL-2 secretion, and dual secretion of IFN-γ and IL-2 were measured using the FluoroSpot assay. Dominant peptide segments for library construction were screened based on the cytokine secretion characteristics of ATB and LTBI. Clinical T-SPOT.TB-positive patients were included for the verification of the immunogenicity of the newly combined peptide library. Results Significant differences were found in the frequencies of specific T cells secreting IFN-γ, secreting IL-2, and dual-secreting IFN-γ and IL-2 between the ATB group and the LTBI group (p< 0.05) after stimulation with peptide pools from ESAT-6 and CFP-10, integrating six dominant peptide pools into the virulence antigen dominant peptide library. Similarly, six peptide pools from Rv1733c and Rv2028c were integrated into another dominant peptide library. The newly constructed library showed no significant differences (p >0.05) in the frequencies of total IFN-γ secretion, total IL-2 secretion, and dual secretion of IFN-γ and IL-2 compared to ESAT-6 combined with CFP-10, and the correlation coefficients were 0.947, 0.763, and 0.993, respectively. Similarly, the newly constructed latency-associated antigen library also showed no significant differences (p >0.05) in the frequencies of total IFN-γ secretion, total IL-2 secretion, and dual secretion of IFN-γ and IL-2 compared to Rv1733c combined with Rv2028c, and the correlation coefficients were 0.674, 0.562, and 0.692, respectively. Conclusion The newly constructed librarys retain good immunogenicity and can be further used clinically to evaluate the accuracy of ATB and LTBI differential diagnosis. Disclosures All Authors: No reported disclosures

Hepatitis B virus (HBV) infection is a global health concern. The current sequential endpoints for the treatment of HBV infection include viral suppression, hepatitis B e antigen (HBeAg) seroconversion, functional cure, and covalently closed circular DNA (cccDNA) clearance. Serum hepatitis B core-related antigen (HBcrAg) is an emerging HBV marker comprising three components: HBeAg, hepatitis B core antigen, and p22cr. It responds well to the transcriptional activity of cccDNA in the patient's liver and is a promising alternative marker for serological testing. There is a strong correlation, and a decrease in its level corresponds to sustained viral suppression. In patients with chronic hepatitis B (CHB), serum HBcrAg levels are good predictors of HBeAg seroconversion (both spontaneous and after antiviral therapy), particularly in HBeAg-positive patients. Both low baseline HBcrAg levels and decreasing levels early in antiviral therapy favored HBsAg seroconversion, which may serve as a good surrogate option for treatment endpoints. In this review, we summarize the role of serum HBcrAg in the treatment of CHB. Therefore, long-term continuous monitoring of serum HBcrAg levels contributes to the clinical management of patients with CHB and optimizes the choice of treatment regimen, making it a promising marker for monitoring HBV cure.

ObjectiveThis study aims to evaluate the diagnostic accuracy of a Mycobacterium tuberculosis (MTB)-specific triple-color FluoroSpot assay (IFN-γ/IL-2/TNF-α) in the differentiation of tuberculosis (TB) infection status in febrile patients.MethodFebrile patients with suspected active TB (ATB) were consecutively enrolled. The frequencies and proportions of MTB-specific T cells secreting IFN-γ, IL-2, and TNF-α were detected at the single-cell level by triple-color FluoroSpot assay. The diagnostic index was fitted with a binary logistic regression model, and the diagnostic accuracy was evaluated according to the receiver operating characteristic (ROC) curve. The sensitivity, specificity, predictive values (PV), and likelihood ratios (LR) were calculated.ResultA total of 210 febrile patients were enrolled, 53 patients were diagnosed with ATB (28 pathogen-confirmed vs. 25 clinically diagnosed) and 157 patients were non-ATB (84 with latent tuberculosis infection (LTBI) vs. 73 uninfected with MTB). Additionally, 30 pathogen-confirmed ATB patients were assembled. When diagnosing ATB, the area under the ROC curve (AUROC) of the MTB-specific triple-color FluoroSpot assay was significantly better than that of T-SPOT.TB (0.882 vs. 0.811, p = 0.017). With the fitted diagnostic index at a cutoff value of 0.378, the sensitivity, specificity, LR+, and LR- were 74.7%, 93.0%, 10.66, and 0.27, respectively. When differentiating ATB from LTBI, the AUROC of the FluoroSpot assay and T-SPOT.TB was 0.878 and 0.692, respectively (p < 0.001). With a diagnostic index of 0.413, the sensitivity, specificity, LR+, and LR were 77.1%, 85.7%, 5.40, and 0.27, respectively.ConclusionThe MTB-specific triple-color FluoroSpot (IFN-γ/IL-2/TNF-α) might be helpful for the differentiation of TB infection status in febrile patients.

Abstract Background Systemic Lupus Erythematosus (SLE), an autoimmune disease, involves multiple immune dysfunctions. The progression of M.tb infection is closely related to the host's immune status. Abnormal immune functions increase the risk of active tuberculosis (ATB), particularly in patients with autoimmune diseases. Meanwhile, both SLE and ATB’s clinical symptoms includes several overlaps, resulting in a diagnosis challenge when without etiological evidence. Forest plot showing the results of univariate logistic regression in the discovery cohort Methods We included 66 SLE patients with ATB hospitalized at Peking Union Medical College Hospital from 1975 to 2017, and 132 age matched SLE patients without ATB as the discovery cohort. An external validation cohort was drawn from the ETHERTB cohort, which covers rheumatic and immune disease patients from 13 tertiary hospitals in China. Univariate Logistic regression analysis was used in the discovery cohort to identify risk factors for ATB among SLE patients. A neural network algorithm was used to construct the clinical diagnostic model. The external validation cohort was used to validate the diagnostic potential of our model. models developed Importance of all risk factors (A) and variables included in our model (B). Neural network-based model architecture (C). Results In the discovery cohort, fever (OR=47.2), night sweats (OR=5.3), cough (OR=14.5), weight loss (OR=70.1), moderate to severe SLE disease activity (SLEDAI-2000 5-9, OR=5.1; SLEDAI-2000≥10, OR=6.7), close contact with TB (OR=7.8), T-SPOT.TB (OR=1.004), and the use of specific immunosuppressants such as azathioprine (AZA) (OR=3.4), leflunomide (LEF) (OR=2.7), cyclosporine A (CYSA) (OR=3.8), and a maximum daily dose of 30 mg of corticosteroids (OR=14.9) were identified as risk factors for ATB in SLE patients. Variables including fever, night sweats, cough, weight loss, TB contact, T-SPOT.TB, SLEDAI-2000, and maximum daily corticosteroids dose were included in the diagnostic model based on an importance threshold of 0.5. The model's AUC was 0.96(95%Cl: 0.927-0.996), with a sensitivity of 85.3%, specificity of 96.0%, and an accuracy of 93.7%. In the external validation cohort, the AUC was 0.88(95Cl: 0.800-0.963), sensitivity 84.4%, specificity 88.1%, and accuracy 88.0%. Evaluation of diagnosis model Distribution of risk scores in the discovery cohort (A) and validation cohort (B), and ROC curves in the discovery (C) and validation cohorts (D). Conclusion Our study constructed and validated a diagnostic model for ATB in SLE patients. The model demonstrated good diagnostic potential, which could assist in diagnosis in the absence of etiological evidence. Disclosures All Authors: No reported disclosures

OBJECTIVE:To explore Cytomegalovirus (CMV) antigen-specific multi-cytokine immune responses in patients with rheumatic disease (RD) under different CMV infection status. METHODS:A total of 60 RD patients in our center from March 2023 to August 2023 were enrolled. The patients were divided into latent CMV infection and active CMV infection, the latter was classified as subclinical CMV infection or CMV disease based on presence or absence of symptoms related to CMV. Whole blood was collected and stimulated with QuantiFERON-CMV antigen. The levels of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10, IL-17 and CXCL-2 in supernatant were measured by Luminex Assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different CMV infection status. RESULTS:The proportion of patients with severe lymphopenia was lowest in the latent CMV infection group, while there were no significant differences in medication usage in different CMV infection status. After stimulation with QF-CMV antigens, the levels of IFN-γ, TNF-α and IL-2 in the CMV disease group were significantly lower than those in the latent CMV infection group. CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia together provided the best discriminatory performance for distinguishing between latent and either active CMV infection patients (AUC = 0.854) or CMV disease patients (AUC = 0.935). CONCLUSION:Noninvasive peripheral blood biomarkers (the combination of CMV antigen-specific IFN-γ, TNF-α levels and severe lymphopenia) may have the potential to diferentiate different status of CMV infection in RD population.

Background More efficient and convenient diagnostic method is a desperate need to reduce the burden of tuberculosis (TB). This study explores the multiple cytokines secretion based on QuantiFERON-TB Gold Plus (QFT-Plus), and screens for optimal cytokines with diagnostic potential to differentiate TB infection status. Methods Twenty active tuberculosis (ATB) patients, fifteen patients with latent TB infection (LTBI), ten patients with previous TB and ten healthy controls (HC) were enrolled. Whole blood samples were collected and stimulated by QFT-Plus TB1 and TB2 antigens. The levels of IFN-γ, TNF-α, IL-2, IL-6, IL-5, IL-10, IP-10, IL-1Ra, CXCL-1 and MCP-1 in supernatant were measured by Luminex bead-based multiplex assays. The receiver operating characteristic curve was used to evaluate the diagnostic accuracy of cytokine for distinguishing different TB infection status. Results After stimulation with QFT-Plus TB1 and TB2 antigens, the levels of all cytokines, except IL-5 in TB2 tube, in ATB group were significantly higher than that in HC group. The levels of IL-1Ra concurrently showed the equally highest AUC for distinguishing TB infection from HC, followed by the levels of IP-10 in both TB1 tube and TB2 tube. Moreover, IP-10 levels displayed the largest AUC for distinguishing ATB patients from non-ATB patients. Meanwhile, the levels of IP-10 also demonstrated the largest AUC in both TB1 tube and TB2 tube for distinguishing ATB patients from LTBI. Conclusions In addition to conventional detection of IFN-γ, measuring IP-10 and IL-1Ra based on QFT-Plus may have the more tremendous potential to discriminate different TB infection status.