Pitabut, Nada

Preferred name

Pitabut, Nada

Alternative Name

Pitabut, N.

Main Affiliation

Faculty of Medicine

nada.pi@kmitl.ac.th

Now showing 1 - 9 of 9

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Coordinated in vitro release of granulysin, perforin and IFN-γ in tb and HIV/TB co-infection associated with clinical outcomes before and after anti-TB treatment
(2020-08-01)
Pitabut, Nada
;
Dhepakson, Panadda
;
Sakurada, Shinsaku
;
Keicho, Naoto
;
Khusmith, Srisin
Granule-associated killing molecules released from cytotoxic T lymphocytes participate as a crucial step in immunity against tuberculosis (TB), but the role of coordinated production remains controversial. Coordinated release of effector molecules in vitro after stimulating peripheral blood mononuclear cells (PBMCs) of active TB or HIV/TB coinfection patients with PPD, purified protein derivative of tuberculin and avirulent Mtb, H37Ra, an attenuated strain were investigated in association with clinical outcomes. Perforin, granzyme-B, granulysin and IFN-γ were measured using ELISA. Before anti-TB treatment, PBMCs of TB stimulated with PPD or H37Ra released higher perforin, granzyme-B, and granulysin levels than in HIV/TB and released significantly higher IFN-γ (p = 0.045, p = 0.022). Granulysin positively correlated with perforin in TB (p = 0.042, r = 0.385), HIV/TB coinfection (p = 0.003, r = 0.941) after PPD stimulation, and after H37Ra stimulation in TB (p = 0.005, r = 0.549), but negatively correlated with granzyme B in TB (p = 0.042, r = −0.386), HIV/TB coinfection (p = 0.042, r = 0.754) were noted. After anti-TB treatment, increased levels of perforin, granulysin and IFN-γ in TB or HIV/TB upon PPD or H37Ra stimulation, and decreased granzyme-B levels after PPD (p = 0.003) or H37Ra (p = 0.028) stimulation in TB were observed. These results suggest that granulysin may act synergistic with perforin and IFN-γ in TB, indicating its crucial function in host immunity to tuberculosis. Future studies with larger numbers of patients ought to be conducted in the future.
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Cytokine and chemokine kinetics in natural human dengue infection as predictors of disease outcome
(2025-12-01)
Jiravejchakul, Natnicha
;
Chan-in, Wilawan
;
Thuncharoen, Walairat
;
Pakchotanon, Pattarakul
;
Duangchinda, Thaneeya
Dengue is an important tropical disease with considerable global impact. Despite this, there remains an urgent need for reliable biomarkers to predict disease severity, as well as effective antiviral drugs and targeted treatments. In this study, we conducted a comprehensive profiling of 41 plasma mediators in patients with asymptomatic dengue (AD) and symptomatic dengue (SD), which includes mild dengue fever (DF) and severe dengue hemorrhagic fever (DHF). Our findings revealed that the levels of nearly all measured mediators were consistently lower in AD compared to SD patients, suggesting a potential protective cytokine response signature. Time-course cytokine analysis in SD shown significantly elevated levels of pro-inflammatory cytokines and chemokines associated with inflammation and viral clearance upon the acute phase, while various growth factors were elevated during the convalescence. Notably, we identified elevated IL-15 levels in DHF patients three days before fever subsidence, highlighting its potential as an early prognostic biomarker for severe disease outcomes. Furthermore, prolonged high levels of IL-8 and IP-10 in DHF during the critical period may contribute to dengue immunopathogenesis. This study advances the understanding of cytokine dynamics in the natural course of human dengue infection, providing valuable insights for the development of targeted treatments and prognostic biomarkers.
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Distinct systemic immune responses in asymptomatic and symptomatic dengue virus infection
(2025-12-17)
Sungnak, Waradon
;
Jiravejchakul, Natnicha
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Poonpanichakul, Tiraput
;
Trakoolsoontorn, Chawinya
;
Srikor, Sirawit
A comprehensive understanding of human systemic immune responses to mosquito-borne dengue virus (DENV) infection is vital for addressing challenges posed by viral heterologous serotypes and potential adverse memory immune responses. Asymptomatic DENV infection offers an opportunity to explore protective immunity because infected individuals effectively clear the virus without symptomatic manifestations. However, data on asymptomatic dengue are scarce because of limited sample availability during silent viremia. Here, we conducted single-cell RNA and immune receptor sequencing of peripheral blood mononuclear cells (PBMCs) from donors with varying disease severities including asymptomatic dengue and performed longitudinal analysis in a symptomatic dengue cohort, enabling identification of distinct immune responses. In asymptomatic dengue, we observed potential indications of enhanced viral antigen processing via MHC-I, correlating with increased CD8 effector T cell activities, distinct NK cell profiles, and enriched IGHA1<sup>+</sup> plasmablasts. In contrast, symptomatic dengue cases exhibited indications toward antibody-mediated viral entry, elevated type I interferon responses, and IL-10–associated expansion of IGHG1<sup>+</sup> plasmablasts with biased V(D)J gene usage and a shared B cell receptor clonotype network. Our study reports a gene expression and immune receptor repertoire resource for systemic immune responses to DENV infection and suggests distinct mechanisms for potential protection and pathogenicity in individuals with asymptomatic compared with symptomatic dengue.
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Dengue viremia kinetics in asymptomatic and symptomatic infection
(2020-12-01)
Matangkasombut, Ponpan
;
Manopwisedjaroen, Kajohnpong
;
Pitabut, Nada
;
Thaloengsok, Sasikanya
;
Suraamornkul, Swangjit
Background: Dengue infection is a global health threat. While symptomatic cases contribute to morbidity and mortality, the majority of infected people are asymptomatic but serve as an important reservoir. However, the kinetics of viremia in asymptomatic infections remains unknown. Methods: We enrolled 279 hospital-based symptomatic index cases and quantified dengue virus (DENV) RNA at enrollment and at the day of defervescence. To identify asymptomatic cases, 175 household members of index cases were monitored for clinical symptoms during follow-up, and blood was taken twice weekly to test for and quantify DENV RNA until cleared. Results: We detected DENV in thirteen asymptomatic household members (7.43%). Their DENV serotypes were primarily the same as those of their family index cases. The median peak DENV viremia in asymptomatic subjects was lower than that of symptomatic individuals during the febrile phase, and the viral decay rate was slower in asymptomatic infections. Conclusions: DENV level and kinetics in asymptomatic individuals differed significantly from those of symptomatic cases. Despite the lower viremia, the slower decay rate in asymptomatic infections could lead to their prolonging the infectious reservoir. The improvement of transmission control to prevent such long-lived asymptomatic infections from transmitting the DENV is needed.
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VARIATIONS IN ANTIBODY RESPONSE TO PLASMODIUM VIVAX DUFFY BINDING PROTEIN REGION II OF INFECTED INDIVIDUALS IN THAILAND
(2022-09-01)
Tongshoob, Jarinee
;
Gosi, Panita
;
Pitabut, Nada
Duffy binding protein region II of Plasmodium vivax (PvDBPII) is a key target for vaccine-mediated immunity despite its highly polymorphic nature. Genetic diversity of PvDBPII within and between P. vivax isolates vary according to geographic regions, which might affect host immune response. This study evaluated DBPII allelic variations and naturally acquired immunity in P. vivax-infected individuals from malaria endemic areas of Thailand. Twenty-three 15-mer DBP peptides (DBPps) covering a critical binding motif in PvDBPII of P. vivax Thai isolates were evaluated for their immunogenicity in P. vivax-infected individuals (n = 82) compared to healthy non-parasite exposed controls (n = 39). Eighty-seven percent P. vivax-infected individuals had significantly higher anti-PvDBPII total IgG against six DBPps compared to controls. Anti-PvDBPII IgG1 was the most prominent subclass. Low IgG3 levels against Thai P. vivax-specific DBPp4 and DBPp5 and non-polymorphic DBPp22 were also detected. High IgG1 and low IgG3 response to DBPp4 and DBPp5 were associated with DBPp4 L333F (CTT>TTT) and DBPp5 S351C (AGT>TGT) mutations, in which the point mutation was C/A>T, whereas T/C>A/C mutation was present in other DBPps. These preliminary data revealed variations in levels of anti-PvDBPII IgG subclasses in P. vivax-infected individuals, which might impact vaccine development strategies against vivax malaria.
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Single-cell RNA sequencing reveals the expansion of circulating tissue-homing B cell subsets in secondary acute dengue viral infection
(2024-05-30)
Arora, Jantarika Kumar
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Matangkasombut, Ponpan
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Charoensawan, Varodom
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Opasawatchai, Anunya
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Sakuntabhai, Anavaj
The roles of antibodies secreted by subsets of B cells in dengue virus (DENV) infection have been extensively studied, yet, the contribution of tissue-homing B cells to antiviral immunity remains unclear. In this study, we performed a comprehensive analysis of B cell subpopulations in peripheral blood samples from DENV-infected patients using single-cell RNA-sequencing (scRNA-seq) datasets and flow cytometry. We showed that plasma cells (PCs) and plasmablasts (PBs) were the predominant B cell populations during the acute phase of secondary natural DENV infection, but not in convalescent phase nor in healthy controls. Interestingly, these cells expressed proliferation, adhesion, and tissue-homing genes, including SELPLG, a homing marker of the skin, the initial infected site of DENV. Flow cytometry analysis confirmed a significant upregulation of cell surface expression of a cutaneous lymphocyte-associated antigen (CLA) encoded by SELPLG in PCs and PBs, compared to naive and memory B cells from the same patients. The analysis of an independent single-cell B-cell receptor sequencing (scBCR-seq) dataset of DENV-infected patients revealed that the peripheral blood PCs and PBs exhibited the highest clonal expansion in secondary DENV infection compared to other B cell subsets. These clonally expanded cells also expressed the highest levels of tissue-homing genes, including SELPLG. In addition, by utilizing a public scRNA-seq dataset of SARS-CoV2 infection, we demonstrated the upregulation of several tissue-homing genes in PCs and PBs. Our study provides evidence for the potential roles of tissue-homing B cell subsets in the context of immune responses against viral infections in humans.
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Anti-DENV IgE correlates with dengue severity and triggers FcεRI-dependent basophil activation inhibited by Omalizumab
(2026-12-01)
Chan-in, Wilawan
;
Vacharathit, Vimvara
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Tancharoen, Walairat
;
Duangchinda, Thaneeya
;
Mongkolsapaya, Juthathip
Severe dengue, marked by plasma leakage, is often linked to secondary heterotypic dengue virus (DENV) infection. While mast cells and basophils contribute to dengue pathogenesis, the role of anti-DENV IgE remains unclear. Here, we investigated whether anti-DENV IgE promotes FcεRI-dependent basophil activation, potentially contributing to disease severity. Plasma from dengue fever (DF, n = 42) and dengue hemorrhagic fever (DHF, n = 56) patients, collected at febrile, defervescence, and convalescent phases, were analyzed using an in-house IgE-capture ELISA developed to detect antibodies against all four DENV serotypes. Functional assays employed RS-ATL8, a human FcεRI-expressing basophil reporter cell line, to assess IgE-mediated activation following DENV antigen cross-linking. The anti-IgE monoclonal antibody Omalizumab was used to evaluate FcεRI dependence. Anti-DENV IgE was detected in both DF and DHF, peaking at defervescence and significantly higher in DHF. Total IgE was elevated but did not differ between groups. About one-third of anti-DENV-IgE-positive plasma samples induced RS-ATL8 activation upon DENV challenge, an effect abolished by omalizumab. These findings indicate a potential pathogenic role of anti-DENV IgE and provide a rationale for further investigation of IgE-targeted interventions.
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Heterogeneity and dynamics of DENV-specific CD8 + T cells in dengue infection
(2026-12-01)
Srikor, Sirawit
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Sungnak, Waradon
;
Trakoolsoontorn, Chawinya
;
Poonpanichakul, Tiraput
;
Jiravejchakul, Natnicha
Dengue virus (DENV) is a major global health threat, with secondary heterotypic infections potentially inducing detrimental memory immune responses. Antigen-specific CD8 + T cells contribute to both protection and pathogenicity, yet how their phenotypic heterogeneity relates to disease severity remains unclear. Here, we performed plate-based single-cell RNA sequencing of circulating DENV-specific CD8 + T cells identified by HLA tetramers loaded with DENV NS3-derived epitopes. Using tetramer binding to peptides corresponding to the currently and serologically inferred dominant previously infecting serotypes, we identify distinct CD8 + T cell subsets associated with disease severity. Asymptomatic dengue is enriched for lower tetramer binding cells with moderate cytotoxic programs, whereas dengue hemorrhagic fever is associated with high tetramer binding CX3CR1 + CD8 + T cells exhibiting enhanced expression of genes related to T cell receptor signaling and cytotoxicity. T cell receptor repertoires are similar among symptomatic cases but displayed temporal dynamics. Overall, DENV NS3-specific CD8 + T cells across disease severity and time are associated with distinct transcriptomic states and T cell receptor features.
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Association between circulating cortisol and ACTH and severity of dengue infection in adult patients
(2019-01-01)
Sura-Amornkul, S.
;
Pitabut, N.
;
Pholtawornkulchai, K.
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Matangkasombut, P.
;
Sakuntabhai, A.
Objective: To study the kinetics of endocrine changes in adult patients with dengue hemorrhagic fever (DHF) and dengue fever (DF) and association to disease severity. Materials and Methods: This hospital-based observational clinical study involved 48 adult patients, 32 with DHF and 16 with DF, who presented with clinical features and positive serological testing for dengue infection on the day of diagnosis (D1). Serial circulating ACTH and cortisol concentrations were determined on D1, day of defervescence (Ddef), day 1 of convalescence (DC1 or 24 h after Ddef), day 2 of convalescence (DC2 or 48 h after Ddef), at 2-week follow-up (F1), and 2-month follow-up (F2). Results: The median cortisol concentration in the DHF group was higher on D1 than that at F2. This was not found in patients with DF who had no difference of median cortisol concentration at D1 and F2. The median ACTH concentrations in both DHF and DF groups were low on D1 and trended toward recovery at F2. There was association between circulating ACTH and cortisol concentrations at D1 in patients with the severity of DHF (r = 0.309, p = 0.042) but not of DF. Conclusion: The ACTH and cortisol responses were associated with severity of dengue infection and recovery after 2 months.

Pitabut, Nada

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