scholarly journals IDENTIFICATION OF CORRELATES OF PROTECTION FROM YERSINIA PESTIS ON A MOUSE MODEL AND ASSESSMENT OF THE POSSIBILITY OF USING THEM AS MARKERS OF VACCINATION EFFICIENCY IN HUMANS

2021 ◽  
Author(s):  
S. Klyueva ◽  
S. Bugorkova ◽  
T. Kashtanova
Keyword(s):  
Yersinia Pestis ◽  
Protective Efficacy ◽  
Control Group ◽  
Moderate Increase ◽  
Correlates Of Protection ◽  
Tnf Α ◽  
Ifn Γ ◽  
Commercial Kits ◽  
High Level ◽  
Plague Vaccine

In conditions when the assessment of changes in the incidence rate cannot be used as an indicator of the effectiveness of a live plague vaccine, there is a real need to search for other, in particular, immunological correlates of the vaccine's protection. Modern concepts of the patho- and immunogenesis of plague make it possible to narrow the search for possible correlates of protection, focusing on the assessment of cellular factors of the immune response. The aim of this work is to identify the immunological correlates of protection against plague in mice immunized with Yersinia pestis EV NIIEG, and to assess the dynamics of selected markers of immunological effectiveness of vaccination in people vaccinated against plague. Experimental model - BALB / c mice, 40 individuals in each group were immunized with Y. pestis EV at doses of 2 × 102, 1 × 103, 5 × 103, 2.5 × 104 CFU, and on the 21st day they were infected with Y. pestis 231 at a dose of 400 LD50. Control group - intact animals. Immunogenicity was determined by ImD50 and calculated by the Kerber method. Volunteers - 20 people who were first vaccinated with the live plague vaccine and 20 people who were not vaccinated against the plague (comparison group). The production of cytokines in the blood was determined on an enzyme-linked immunosorbent analyzer "LAZURIT" (Dynex Technologies, USA): in mice before infection with Y. pestis 231 on the 14th and 21st days after vaccination; in humans - before vaccination, 1, 6 and 12 months after vaccination. We used commercial kits in accordance with the instructions for their use. The immunized mice showed a significant increase (2.2 times) in the induced IFN-γ production and a moderate increase in the concentration of TNF-α, IL-10 and IL-17A on the 14th day of immunogenesis. A high correlation was found between the survival rate of animals and the level of antigen- / mitogen-induced production of IFN-γ (r = 0.94, p = 0.039), both on the 14th and 21st days, as well as a noticeable relationship with the level of production of IL-10 and IL-17A on the 14th day of immunogenesis. In volunteers one month after inoculation, an increase in the indicators of mitogen-induced production of all detectable cytokines was noted, but the levels of IFN-γ, TNF-α, IL-10, IL-17A significantly increased by the 6th month of observation (p <0.05), although only for IFN-γ and IL-17A, the induced production of these cytokines remained at a sufficiently high level up to a year after inoculation. Thus, IFN-γ and IL-17A can be considered as possible informative correlates of protection of mice from Y. pestis on days 14 and 21, considering the increase in the induced production of these cytokines as adequate markers of the protective efficacy of immunization, and the assessment of the dynamics of these parameters in volunteers vaccinated with the plague live vaccine, an increase in the levels of IFN-γ and IL-17A can be considered a favorable prognostic marker of the immunological efficacy of the vaccine in the period from the 6th to the 12th month of observation.

scholarly journals CCL19 enhances CD8+ T-cell responses and accelerates HBV clearance

2021 ◽  
Author(s):  
Yan Yan ◽  
Wei Zhao ◽  
Wei Liu ◽  
Yan Li ◽  
Xu Wang ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Crucial Role ◽  
Cell Activation ◽  
Hbv Infection ◽  
Host Immune System ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level

Abstract Background Chemokine (C–C motif) ligand 19 (CCL19) is a leukocyte chemoattractant that plays a crucial role in cell trafficking and leukocyte activation. Dysfunctional CD8+ T cells play a crucial role in persistent HBV infection. However, whether HBV can be cleared by CCL19-activated immunity remains unclear. Methods We assessed the effects of CCL19 on the activation of PBMCs in patients with HBV infection. We also examined how CCL19 influences HBV clearance and modulates HBV-responsive T cells in a mouse model of chronic hepatitis B (CHB). In addition, C–C chemokine-receptor type 7 (CCR7) knockdown mice were used to elucidate the underlying mechanism of CCL19/CCR7 axis-induced immune activation. Results From in vitro experiments, we found that CCL19 enhanced the frequencies of Ag-responsive IFN-γ+ CD8+ T cells from patients by approximately twofold, while CCR7 knockdown (LV-shCCR7) and LY294002 partially suppressed IFN-γ secretion. In mice, CCL19 overexpression led to rapid clearance of intrahepatic HBV likely through increased intrahepatic CD8+ T-cell proportion, decreased frequency of PD-1+ CD8+ T cells in blood and compromised suppression of hepatic APCs, with lymphocytes producing a significantly high level of Ag-responsive TNF-α and IFN-γ from CD8+ T cells. In both CCL19 over expressing and CCR7 knockdown (AAV-shCCR7) CHB mice, the frequency of CD8+ T-cell activation-induced cell death (AICD) increased, and a high level of Ag-responsive TNF-α and low levels of CD8+ regulatory T (Treg) cells were observed. Conclusions Findings in this study provide insights into how CCL19/CCR7 axis modulates the host immune system, which may promote the development of immunotherapeutic strategies for HBV treatment by overcoming T-cell tolerance.

scholarly journals High Levels of TNF-α and TIM-3 as a Biomarker of Immune Reconstitution Inflammatory Syndrome in People with HIV Infection

Life ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 527
Author(s):  
Lucero A. Ramon-Luing ◽  
Ranferi Ocaña-Guzman ◽  
Norma A. Téllez-Navarrete ◽  
Mario Preciado-García ◽  
Dámaris P. Romero-Rodríguez ◽  
...  
Keyword(s):  
Immune Reconstitution Inflammatory Syndrome ◽  
Immune Reconstitution ◽  
Control Group ◽  
Hiv Patients ◽  
Art Initiation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Α Level ◽  
Inflammatory Syndrome

Immune reconstitution inflammatory syndrome (IRIS) is an exacerbated immune response that can occur to HIV+ patients after initiating antiretroviral therapy (ART). IRIS pathogenesis is unclear, but dysfunctional and exhausted cells have been reported in IRIS patients, and the TIM-3/Gal-9 axis has been associated with chronic phases of viral infection. This study aimed to evaluate the soluble levels of TIM-3 and Gal-9 and their relationship with IRIS development. TIM-3, Gal-9, TNF-α, IFN-γ, IL-6, TNFR1, TNFR2, E-cadherin, ADAM10, and ADAM17 were measured to search for IRIS-associated biomarkers in plasma samples from 0-, 4-, 8-, 12-, and 24-weeks after ART initiation of 61 HIV+ patients (15 patients developed IRIS, and 46 did not). We found that patients who developed IRIS had higher levels of TIM-3 [median 4806, IQR: 3206–6182] at the time of the IRIS events, compared to any other follow-up time evaluated in these patients or compared with a control group of patients who did not develop IRIS. Similarly, IRIS patients had a higher TNF-α level [median 10.89, IQR: 8.36–12.34] at IRIS events than any other follow-up time evaluated. Other molecules related to the TIM-3 and TNF-α pathway (Gal-9, IL-6, IFN-γ, TNFR1, TNFR2, ADAM-10, and ADAM-17) did not change during the IRIS events. In conclusion, our data suggest that a high level of soluble TIM-3 and TNF-α could be used as an IRIS biomarker.

scholarly journals Heavy metal intoxication compromises the host cytokine response in Ascaris Suum model infection

2016 ◽  
Vol 53 (1) ◽  
pp. 14-23 ◽  
Author(s):  
E. Dvorožňáková ◽  
M. Dvorožňáková ◽  
J. Šoltys
Keyword(s):  
Heavy Metal ◽  
Immune Response ◽  
Ascaris Suum ◽  
Cytokine Response ◽  
Parasitic Infections ◽  
Tnf Α ◽  
Ifn Γ ◽  
High Level ◽  
Larval Burden ◽  
Heavy Metal Intoxication

SummaryLead (Pb), Cadmium (Cd) and Mercury (Hg) are recognized for their deleterious effect on the environment and immunity where subsequently compromised immune response affects the susceptibility to the potential parasitic infections. This study examined the host cytokine response after heavy metal intoxication (Pb, Cd, and Hg) and subsequent Ascaris suum infection in BALB/c mice. Pb modulated murine immune response towards the Th2 type of response (delineated by IL-5 and IL-10 cytokine production) what was also dominant for the outcome of A. suum infection. Chronic intoxication with Pb caused a more intensive development of the parasite infection. Cd stimulated the Th1 immune response what was associated with increase in IFN-γ production and reduction of larvae present in the liver of intoxicated mice. The larval burden was also low in mice intoxicated with Hg. This was probably not related to the biased Th1/Th2 type of immune response, but rather to the bad host conditions caused by mercury toxicity and high level of pro-cachectic cytokine TNF-α.

scholarly journals Cytokine expression in the duodenal mucosa of patients with visceral leishmaniasis

2010 ◽  
Vol 43 (4) ◽  
pp. 393-395 ◽  
Author(s):  
Kleber Giovanni Luz ◽  
Felipe Francisco Tuon ◽  
Maria Irma Seixas Duarte ◽  
Guilherme Mariz Maia ◽  
Paulo Matos ◽  
...  
Keyword(s):  
Immune Response ◽  
Gastrointestinal Tract ◽  
Visceral Leishmaniasis ◽  
Intestinal Bacteria ◽  
Duodenal Mucosa ◽  
Control Group ◽  
Tnf Α ◽  
Organ Specific ◽  
Ifn Γ

INTRODUCTION: Visceral leishmaniasis (VL) is a neglected tropical disease with a complex immune response in different organs. This pattern of organ-specific immune response has never been evaluated in the gastrointestinal tract. The aim of this study was to determine the in situ immune response in duodenal biopsies on patients with VL. METHODS: A case-control study was conducted on 13 patients with VL in comparison with nine controls. The immune response was evaluated using immunohistochemistry, for CD4, CD8, CD68, IL-4, IFN-γ, TNF-α and IL-10. Histological findings from the villi, crypts and inflammatory process were analyzed. RESULTS: All the cases of VL presented Leishmania antigens. No antigen was detected in the control group. The villus size was greater in the VL patients (p < 0.05). CD68 (macrophages) and CD4 levels were higher in the VL patients (p < 0.05). No differences in the expression of CD8, TNF-α, IL-10 or IL-4 were demonstrated. The number of cells expressing IFN-γ was lower in the VL patients (p < 0.05). CONCLUSIONS: Low levels of cytokines were found in the gastrointestinal tract of patients with VL. This pattern was not found in other organs affected by the disease. Immunotolerance of this tissue against Leishmania could explain these findings, as occurs with intestinal bacteria.

scholarly journals Laboratory findings in SARS-CoV-2 infections: State of the art

2020 ◽  
Vol 66 (8) ◽  
pp. 1152-1156 ◽  
Author(s):  
Miguel Augusto Martins Pereira ◽  
Isabella Carolina de Almeida Barros ◽  
Ana Luiza Veríssimo Jacob ◽  
Mayara Lopes de Assis ◽  
Salim Kanaan ◽  
...  
Keyword(s):  
State Of The Art ◽  
Case Definitions ◽  
Laboratory Findings ◽  
Laboratory Markers ◽  
Tnf Α ◽  
The Subject ◽  
Ifn Γ ◽  
High Level ◽  
Laboratory Changes ◽  
Worse Prognosis

SUMMARY OBJECTIVE The scientific community is constantly assessing the clinical and laboratory manifestations of COVID-19 in the organism. In view of the fragmentation of the large amount of information, knowledge gaps in relation to laboratory markers, and scarcity of papers in Portuguese, we propose a Literature review on laboratory changes observed in patients infected with SARS-CoV-2. METHODS Analysis of articles published between December 2019 and May 2020 on the PubMed and SciELO databases. The articles were identified, filtered, and evaluated based on the approach to the subject, language, and impact. Then, the articles were subjected to a thorough reading, in full, by 4 (four) independent researchers. RESULTS Leukopenia and lymphopenia were included in most studies, even in case definitions. Platelet count and platelet-lymphocyte ratio, at peak platelet, were associated with advanced age and longer hospital stay. Eosinopenia showed a sensitivity of 74.7% and specificity of 68.7% and, together with increased CRP, these are one of the future prospects for screening for disease. A high level of procalcitonin may indicate bacterial co-infection, leading to a worse prognosis. COVID-19 manifests itself with increased levels of many inflammatory markers such as IL-1, IL-2, IL-6, IL-7, IL-12, IP10, IFN-γ, MIP1A, MCP1, GSCF, TNF-α, and MCP1/CCL2, as well as LDH, ESR, D-dimer, CK, ALT, and AST. CONCLUSION There is a need for further studies on the new SARS-CoV-2. So far, there is no consensus regarding laboratory findings and their usefulness, whether as a prognostic marker, mortality, or disease severity.

scholarly journals Quest for Correlates of Protection against Tuberculosis

2015 ◽  
Vol 22 (3) ◽  
pp. 258-266 ◽  
Author(s):  
Kamlesh Bhatt ◽  
Sheetal Verma ◽  
Jerrold J. Ellner ◽  
Padmini Salgame
Keyword(s):  
T Cells ◽  
Vaccine Development ◽  
Interleukin 2 ◽  
T Cell Response ◽  
Content Type ◽  
Alternative Pathways ◽  
Correlates Of Protection ◽  
Human Immune Response ◽  
Ifn Γ ◽  
High Level

ABSTRACTA major impediment to tuberculosis (TB) vaccine development is the lack of reliable correlates of immune protection or biomarkers that would predict vaccine efficacy. Gamma interferon (IFN-γ) produced by CD4+T cells and, recently, multifunctional CD4+T cells secreting IFN-γ, tumor necrosis factor (TNF), and interleukin-2 (IL-2) have been used in vaccine studies as a measurable immune parameter, reflecting activity of a vaccine and potentially predicting protection. However, accumulating experimental evidence suggests that host resistance againstMycobacterium tuberculosisinfection is independent of IFN-γ and TNF secretion from CD4+T cells. Furthermore, the booster vaccine MVA85A, despite generating a high level of multifunctional CD4+T cell response in the host, failed to confer enhanced protection in vaccinated subjects. These findings suggest the need for identifying reliable correlates of protection to determine the efficacy of TB vaccine candidates. This article focuses on alternative pathways that mediateM. tuberculosiscontrol and their potential for serving as markers of protection. The review also discusses the significance of investigating the natural human immune response toM. tuberculosisto identify the correlates of protection in vaccination.

scholarly journals Fusion Cytokines IL-7-Linker-IL-15 Promote Mycobacterium Tuberculosis Subunit Vaccine to Induce Central Memory like T Cell-Mediated Immunity

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 715
Author(s):  
Chunxiang Bai ◽  
Lijun Zhou ◽  
Junxia Tang ◽  
Juanjuan He ◽  
Jiangyuan Han ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Protective Efficacy ◽  
Central Memory ◽  
Control Group ◽  
Cell Mediated Immunity ◽  
Protein Subunit ◽  
Subunit Vaccines ◽  
Ifn Γ

Tuberculosis (TB), caused by Mycobacterium tuberculosis (M. tuberculosis), is among the most serious infectious diseases worldwide. Adjuvanted protein subunit vaccines have been demonstrated as a kind of promising novel vaccine. This study proposed to investigate whether cytokines interliukine-7 (IL-7) and interliukine-15 (IL-15) help TB subunit vaccines induce long-term cell-mediated immune responses, which are required for vaccination against TB. In this study, mice were immunized with the M. tuberculosis protein subunit vaccines combined with adnovirus-mediated cytokines IL-7, IL-15, IL-7-IL-15, and IL-7-Linker-IL-15 at 0, 2, and 4 weeks, respectively. Twenty weeks after the last immunization, the long-term immune responses, especially the central memory-like T cells (TCM like cell)-mediated immune responses, were determined with the methods of cultured IFN-γ-ELISPOT, expanded secondary immune responses, cell proliferation, and protective efficacy against Mycobacterium bovis Bacilli Calmette-Guerin (BCG) challenge, etc. The results showed that the group of vaccine + rAd-IL-7-Linker-IL-15 induced a stronger long-term antigen-specific TCM like cells-mediated immune responses and had higher protective efficacy against BCG challenge than the vaccine + rAd-vector control group, the vaccine + rAd-IL-7 and the vaccine + rAd-IL-15 groups. This study indicated that rAd-IL-7-Linker-IL-15 improved the TB subunit vaccine’s efficacy by augmenting TCM like cells and provided long-term protective efficacy against Mycobacteria.

scholarly journals A Wearable and Deformable Graphene-Based Affinity Nanosensor for Monitoring of Cytokines in Biofluids

Nanomaterials ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1503 ◽  
Author(s):  
Ziran Wang ◽  
Zhuang Hao ◽  
Shifeng Yu ◽  
Cong Huang ◽  
Yunlu Pan ◽  
...  
Keyword(s):  
Human Body ◽  
Large Deformations ◽  
Time Resolved ◽  
Cytokine Detection ◽  
Planar Surfaces ◽  
Tnf Α ◽  
Mechanical Durability ◽  
Ifn Γ ◽  
High Level ◽  
Modified Graphene

A wearable and deformable graphene-based field-effect transistor biosensor is presented that uses aptamer-modified graphene as the conducting channel, which is capable of the sensitive, consistent and time-resolved detection of cytokines in human biofluids. Based on an ultrathin substrate, the biosensor offers a high level of mechanical durability and consistent sensing responses, while conforming to non-planar surfaces such as the human body and withstanding large deformations (e.g., bending and stretching). Moreover, a nonionic surfactant is employed to minimize the nonspecific adsorption of the biosensor, hence enabling cytokine detection (TNF-α and IFN-γ, significant inflammatory cytokines, are used as representatives) in artificial tears (used as a biofluid representative). The experimental results demonstrate that the biosensor very consistently and sensitively detects TNF-α and IFN-γ, with limits of detection down to 2.75 and 2.89 pM, respectively. The biosensor, which undergoes large deformations, can thus potentially provide a consistent and sensitive detection of cytokines in the human body.

Study on Mechanism of Human Marrow Mesenchymal Stem Cell in Treating Patients with Aplastic Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4099-4099
Author(s):  
Zhenhua Qiao ◽  
Xiujuan Zhao
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
T Cells ◽  
Aplastic Anemia ◽  
Hematopoietic Cell ◽  
Control Group ◽  
Rt Pcr ◽  
Tnf Α ◽  
Ifn Γ ◽  
Tgf Β1

Abstract Objective: To explore mechanism of human marrow mesenchymal stem cells (MSCs) in treating patients with aplastic anemia(AA). Methods: MSCs in patients with aplastic anemia(AA) and the control group were separated with Percoll(1.073g/m L) and cultured in low glucose DMEM. Then, observed their morphologies,checked their molecule surface antigen by flow cytometry and examined the process of adipogenic differention. The mononuclear cells (MNC)of marrow in patients with AA were enriched based 1.077g/L density centrifuge and cultured in the 1640 medium. (1)MSC in control group and MNC in AA group were co-cultured with or without cytokines. The function of supporting hematopoiesis for MSC was to be observed in single confluence layer after plating by counting the total cells and the clones in every well every week. Then analyzed the dynamics of proliferation. T cells were harvested by using nylon column. MSC in control group and T cells in AA group were co-cultured. The proliferation of T cell was measured by MTT method. The CD25,CD69,CD4,CD8,Annexin-V expression rates of CD3+T cells were analyzed by flow cytometry .The gene and protein of IL-2, IL-4,IL-10,TNF-α,IFN-γ,TGF-β1 were examined by RT-PCR and ELISA respectively. MSC treated to the model of AA, by the examination of peripheral hemogram, bone marrow biopsy, pathological section of spleen. Results: There was no significant difference between control group MSC and AA-MSC in morphologies but adipogenic differentiation in AA patients is earlier than controls. The clones of CFU-GM in group(MSC)(78.46±3.58)/2×105 cells, after 14 days cultured was significantly higher than(9.21±4.32)/2×105 cells in group(CK + DMEM medium), while lower than (99.32±4.34)/2×105 cells in group(MSC+CK). (1)the Treg cells (TCD4+CD25+) in AA group (2.01±1.21)/ 2×105 was significantly lower than (4.43±1.67)/2×105 cells in control group, while(5.43±2.31) / 2×105 in group (MSC+AAT) was no more than (4.43±1.67)/2×105 cells in control group. (2) MSCs significantly inhibited T cell proliferation (P< 0. O5)by MTT. (3) RT-PCR and ELISA analysis showed that MSCs induced the expression of IL-4, IL-10, TGF-β1 and decreased significantly the expression of IL-2, TNF-α, IFN -γ in T cells of AA. the model of AA treated by MSCs showed improvements in 3 blood components greatly(p<0.05), Bone marrow proliferated and restored to the normal level, hematopoietic cell increased obviously (hematopoietic cell capacity was more than 40%), and atrophied spleen restore to normality. Conclusions: morphologies of AA’MSC had no evident different with the control but was more easy adipogenic differention. aplastic anemia belongs to autoimmune diseases in which T cells effect organ-specific destruction. The fundamental mechanism of MSC in treating AA should be potential to promote hematopoietic cell proliferation by adjusting immunity.

Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li
Keyword(s):  
Plasma Concentration ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Control Group ◽  
Gene Expressions ◽  
Expression Levels ◽  
Tnf Α ◽  
Healthy Control ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

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