Transcatheter Aortic Valve Replacement in Low-Risk Patients at Four or More Years.

INTRODUCTION: Transcatheter aortic valve replacement (TAVR) is accepted as an alternative to surgical aortic valve replacement (SAVR) in patients with severe symptomatic aortic valve stenosis (AS). Prior studies have shown TAVR has comparable or superior outcomes to SAVR in intermediate and high-risk patients. However, there is paucity of data about outcome of TAVR versus SAVR in low surgical risk patients evaluated at 4 or more years post-procedure. METHODS: A systematic review of all published randomized controlled trials comparing TAVR and SAVR in patients at low-risk patients was completed. A random-effects model meta-analysis was performed to study major outcomes including all-cause mortality, stroke, myocardial infarction, and aortic valve re-intervention. RESULTS: 3 randomized trials comprising 2,644 patients (1,371 TAVR and 1,273 SAVR) with mean age of 74.3 ± 5.8 were included in this analysis. There was no significant difference in all-cause and cardiovascular mortality, stroke, myocardial infarction, and aortic valve reintervention between TAVR and SAVR groups at long-term follow up. TAVR was associated with higher rate of pacemaker implantation, while SAVR was associated with more atrial fibrillation. CONCLUSIONS: At 4 or more years of follow-up, TAVR is safe and has comparable outcomes to SAVR in patients with low surgical risk. Possibility of TAVR and its risks and benefits should be discussed with patients with low surgical risk.

Transcatheter aortic valve replacement achieves similar predicted effective orifice area to surgical aortic valve replacement in bicuspid aortic stenosis.

BACKGROUND: Studies comparing transcatheter and surgical aortic valve replacement (TAVR and SAVR) for patients with trileaflet aortic stenosis (AS) have found similar or larger effective orifice area (EOA) for TAVR prostheses. To our knowledge, no studies have compared EOA in patients undergoing TAVR versus SAVR for bicuspid AS. METHODS: We retrospectively compared prosthetic valvular sizing and predicted EOA for patients with bicuspid AS undergoing TAVR or SAVR at our institution between January 1, 2016, and December 31, 2021. We excluded patients undergoing procedures for indications other than AS and those without a pre-procedural gated Chest CT. Comparisons included demographics, comorbidities, annular size, prosthetic valve size, predicted EOA and prosthesis-patient mismatch (PPM) for TAVR (N = 78) and SAVR (N = 74) cohorts. RESULTS: TAVR patients had smaller pre-procedural annular area (501.7 mm2 vs. 571.8 mm2, p < 0.05) and annular perimeter (80.6 mm vs. 86.5 mm, p < 0.05), but larger mean implanted prosthetic valve size (26.4 mm vs 24.2 mm, p < 0.001) compared to SAVR patients. No differences were observed in predicted EOA, predicted EOA indexed to patient body surface area (EOAi), or predicted PPM grade between TAVR and SAVR groups, including in cohorts sorted by pre-procedural annular size. CONCLUSIONS: For bicuspid AS patients undergoing aortic valve replacement, TAVR achieves similar predicted EOA to SAVR. These data support the use of TAVR in selected patients with bicuspid AS and can inform heart team discussions.

Platelet TLR7 is essential for the formation of platelet-neutrophil complexes and low-density neutrophils in lupus nephritis.

OBJECTIVES: Platelets and low-density neutrophils (LDNs) are major players in the immunopathogenesis of SLE. Despite evidence showing the importance of platelet-neutrophil complexes (PNCs) in inflammation, little is known about the relationship between LDNs and platelets in SLE. We sought to characterize the role of LDNs and Toll-like receptor 7 (TLR7) in clinical disease. METHODS: Flow cytometry was used to immunophenotype LDNs from SLE patients and controls. The association of LDNs with organ damage was investigated in a cohort of 290 SLE patients. TLR7 mRNA expression was assessed in LDNs and high-density neutrophils (HDNs) using publicly available mRNA sequencing datasets and our own cohort using RT-PCR. The role of TLR7 in platelet binding was evaluated in platelet-HDN mixing studies using TLR7-deficient mice and Klinefelter syndrome patients. RESULTS: SLE patients with active disease have more LDNs, which are heterogeneous and more immature in patients with evidence of kidney dysfunction. LDNs are platelet bound, in contrast to HDNs. LDNs settle in the peripheral blood mononuclear cell (PBMC) layer due to the increased buoyancy and neutrophil degranulation from platelet binding. Mixing studies demonstrated that this PNC formation was dependent on platelet-TLR7 and that the association results in increased NETosis. The neutrophil:platelet ratio is a useful clinical correlate for LDNs, and a higher NPR is associated with past and current flares of LN. CONCLUSIONS: LDNs sediment in the upper PBMC fraction due to PNC formation, which is dependent on the expression of TLR7 in platelets. Collectively, our results reveal a novel TLR7-dependent crosstalk between platelets and neutrophils that may be an important therapeutic opportunity for LN.

Heart failure with preserved ejection fraction risk is associated with prevalence and severity of obstructive sleep apnea.

STUDY OBJECTIVES: While heart failure with preserved ejection fraction (HFpEF) is associated with the presence of obstructive sleep apnea (OSA), few studies have examined the association between scoring systems used to predict HFpEF risk, such as the H2FPEF and HFA-PEFF scores, and OSA prevalence and severity. METHODS: We performed chart review on all patients who underwent both an echocardiogram and sleep study at the University of Pennsylvania between July 1, 2020, and June 30, 2022. There were 277 patients in the final cohort after excluding patients with relevant comorbidities. Associations between echocardiographic parameters and OSA severity, as well as between H2FPEF score and OSA severity, were examined using linear tests of trend. The association between H2FPEF score and prevalent OSA was examined with logistic regression. RESULTS: OSA severity was associated with echocardiographic markers, including left atrial volume index (P = .03) and left ventricular relative thickness (P = .008). Patients with high H2FPEF risk scores had over 17-fold higher odds of prevalent OSA compared with those with low-risk scores (17.7; 95% CI 4.3, 120.7; P < .001). Higher H2FPEF scores were strongly correlated with OSA severity (P < .001). After controlling for body mass index, H2FPEF scores were not associated with prevalence or severity of OSA. CONCLUSIONS: In an ambulatory population referred for sleep study and echocardiogram, markers of diastolic dysfunction were associated with OSA severity. OSA prevalence and severity were associated with increased H2FPEF scores, although these associations were largely explained by obesity. Clinicians should have low thresholds for referring patients with OSA for cardiac workup and patients with HFpEF for sleep study. CITATION: Connolly JE, Genuardi MV, Mora JI, Prenner SB. Heart failure with preserved ejection fraction risk is associated with prevalence and severity of obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):381-387.

A novel GPI-anchored dominant-negative TGF-ß receptor II renders T cells unresponsive to TGF-ß signaling.

Transforming growth factor ß (TGF-ß) is a pleiotropic cytokine expressed by a wide range of cell types and is known for hampering the effectiveness of cancer immune cell therapeutic approaches. We have designed a novel construct containing the extracellular domain of the TGF-ß receptor II linked to a glycosylphosphatidylinositol (GPI) anchor (GPI-ecto-TßRII) lacking the transmembrane and cytoplasmic signaling domain of TGF-ß receptor II (TßRII). T cells transduced with lentivirus expressing the GPI-ecto-TßRII construct show 5 to 15 times higher membrane expression compared with a previously established dominant-negative receptor carrying a truncated signaling domain. GPI-ecto-TßRII expression renders T cells unresponsive to TGF-ß-induced signaling seen by a lack of SMAD phosphorylation upon exogeneous TGF-ß treatment. Transduced T cells continue to express high levels of IFNγ and granulocyte-macrophage colony-stimulating factor (GM-CSF), among other cytokines, in the presence of TGF-ß while cytokine expression in untransduced T cells is being markedly suppressed. Furthermore, T cells expressing GPI-ecto-TßRII constructs have been shown to efficiently capture and inactivate TGF-ß from their environment. These results indicate the potential benefits of GPI-ecto-TßRII expressing cytotoxic T cells (CTLs) in future cell therapies.

Themis controls T cell activation, effector functions, and metabolism of peripheral CD8+ T cells.

Themis is important in regulating positive selection of thymocytes during T cell development, but its role in peripheral T cells is less understood. Here, we investigated T cell activation and its sequelae using a tamoxifen-mediated, acute Themis deletion mouse model. We find that proliferation, effector functions including anti-tumor killing, and up-regulation of energy metabolism are severely compromised. This study reveals the phenomenon of peripheral adaptation to loss of Themis, by demonstrating direct TCR-induced defects after acute deletion of Themis that were not evident in peripheral T cells chronically deprived of Themis in dLck-Cre deletion model. Peripheral adaptation to long-term loss was compared using chronic versus acute tamoxifen-mediated deletion and with the (chronic) dLck-Cre deletion model. We found that upon chronic tamoxifen-mediated Themis deletion, there was modulation in the gene expression profile for both TCR and cytokine signaling pathways. This profile overlapped with (chronic) dLck-Cre deletion model. Hence, we found that peripheral adaptation induced changes to both TCR and cytokine signaling modules. Our data highlight the importance of Themis in the activation of CD8+ T cells.

An Exploratory Study Investigating the Prevalence of Gastrointestinal Symptoms in Collegiate Division I American Football Athletes.

Gastrointestinal (GI) symptoms may limit performance, but their prevalence and impact among team sports athletes is not well-documented. The objective of this study was to examine the prevalence of GI symptoms in a small sample of collegiate DI American football athletes, using a survey including the Gastrointestinal Symptoms Ratings Scale (GSRS). Forty-six athletes responded to the survey and reported scores for the 15-question GSRS with additional questions about dietary habits and supplement use. A total of 44 athletes were included in the study (45% of the current roster, age: 20.7 ± 1.7 years, 50% Afro-American or black, 39% skill position, 18% NSAIDs use, and 41% reporting protein supplement use); approximately half of the athletes (52%) reported experiencing GI complaints during exercise. Two-thirds of the athletes (61%) reported at least one or more GI symptoms in general, and 50% reported at least four moderate complaints. Seven athletes (16%) reported ≥2 severe GI symptoms with 5-13 moderate complaints. The most reported symptom was stomach pain (39%, n = 17), followed by hunger pain (36%, n = 16). Athletes reporting the use of protein supplements reported a higher GSRS score (22.0 and interquartile range (IQR) 17.0-31.8) vs. athletes not reporting protein use (15.0 and IQR 15.0-19.3), p = 0.001. Most athletes surveyed reported experiencing GI symptoms. A small group of these athletes reported multiple, varied, and severe symptoms that were associated with self-reported protein supplement use. In conclusion, the number of complaints varied among athletes, confirming the value of integrating the GSRS for screening purposes, and the expected need for individual dietary treatment approaches.

Hospital Consolidation: The Rise of Geographically Distant Mergers.

This Viewpoint discusses how and why cross-market hospital mergers are different than prototypical within-market mergers in their effects on patients and communities, why the trend may be accelerating, and future policy and research directions.

A phase I study of an adenoviral vector delivering a MUC1/CD40-ligand fusion protein in patients with advanced adenocarcinoma.

Cancer vaccines as immunotherapy for solid tumours are currently in development with promising results. We report a phase 1 study of Ad-sig-hMUC1/ecdCD40L (NCT02140996), an adenoviral-vector vaccine encoding the tumour-associated antigen MUC1 linked to CD40 ligand, in patients with advanced adenocarcinoma. The primary objective of this study is safety and tolerability. We also study the immunome in vaccinated patients as a secondary outcome. This trial, while not designed to determine clinical efficacy, reports an exploratory endpoint of overall response rate. The study meets its pre-specified primary endpoint demonstrating safety and tolerability in a cohort of 21 patients with advanced adenocarcinomas (breast, lung and ovary). The maximal dose of the vaccine is 1 ×1011 viral particles, with no dose limiting toxicities. All drug related adverse events are of low grades, most commonly injection site reactions in 15 (71%) patients. Using exploratory high-dimensional analyses, we find both quantitative and relational changes in the cancer immunome after vaccination. Our data highlights the utility of high-dimensional analyses in understanding and predicting effective immunotherapy, underscoring the importance of immune competency in cancer prognosis.

First-in-Human Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Rapidly Developed SARS-CoV-2 Therapeutic Antibody, AOD01, in Healthy Adults.

INTRODUCTION: AOD01 is a novel, fully human immunoglobulin (Ig) G1 neutralizing monoclonal antibody that was developed as a therapeutic against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). This first-in-human study assessed safety, tolerability, pharmacokinetics (PK), and pharmacodynamics of AOD01 in healthy volunteers. METHODS: Intravenous doses of AOD01 were evaluated in escalating cohorts [four single-dose cohorts (2, 5, 10, and 20 mg/kg) and one two-dose cohort (two doses of 20 mg/kg, 24 h apart)]. RESULTS: Twenty-three subjects were randomized to receive AOD01 or a placebo in blinded fashion. A total of 34 treatment-emergent adverse events (TEAEs) were reported; all were mild in severity. Related events (headache and diarrhea) were reported in one subject each. No event of infusion reactions, serious adverse event (SAE), or discontinuation due to AE were reported. The changes in laboratory parameters, vital signs, and electrocardiograms were minimal. Dose-related exposure was seen from doses 2 to 20 mg/kg as confirmed by Cmax and AUC0-tlast. The median Tmax was 1.5-3 h. Clearance was dose independent. Study results revealed long half-lives (163-465 h). Antidrug antibodies (ADA) to AOD01 were not detected among subjects, except in one subject of the two-dose cohort on day 92. Sustained ex vivo neutralization of SARS-CoV-2 was recorded until day 29 with single doses from 2 to 20 mg/kg and until day 43 with two doses of 20 mg/kg. CONCLUSIONS: AOD01 was safe and well tolerated, demonstrated dose-related PK, non-immunogenic status, and sustained ex vivo neutralization of SARS-CoV-2 after single intravenous dose ranging from 2 to 20 mg/kg and two doses of 20 mg/kg and show good potential for treatment of SARS-CoV-2 infection. (Health Sciences Authority identifier number CTA2000119).

ZAKα-driven ribotoxic stress response activates the human NLRP1 inflammasome.

Human NLRP1 (NACHT, LRR, and PYD domain-containing protein 1) is an innate immune sensor predominantly expressed in the skin and airway epithelium. Here, we report that human NLRP1 senses the ultraviolet B (UVB)- and toxin-induced ribotoxic stress response (RSR). Biochemically, RSR leads to the direct hyperphosphorylation of a human-specific disordered linker region of NLRP1 (NLRP1DR) by MAP3K20/ZAKα kinase and its downstream effector, p38. Mutating a single ZAKα phosphorylation site in NLRP1DR abrogates UVB- and ribotoxin-driven pyroptosis in human keratinocytes. Moreover, fusing NLRP1DR to CARD8, which is insensitive to RSR by itself, creates a minimal inflammasome sensor for UVB and ribotoxins. These results provide insight into UVB sensing by human skin keratinocytes, identify several ribotoxins as NLRP1 agonists, and establish inflammasome-driven pyroptosis as an integral component of the RSR.

Population-centric risk prediction modeling for gestational diabetes mellitus: A machine learning approach.

AIMS: The heterogeneity in Gestational Diabetes Mellitus (GDM) risk factors among different populations impose challenges in developing a generic prediction model. This study evaluates the predictive ability of existing UK NICE guidelines for assessing GDM risk in Singaporean women, and used machine learning to develop a non-invasive predictive model. METHODS: Data from 909 pregnancies in Singapore's most deeply phenotyped mother-offspring cohort study, Growing Up in Singapore Towards healthy Outcomes (GUSTO), was used for predictive modeling. We used a CatBoost gradient boosting algorithm, and the Shapley feature attribution framework for model building and interpretation of GDM risk attributes. RESULTS: UK NICE guidelines showed poor predictability in Singaporean women [AUC:0.60 (95% CI 0.51, 0.70)]. The non-invasive predictive model comprising of 4 non-invasive factors: mean arterial blood pressure in first trimester, age, ethnicity and previous history of GDM, greatly outperformed [AUC:0.82 (95% CI 0.71, 0.93)] the UK NICE guidelines. CONCLUSIONS: The UK NICE guidelines may be insufficient to assess GDM risk in Asian women. Our non-invasive predictive model outperforms the current state-of-the-art machine learning models to predict GDM, is easily accessible and can be an effective approach to minimize the economic burden of universal testing & GDM associated healthcare in Asian populations.

Dendritic cell therapy with CD137L-DC-EBV-VAX in locally recurrent or metastatic nasopharyngeal carcinoma is safe and confers clinical benefit.

INTRODUCTION: Epstein-Barr virus (EBV) is associated with nasopharyngeal carcinoma (NPC), and provides a target for a dendritic cell (DC) vaccine. CD137 ligand (CD137L) expressed on antigen presenting cells, costimulates CD137-expressing T cells, and reverse CD137L signaling differentiates monocytes to CD137L-DC, a type of DC, which is more potent than classical DC in stimulating T cells. METHODS: In this phase I study, patients with locally recurrent or metastatic NPC were administered CD137L-DC pulsed with EBV antigens (CD137L-DC-EBV-VAX). RESULTS: Of the 12 patients treated, 9 received full 7 vaccine doses with a mean administered cell count of 23.9 × 106 per dose. Treatment was well tolerated with only 4 cases of grade 1 related adverse events. A partial response was obtained in 1 patient, and 4 patients are still benefitting from a progression free survival (PFS) of currently 2-3 years. The mean pre-treatment neutrophil: lymphocyte ratio was 3.4 and a value of less than 3 was associated with prolonged median PFS. Progressors were characterized by a high frequency of naïve T cells but a low frequency of CD8+ effector T cells while patients with a clinical benefit (CB) had a high frequency of memory T cells. Patients with CB had lower plasma EBV DNA levels, and a reduction after vaccination. CONCLUSION: CD137L-DC-EBV-VAX was well tolerated. The use of CD137L-DC-EBV-VAX is demonstrated to be safe. Consistent results were obtained from all 12 patients, indicating that CD137L-DC-EBV-VAX induces an anti-EBV and anti-NPC immune response, and warranting further studies in patients post effective chemotherapy. PRECIS: The first clinical testing of CD137L-DC, a new type of monocyte-derived DC, finds that CD137L-DC are safe, and that they can induce an immune response against Epstein-Barr virus-associated nasopharyngeal carcinoma that leads to tumor regression or prevents tumor progression.

Systemic inflammation, innate immunity and pathogenesis after Zika virus infection in cynomolgus macaques are modulated by strain-specificity within the Asian lineage.

Zika virus (ZIKV) is an emerging arbovirus with recent global expansion. Historically, ZIKV infections with Asian lineages have been associated with mild disease such as rash and fever. However, recent Asian sub-lineages have caused outbreaks in the South Pacific and Latin America with increased prevalence of neurological disorders in infants and adults. Asian sub-lineage differences may partially explain the range of disease severity observed. However, the effect of Asian sub-lineage differences on pathogenesis remains poorly characterized. Current study conducts a head-to-head comparison of three Asian sub-lineages that are representative of the circulating ancestral mild Asian strain (ZIKV-SG), the 2007 epidemic French Polynesian strain (ZIKV-FP), and the 2013 epidemic Brazil strain (ZIKV-Brazil) in adult Cynomolgus macaques. Animals infected intervenously or subcutaneously with either of the three clinical isolates showed sub-lineage-specific differences in viral pathogenesis, early innate immune responses and systemic inflammation. Despite the lack of neurological symptoms in infected animals, the epidemiologically neurotropic ZIKV sub-lineages (ZIKV-Brazil and/or ZIKV-FP) were associated with more sustained viral replication, higher systemic inflammation (i.e. higher levels of TNFα, MCP-1, IL15 and G-CSF) and greater percentage of CD14+ monocytes and dendritic cells in blood. Multidimensional analysis showed clustering of ZIKV-SG away from ZIKV-Brazil and ZIKV-FP, further confirming sub-lineage differences in the measured parameters. These findings highlight greater systemic inflammation and monocyte recruitment as possible risk factors of adult ZIKV disease observed during the 2007 FP and 2013 Brazil epidemics. Future studies should explore the use of anti-inflammatory therapeutics as early treatment to prevent ZIKV-associated disease in adults.

Effective Killing of Acute Myeloid Leukemia by TIM-3 Targeted Chimeric Antigen Receptor T Cells.

Acute myeloid leukemia (AML) is an aggressive disease with poor outcomes, overwhelmingly due to relapse. Minimal residual disease (MRD), defined as the persistence of leukemic cells after chemotherapy treatment, is thought to be the major cause of relapse. The origins of relapse in AML have been traced to rare therapy-resistant leukemic stem cells (LSCs) that are already present at diagnosis. Effective treatment strategies for long-term remission are lacking, as it has been difficult to eliminate LSCs with conventional therapy. Here, we proposed a new approach based on the chimeric antigen receptor (CAR)-directed T lymphocytes, targeting T-cell immunoglobulin, and mucin domain 3 (TIM-3) to treat MRD in patients with AML. TIM-3 is selected as the target because it is highly expressed on AML blasts and LSCs in most subtypes regardless of the patient's genetic characteristics and treatment course. Moreover, it is absent in the normal hematopoietic stem cells, granulocytes, naïve lymphocytes, and most normal nonhematopoietic tissues. Using a naïve human Fab phage display library, we isolated an anti-human TIM-3 antibody and designed a second-generation anti-TIM-3. Our anti-TIM-3 CAR T cells exhibit potent antileukemic activity against AML cell lines and primary AML blasts, and in the mouse models. More importantly, we demonstrate efficient killing of the primary LSCs directly isolated from the patients. Hence, eradication of the LSCs present in the MRD by anti-TIM-3 CAR T-cell therapy following the first-line treatment may improve the clinical outcomes of patients with AML.

Bayesian analysis of cytokines and chemokine identifies immune pathways of HBsAg loss during chronic hepatitis B treatment.

Our objective was to examine differences in cytokine/chemokine response in chronic hepatitis B(CHB) patients to understand the immune mechanism of HBsAg loss (functional cure) during antiviral therapy. We used an unbiased machine learning strategy to unravel the immune pathways in CHB nucleo(t)side analogue-treated patients who achieved HBsAg loss with peg-interferon-α(peg-IFN-α) add-on or switch treatment in a randomised clinical trial. Cytokines/chemokines from plasma were compared between those with/without HBsAg loss, at baseline, before and after HBsAg loss. Peg-IFN-α treatment resulted in higher levels of IL-27, IL-12p70, IL-18, IL-13, IL-4, IL-22 and GM-CSF prior to HBsAg loss. Probabilistic network analysis of cytokines, chemokines and soluble factors suggested a dynamic dendritic cell driven NK and T cell immune response associated with HBsAg loss. Bayesian network analysis showed a dominant myeloid-driven type 1 inflammatory response with a MIG and I-TAC central module contributing to HBsAg loss in the add-on arm. In the switch arm, HBsAg loss was associated with a T cell activation module exemplified by high levels of CD40L suggesting T cell activation. Our findings show that more than one immune pathway to HBsAg loss was found with peg-IFN-α therapy; by myeloid-driven Type 1 response in one instance, and T cell activation in the other.

Monocytic Myeloid-Derived Suppressor Cells Underpin Resistance to Adoptive T Cell Therapy in Nasopharyngeal Carcinoma.

Advanced, late-stage Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) is incurable, and its treatment remains a clinical and therapeutic challenge. Results from a phase II clinical trial in advanced NPC patients employing a combined chemotherapy and EBV-specific T cell (EBVST) immunotherapy regimen showed a response rate of 71.4%. Longitudinal analysis of patient samples showed that an increase in EBV DNA plasma concentrations and the peripheral monocyte-to-lymphocyte ratio negatively correlated with overall survival. These parameters were combined into a multivariate analysis to stratify patients according to risk of death. Immunophenotyping at serial time points showed that low-risk individuals displayed significantly decreased amounts of monocytic myeloid-derived suppressor cells postchemotherapy, which subsequently influenced successful cytotoxic T-lymphocyte (CTL) immunotherapy. Examination of the low-risk group, 2 weeks post-EBVST infusion, showed that individuals with a greater overall survival possessed an increased frequency of CD8 central and effector memory T cells, together with higher levels of plasma interferon (IFN)-γ, and cytotoxic lymphocyte-associated transcripts. These results highlight the importance of the rational selection of chemotherapeutic agents and consideration of their impact on both systemic immune responses and downstream cellular immunotherapy outcomes.

Singapore Ocular Tuberculosis Immunity Study (SPOTIS): Role of T-lymphocyte Profiling in Patients with Presumed Ocular Tuberculosis.

Objective: A prospective clinical study to assess the utility of CD4 + T cell lymphocyte profiling from peripheral blood in patients with ocular tuberculosis (TB).Methods: Thirty-six Asian patients with presumed diagnosis of ocular TB were recruited for T-lymphocyte profiling. MTB antigen specific CD4 assay was set up, and flow cytometric data were analyzed using FlowJo software.Results: There was no significant difference between treatment responders and non-responders for the proportion of CD4 + T cells specific for PPD or ESAT-6+ CFP-10, but treatment responders did have significantly higher frequency of CD38+ (p = .0357) and CD38+ HLA-DR+ (p = .0357) on the PPD-specific CD4 + T cells.Conclusion: This study is one of the first of its kind to look into MTB specific T cell activation marker profiling of peripheral blood in patients with ocular TB. Further studies need to be undertaken to assess the utility of CD4 + T cell phenotypes as a biomarker for ocular TB.