Pub Date : 2022-09-01DOI: 10.22034/iji.2022.93726.2250
Alireza Norouzi, Shohreh Taziki, Ali Najafipasandi, Saeed Mohammadi, Gholamreza Roshandel
Background: Natural killer (NK) cells are dichotomously involved in chronic hepatitis B (CHB) infection as principal members of innate immunity. An effective treatment should enhance the antiviral potentials of NK cells and not their immunomodulatory roles. TIM-3 (T-cell immunoglobulin and mucin-containing domain) is a molecule with an essential role in controlling immune tolerance. TIM-3 demonstrated the highest expression among NK cells of patients with chronic liver disorders. Statins have been reported to attenuate the levels of TIM-3 on NK cells.
Objectives: To investigate the frequencies of NK cells, NKT cells, and TIM-3+ population in patients with CHB upon rosuvastatin (RSV) intervention.
Methods: Thirty confirmed patients with CHB were randomly assigned into two groups of 15 (receiving 20 mg of RSV or placebo per day) for 12 weeks. We evaluated the percentages of TIM-3+ cells by staining the peripheral blood mononuclear cells (PBMCs) with CD3, CD16, and CD56 markers using flow cytometry.
Results: Our findings indicated that RSV administration could increase CD3- CD56+ NK cells (P>0.05) and CD3+ CD16+ CD56+ NKT cells (P<0.05). RSV intervention could reduce the percentages of TIM-3+ cells among NK cells (P<0.01) and NKT cells (P> 0.05) of patients with CHB compared with the placebo group.
Conclusions: The increased population of NK and NKT cells and the effective reduction of TIM-3+ cells among patients with CHB delineated that rosuvastatin could be proposed as an appropriate modulator of innate immune response (regarding NK and NKT cells) in favor of enhancing their antiviral activities.
{"title":"Rosuvastatin Intervention Decreased the Frequencies of the TIM-3+ Population of NK Cells and NKT Cells among Patients with Chronic Hepatitis B.","authors":"Alireza Norouzi, Shohreh Taziki, Ali Najafipasandi, Saeed Mohammadi, Gholamreza Roshandel","doi":"10.22034/iji.2022.93726.2250","DOIUrl":"https://doi.org/10.22034/iji.2022.93726.2250","url":null,"abstract":"<p><strong>Background: </strong>Natural killer (NK) cells are dichotomously involved in chronic hepatitis B (CHB) infection as principal members of innate immunity. An effective treatment should enhance the antiviral potentials of NK cells and not their immunomodulatory roles. TIM-3 (T-cell immunoglobulin and mucin-containing domain) is a molecule with an essential role in controlling immune tolerance. TIM-3 demonstrated the highest expression among NK cells of patients with chronic liver disorders. Statins have been reported to attenuate the levels of TIM-3 on NK cells.</p><p><strong>Objectives: </strong>To investigate the frequencies of NK cells, NKT cells, and TIM-3+ population in patients with CHB upon rosuvastatin (RSV) intervention.</p><p><strong>Methods: </strong>Thirty confirmed patients with CHB were randomly assigned into two groups of 15 (receiving 20 mg of RSV or placebo per day) for 12 weeks. We evaluated the percentages of TIM-3+ cells by staining the peripheral blood mononuclear cells (PBMCs) with CD3, CD16, and CD56 markers using flow cytometry.</p><p><strong>Results: </strong>Our findings indicated that RSV administration could increase CD3- CD56+ NK cells (P>0.05) and CD3+ CD16+ CD56+ NKT cells (P<0.05). RSV intervention could reduce the percentages of TIM-3+ cells among NK cells (P<0.01) and NKT cells (P> 0.05) of patients with CHB compared with the placebo group.</p><p><strong>Conclusions: </strong>The increased population of NK and NKT cells and the effective reduction of TIM-3+ cells among patients with CHB delineated that rosuvastatin could be proposed as an appropriate modulator of innate immune response (regarding NK and NKT cells) in favor of enhancing their antiviral activities.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.22034/iji.2022.93951.2267
Amir Hossein Norooznezhad, Alireza A Shamshirsaz, Sedigheh Hantoushzadeh
Pregnant women with coronavirus disease 2019 (COVID-19) have a higher risk of morbidity and mortality compared with the general population. Possible pathways are: I) in patients with COVID-19, cytokine storm defined as the excess release of pro-inflammatory cytokines such as interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) has been associated with morbidities and an even higher rate of mortality. II) Labor, despite being a term/preterm, has an inflammatory nature, although, inflammation is more prominent in preterm delivery. During labor, different pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are involved which as mentioned, all are crucial role players in the cytokine storm. III) Tissue injury, and during labor, (especially cesarean section) is shown to cause inflammation via pro-inflammatory cytokines release including those involved in the cytokine storm through the activation of nuclear factor κB (NFκB). IV) post-partum hemorrhage with a notable amount of blood loss which can cause significant hypoxemia. In this condition, hypoxia-inducible factor 1α which has a cross-talk with NFκB, leads to the expression of IL-1β, IL-6, and TNF-α as both angiogenic and pro-inflammatory factors. Considering all the mentioned issues and pathways, we suggest that clinicians be careful about the escalation of the inflammatory status in their pregnant COVID-19 patients during/following labor.
{"title":"Labor Could Increase Systemic Inflammation and Cause or Deteriorate Cytokine Storm in COVID-19.","authors":"Amir Hossein Norooznezhad, Alireza A Shamshirsaz, Sedigheh Hantoushzadeh","doi":"10.22034/iji.2022.93951.2267","DOIUrl":"https://doi.org/10.22034/iji.2022.93951.2267","url":null,"abstract":"<p><p>Pregnant women with coronavirus disease 2019 (COVID-19) have a higher risk of morbidity and mortality compared with the general population. Possible pathways are: I) in patients with COVID-19, cytokine storm defined as the excess release of pro-inflammatory cytokines such as interleukin 1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α) has been associated with morbidities and an even higher rate of mortality. II) Labor, despite being a term/preterm, has an inflammatory nature, although, inflammation is more prominent in preterm delivery. During labor, different pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are involved which as mentioned, all are crucial role players in the cytokine storm. III) Tissue injury, and during labor, (especially cesarean section) is shown to cause inflammation via pro-inflammatory cytokines release including those involved in the cytokine storm through the activation of nuclear factor κB (NFκB). IV) post-partum hemorrhage with a notable amount of blood loss which can cause significant hypoxemia. In this condition, hypoxia-inducible factor 1α which has a cross-talk with NFκB, leads to the expression of IL-1β, IL-6, and TNF-α as both angiogenic and pro-inflammatory factors. Considering all the mentioned issues and pathways, we suggest that clinicians be careful about the escalation of the inflammatory status in their pregnant COVID-19 patients during/following labor.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Vaccines are the most effective way to prevent Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2).
Objectives: To compare the antibody response of healthy individuals vaccinated with either the AstraZeneca (ChAdOx1 nCoV-19) or the Sinopharm (BBIBP-CorV) vaccine, in those who had no prior infection with SARS-CoV-2.
Methods: Thirty seven participants were included, of which 17 were administered the AstraZeneca (ChAdOx1 nCoV-19) vaccine, while 20 were given the Sinopharm (BBIBP-CorV) vaccine. SARS-CoV-2 neutralizing antibody and anti-receptor-binding domain (RBD) IgG levels were checked 4 weeks after giving the first and the second dose of either vaccine using the enzyme-linked immunosorbent assay (ELISA) technique.
Results: The AstraZeneca (ChAdOx1 nCoV-19) vaccine exhibited a higher levels of anti-(RBD) IgG compared with the Sinopharm (BBIBP-CorV) in both the first (14.51 μg/ml vs. 1.160 μg/ml) and the second (46.68 μg/ml vs. 11.43 μg/ml) doses. About neutralizing Abs, the titer of the antibody was higher in the AstraZeneca (ChAdOx1 nCoV-19) recipients than in the Sinopharm (BBIBP-CorV) subjects after the first (7.77 μg/ml vs. 1.79 μg/ml, p < 0.0001) and the second dose (10. 36 μg/ml vs. 4.88 μg/ml, p < 0.0001).
Conclusions: Recipients vaccinated with two doses of the AstraZeneca (ChAdOx1 nCoV-19) had superior quantitative antibody levels than Sinopharm (BBIBP-CorV)-vaccinated subjects. These data suggest that a booster dose may be needed for the Sinopharm (BBIBP-CorV) recipients, to control the COVID-19 pandemic.
背景:疫苗是预防冠状病毒2型严重急性呼吸综合征(SARS-CoV-2)最有效的方法。目的:比较既往未感染SARS-CoV-2的健康人接种阿斯利康(ChAdOx1 nCoV-19)或国药(BBIBP-CorV)疫苗后的抗体反应。方法:纳入37例受试者,其中阿斯利康(ChAdOx1) nCoV-19疫苗17例,国药(BBIBP-CorV)疫苗20例。采用酶联免疫吸附试验(ELISA)技术,在接种第一剂和第二剂疫苗4周后检测SARS-CoV-2中和抗体和抗受体结合域(RBD) IgG水平。结果:阿斯利康(ChAdOx1 nCoV-19)疫苗第一剂量(14.51 μg/ml vs. 1.160 μg/ml)和第二剂量(46.68 μg/ml vs. 11.43 μg/ml)的抗(RBD) IgG水平均高于国药(BBIBP-CorV)。在中和抗体方面,阿斯利康(ChAdOx1 nCoV-19)和国药(BBIBP-CorV)第一次和第二次接种后的抗体滴度分别为7.77 μg/ml和1.79 μg/ml, p < 0.0001)高于国药(BBIBP-CorV)。36 μg/ml vs. 4.88 μg/ml, p < 0.0001)。结论:两剂阿斯利康(ChAdOx1 - nCoV-19)疫苗接种者的定量抗体水平高于国药(BBIBP-CorV)疫苗接种者。这些数据表明,为了控制COVID-19大流行,可能需要对国药控股(BBIBP-CorV)接种者进行加强剂量。
{"title":"Comparison of the Antibody Responses Following Vaccination with AstraZeneca and Sinopharm.","authors":"Enayat Anvari, Atefe Ghamar Talepoor, Mahsa Eshkevar Vakili, Narges Karimi, MohammadReza Ataollahi, Gelareh Najafi, Dieter Kabalitz, Iraj Ahmadi, Kurosh Kalantar","doi":"10.22034/iji.2022.94298.2300","DOIUrl":"https://doi.org/10.22034/iji.2022.94298.2300","url":null,"abstract":"<p><strong>Background: </strong>Vaccines are the most effective way to prevent Coronavirus 2 severe acute respiratory syndrome (SARS-CoV-2).</p><p><strong>Objectives: </strong>To compare the antibody response of healthy individuals vaccinated with either the AstraZeneca (ChAdOx1 nCoV-19) or the Sinopharm (BBIBP-CorV) vaccine, in those who had no prior infection with SARS-CoV-2.</p><p><strong>Methods: </strong>Thirty seven participants were included, of which 17 were administered the AstraZeneca (ChAdOx1 nCoV-19) vaccine, while 20 were given the Sinopharm (BBIBP-CorV) vaccine. SARS-CoV-2 neutralizing antibody and anti-receptor-binding domain (RBD) IgG levels were checked 4 weeks after giving the first and the second dose of either vaccine using the enzyme-linked immunosorbent assay (ELISA) technique.</p><p><strong>Results: </strong>The AstraZeneca (ChAdOx1 nCoV-19) vaccine exhibited a higher levels of anti-(RBD) IgG compared with the Sinopharm (BBIBP-CorV) in both the first (14.51 μg/ml vs. 1.160 μg/ml) and the second (46.68 μg/ml vs. 11.43 μg/ml) doses. About neutralizing Abs, the titer of the antibody was higher in the AstraZeneca (ChAdOx1 nCoV-19) recipients than in the Sinopharm (BBIBP-CorV) subjects after the first (7.77 μg/ml vs. 1.79 μg/ml, p < 0.0001) and the second dose (10. 36 μg/ml vs. 4.88 μg/ml, p < 0.0001).</p><p><strong>Conclusions: </strong>Recipients vaccinated with two doses of the AstraZeneca (ChAdOx1 nCoV-19) had superior quantitative antibody levels than Sinopharm (BBIBP-CorV)-vaccinated subjects. These data suggest that a booster dose may be needed for the Sinopharm (BBIBP-CorV) recipients, to control the COVID-19 pandemic.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9271968","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.22034/iji.2022.89256.1934
Fawei Yuan, Huan Yin, Juan Tan, Kun Zheng, Xiping Mei, Lixue Yuan
Background: Sepsis is a serious condition with a high mortality rate, and septic patients often have organ dysfunction, low tissue perfusion and hypoxia, lactic acidosis, oliguria, or functional brain changes.
Objective: To observe the number and the function of Vδ1T cells in peripheral blood of septic patients, to analyze the clinical significance of detecting Vδ1T cells, and to clarify the correlation of their presence with the prognosis of sepsis.
Methods: The basic data of the septic patients were recorded at admission. The immunosuppressive function-related molecules on the surface of Vδ1T cells were detected, and the immunosuppressive function of Vδ1T cells was also evaluated.
Results: Compared with the healthy controls, the proportion of Vδ1T cells in the blood of septic patients significantly decreased (P<0.01). The proportion of Vδ1T cells in septic patients correlated with the patients' condition (P<0.05). The expression of glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) on the surface of Vδ1T cells in the blood of septic patients significantly increased (P<0.01). The increase of Vδ1T cells in septic patients had inhibitory effects on T cell proliferation and interferon (IFN)-γ secretion. These findings implied that the immunosuppression of Vδ1Tcells in the peripheral blood of septic patients was significantly higher than that of the healthy controls (P<0.01).
Conclusion: Changes in Vδ1T cells in septic patients were closely related to the patient's condition and prognosis.
{"title":"The Proportion of Vδ1T Cells in Peripheral Blood Correlated with Prognosis of Sepsis.","authors":"Fawei Yuan, Huan Yin, Juan Tan, Kun Zheng, Xiping Mei, Lixue Yuan","doi":"10.22034/iji.2022.89256.1934","DOIUrl":"https://doi.org/10.22034/iji.2022.89256.1934","url":null,"abstract":"<p><strong>Background: </strong>Sepsis is a serious condition with a high mortality rate, and septic patients often have organ dysfunction, low tissue perfusion and hypoxia, lactic acidosis, oliguria, or functional brain changes.</p><p><strong>Objective: </strong>To observe the number and the function of Vδ1T cells in peripheral blood of septic patients, to analyze the clinical significance of detecting Vδ1T cells, and to clarify the correlation of their presence with the prognosis of sepsis.</p><p><strong>Methods: </strong>The basic data of the septic patients were recorded at admission. The immunosuppressive function-related molecules on the surface of Vδ1T cells were detected, and the immunosuppressive function of Vδ1T cells was also evaluated.</p><p><strong>Results: </strong>Compared with the healthy controls, the proportion of Vδ1T cells in the blood of septic patients significantly decreased (P<0.01). The proportion of Vδ1T cells in septic patients correlated with the patients' condition (P<0.05). The expression of glucocorticoid-induced tumor necrosis factor receptor (GITR), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) on the surface of Vδ1T cells in the blood of septic patients significantly increased (P<0.01). The increase of Vδ1T cells in septic patients had inhibitory effects on T cell proliferation and interferon (IFN)-γ secretion. These findings implied that the immunosuppression of Vδ1Tcells in the peripheral blood of septic patients was significantly higher than that of the healthy controls (P<0.01).</p><p><strong>Conclusion: </strong>Changes in Vδ1T cells in septic patients were closely related to the patient's condition and prognosis.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40393012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.22034/iji.2022.90031.1985
Yu Xia Zhao, Hong Mei, Yang Xin Huang, Jia Qing Chen
Background: The negative feedback circuit NIK-SIN could inhibit the systemic inflammation and protect mouse from endotoxic shock. However, the physiological significance of NIK-SIX feedback circuit in the maintenance of intestinal immune homeostasis and prevention of early-onset spontaneous colitis is not known.
Objective: To explore the role of NIK-SIX axis in the maintenance of intestinal immune homeostasis.
Methods: The conditional knockout of NIK encoding gene, Map3k14, in the Cd11c+ dendritic cells were generated by crossing Map3k14-flox mice with Cd11c-Cre mice. DSS was used for colitis models. The expression of cytokines in the intestinal immune cells, isolated from Map3k14-cKO mice were detected by qPCR. The siRNA molecules were used for the silencing of SIN-proteins. Then luciferase assays and chromatin immunoprecipitation combined with qPCR were applied for mechanism investigations.
Results: The expression of SIX1 and SIX2 protein in BMDMs from WT were significantly lower than in the Map3k14-cKO mice. In vitro, the NIK-/- human-derived circulating monocytes also failed to express SIX-proteins under the stimulation of non-canonical NF-κB agonists. The expression of cytokines was significantly decreased in human circulating monocytes with overexpression SIN-proteins. The expression of cytokines in macrophages, DCs and T cells isolated from Map3k14-cKO mice were significantly increased in the DSS-induced models. Higher expression of cytokines was observed in the SIN1-/- and SIN2-/- cells including human circulating monocytes, mouse-derived BMDMs, intestinal macrophages and DCs. SIN-proteins directly bound the promoter region of inflammatory genes.
Conclusion: NIK-SIX axis down-regulated inflammatory gene expression and plays a pivotal role in the maintenance of intestinal immune homeostasis.
{"title":"Impairment of a NIK-SIX Feedback Axis Results in Dysregulation of Intestinal Immune Homeostasis and Promotes Early-onset Fatal Spontaneous Colitis.","authors":"Yu Xia Zhao, Hong Mei, Yang Xin Huang, Jia Qing Chen","doi":"10.22034/iji.2022.90031.1985","DOIUrl":"10.22034/iji.2022.90031.1985","url":null,"abstract":"<p><strong>Background: </strong>The negative feedback circuit NIK-SIN could inhibit the systemic inflammation and protect mouse from endotoxic shock. However, the physiological significance of NIK-SIX feedback circuit in the maintenance of intestinal immune homeostasis and prevention of early-onset spontaneous colitis is not known.</p><p><strong>Objective: </strong>To explore the role of NIK-SIX axis in the maintenance of intestinal immune homeostasis.</p><p><strong>Methods: </strong>The conditional knockout of NIK encoding gene, Map3k14, in the Cd11c+ dendritic cells were generated by crossing Map3k14-flox mice with Cd11c-Cre mice. DSS was used for colitis models. The expression of cytokines in the intestinal immune cells, isolated from Map3k14-cKO mice were detected by qPCR. The siRNA molecules were used for the silencing of SIN-proteins. Then luciferase assays and chromatin immunoprecipitation combined with qPCR were applied for mechanism investigations.</p><p><strong>Results: </strong>The expression of SIX1 and SIX2 protein in BMDMs from WT were significantly lower than in the Map3k14-cKO mice. In vitro, the NIK-/- human-derived circulating monocytes also failed to express SIX-proteins under the stimulation of non-canonical NF-κB agonists. The expression of cytokines was significantly decreased in human circulating monocytes with overexpression SIN-proteins. The expression of cytokines in macrophages, DCs and T cells isolated from Map3k14-cKO mice were significantly increased in the DSS-induced models. Higher expression of cytokines was observed in the SIN1-/- and SIN2-/- cells including human circulating monocytes, mouse-derived BMDMs, intestinal macrophages and DCs. SIN-proteins directly bound the promoter region of inflammatory genes.</p><p><strong>Conclusion: </strong>NIK-SIX axis down-regulated inflammatory gene expression and plays a pivotal role in the maintenance of intestinal immune homeostasis.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-09-01DOI: 10.22034/iji.2022.92641.2162
Luis Antonio Ochoa-Ramirez, Rosalio Ramos-Payan, German Reynaldo Jimenez-Gastelum, Jose Rodriguez-Millan, Maribel Aguilar-Medina, Juan Jose Rios-Tostado, Alfredo Ayala-Ham, Mercedez Bermudez, Juan Fidel Osuna-Ramos, Vicente Olimon-Andalon, Jesús Salvador Velarde-Félix
Background: Coronavirus disease 2019 (COVID-19) is an emergent viral disease in which the host inflammatory response modulates the clinical outcome. Severe outcomes are associated with an exacerbation of inflammation in which chemokines play an important role as the attractants of immune cells to the tissues.
Objective: To evaluate the relationship of the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10 with COVID-19 severity and outcomes in Mexican patients.
Methods: We analyzed the serum levels of IL-8, RANTES, MIG, MCP-1 and IP-10 in 148 COVID-19 hospitalized patients classified as mild (n=20), severe (n=61), and critical (n=67), as well as in healthy individuals (n=10), by flow cytometry bead array assay.
Results: Chemokine levels were higher in patients than in the healthy individuals, but only MIG, MCP-1, and IP-10 increased according to the disease severity, showing the highest levels in the critical group. MIG, MCP-1, and IP-10 levels were also higher in COVID-19 patients with comorbidities such as renal disease, type 2 diabetes, and hypertension. Moreover, elevated MIG levels seem to be related to organic failure/shock, and an increased risk of death.
Conclusions: Our results suggest that the increased levels of MCP-1, IP-10, and especially MIG might be useful in predicting severe COVID-19 outcomes and could be promising therapeutic targets.
{"title":"The Chemokine MIG is Associated with an Increased Risk of COVID-19 Mortality in Mexican Patients.","authors":"Luis Antonio Ochoa-Ramirez, Rosalio Ramos-Payan, German Reynaldo Jimenez-Gastelum, Jose Rodriguez-Millan, Maribel Aguilar-Medina, Juan Jose Rios-Tostado, Alfredo Ayala-Ham, Mercedez Bermudez, Juan Fidel Osuna-Ramos, Vicente Olimon-Andalon, Jesús Salvador Velarde-Félix","doi":"10.22034/iji.2022.92641.2162","DOIUrl":"https://doi.org/10.22034/iji.2022.92641.2162","url":null,"abstract":"<p><strong>Background: </strong>Coronavirus disease 2019 (COVID-19) is an emergent viral disease in which the host inflammatory response modulates the clinical outcome. Severe outcomes are associated with an exacerbation of inflammation in which chemokines play an important role as the attractants of immune cells to the tissues.</p><p><strong>Objective: </strong>To evaluate the relationship of the chemokines IL-8, RANTES, MIG, MCP-1, and IP-10 with COVID-19 severity and outcomes in Mexican patients.</p><p><strong>Methods: </strong>We analyzed the serum levels of IL-8, RANTES, MIG, MCP-1 and IP-10 in 148 COVID-19 hospitalized patients classified as mild (n=20), severe (n=61), and critical (n=67), as well as in healthy individuals (n=10), by flow cytometry bead array assay.</p><p><strong>Results: </strong>Chemokine levels were higher in patients than in the healthy individuals, but only MIG, MCP-1, and IP-10 increased according to the disease severity, showing the highest levels in the critical group. MIG, MCP-1, and IP-10 levels were also higher in COVID-19 patients with comorbidities such as renal disease, type 2 diabetes, and hypertension. Moreover, elevated MIG levels seem to be related to organic failure/shock, and an increased risk of death.</p><p><strong>Conclusions: </strong>Our results suggest that the increased levels of MCP-1, IP-10, and especially MIG might be useful in predicting severe COVID-19 outcomes and could be promising therapeutic targets.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Periodontal diseases originate from a group of oral inflammatory infections initiated by oral pathogens. Among these pathogens, Gram-negative bacteria such as p. gingivalis play a major role in chronic periodontitis. P. gingivalis harbours lipopolysaccharide (LPS) which enables it to attach to TLR2.
Objectives: Evaluating the effects of P. gingivalis and E. coli LPS on the gene expression of TLRs and inflammatory cytokines in human dental pulp stem cells (hDPSCs).
Methods: We evaluated the expression level of TLR2, TLR4, IL-6, IL-10, and 1L-18 in hDPSCs treated with 1μg/mL of P. gingivalis lipopolysaccharide and E. coli LPS at three different exposure times using Real-time RT-PCR.
Result: The test group treated with P. gingivalis LPS showed a high level of TLR4 expression in 24 hours exposure period and the lowest expression in 48 hours of exposure time. In the case of IL-10, the lowest expression was in the 24 hours exposure period. Although in the E.coli LPS treated group, IL-10 showed the highest expression in 24 and lowest in 48 hours exposure period. Moreover, IL-18 in P. gingivalis LPS treated group showed a significant difference between 6, 24, and 48-time periods of exposure, but not in the E. coli LPS treated group.
Conclusion: Both types of LPS stimulate inflammation through TLR4 expression. P. gingivalis LPS performs more potentially than E. coli in terms of stimulating inflammation at the first 24 hours of exposure. Nevertheless, our study confirmed that increasing P. gingivalis and/or the E.coli LPS exposure time, despite acting as an inflammatory stimulator, apparently showed anti-inflammatory properties.
背景:牙周病起源于口腔病原体引起的一组口腔炎症感染。在这些病原体中,革兰氏阴性菌如牙龈假单胞菌在慢性牙周炎中起主要作用。牙龈卟啉卟啉含有脂多糖(LPS),使其能够附着在TLR2上。目的:探讨牙龈卟啉卟啉和大肠杆菌脂多糖对人牙髓干细胞(hDPSCs) TLRs基因表达和炎症因子表达的影响。方法:采用Real-time RT-PCR检测1μg/mL牙龈假单胞菌脂多糖和大肠杆菌脂多糖处理hdpsc时,TLR2、TLR4、IL-6、IL-10和1L-18在三种不同暴露时间下的表达水平。结果:试验组暴露24 h TLR4表达水平较高,暴露48 h TLR4表达水平最低。IL-10在24小时内表达量最低。而在大肠杆菌LPS处理组,IL-10在24小时内表达量最高,在48小时内表达量最低。此外,IL-18在牙龈卟啉单胞菌LPS处理组暴露6、24和48个时间段之间表现出显著差异,而在大肠杆菌LPS处理组则无显著差异。结论:两种LPS均通过TLR4表达刺激炎症反应。在暴露的最初24小时内,牙龈卟啉卟啉脂多糖比大肠杆菌更有可能刺激炎症。然而,我们的研究证实,增加牙龈假单胞菌和/或大肠杆菌LPS暴露时间,尽管作为炎症刺激剂,但明显表现出抗炎特性。
{"title":"Effects of Lipopolysaccharide from Porphyromonas gingivalis and Escherichia coli on Gene Expression Levels of Toll-like Receptors and Inflammatory Cytokines in Human Dental Pulp Stem Cells.","authors":"Hanieh Mojtahedi, Nikoo Hossein-Khannazer, Seyed Mahmoud Hashemi, Mina Masoudnia, Monireh Askarzadeh, Arash Khojasteh, Mandana Sattari","doi":"10.22034/iji.2022.92223.2136","DOIUrl":"https://doi.org/10.22034/iji.2022.92223.2136","url":null,"abstract":"<p><strong>Background: </strong>Periodontal diseases originate from a group of oral inflammatory infections initiated by oral pathogens. Among these pathogens, Gram-negative bacteria such as p. gingivalis play a major role in chronic periodontitis. P. gingivalis harbours lipopolysaccharide (LPS) which enables it to attach to TLR2.</p><p><strong>Objectives: </strong>Evaluating the effects of P. gingivalis and E. coli LPS on the gene expression of TLRs and inflammatory cytokines in human dental pulp stem cells (hDPSCs).</p><p><strong>Methods: </strong>We evaluated the expression level of TLR2, TLR4, IL-6, IL-10, and 1L-18 in hDPSCs treated with 1μg/mL of P. gingivalis lipopolysaccharide and E. coli LPS at three different exposure times using Real-time RT-PCR.</p><p><strong>Result: </strong>The test group treated with P. gingivalis LPS showed a high level of TLR4 expression in 24 hours exposure period and the lowest expression in 48 hours of exposure time. In the case of IL-10, the lowest expression was in the 24 hours exposure period. Although in the E.coli LPS treated group, IL-10 showed the highest expression in 24 and lowest in 48 hours exposure period. Moreover, IL-18 in P. gingivalis LPS treated group showed a significant difference between 6, 24, and 48-time periods of exposure, but not in the E. coli LPS treated group.</p><p><strong>Conclusion: </strong>Both types of LPS stimulate inflammation through TLR4 expression. P. gingivalis LPS performs more potentially than E. coli in terms of stimulating inflammation at the first 24 hours of exposure. Nevertheless, our study confirmed that increasing P. gingivalis and/or the E.coli LPS exposure time, despite acting as an inflammatory stimulator, apparently showed anti-inflammatory properties.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently in a review article by Mansourabadi et al. published in the Iranian Journal of Immunology, the authors described the serological and molecular tests for COVID-19 (1). The mentioned review considered helicase (Hel) as a structural protein of SARS-CoV-2 (1). However, based on evidence, the genome of novel coronavirus is approximately 30kb in length and encodes only four structural proteins, including spike (S), envelope (E), membrane (M), and nucleoprotein (N) (2, 3), although helicase (NSP13) as a nonstructural protein such as RNA-dependent RNA polymerases (NSP12) encoded by the ORF region and is involved in the replication of the virus (3).In addition, authors reported that hemagglutinin esterase could be used as a favorite target for SARS-CoV-2 Real-time PCR (1); however, scientific evidence shows that SARS-CoV-2 as a betacoronavirus lineage B like SARS-CoV lacks hemagglutinin esterase (4-6); thus this protein cannot be a target for detection of SARS-CoV-2.
{"title":"Letter to the Editor Regarding \"An Overview on Serology and Molecular Tests for COVID-19: An Important Challenge of the Current Century (doi: 10.22034/iji.2021.88660.1894.)\".","authors":"Milad Zandi, Emad Behboudi, Mohammad Reza Shojaei, Saber Soltani, Hassan Karami","doi":"10.22034/iji.2022.91791.2107","DOIUrl":"https://doi.org/10.22034/iji.2022.91791.2107","url":null,"abstract":"<p><p>Recently in a review article by Mansourabadi et al. published in the Iranian Journal of Immunology, the authors described the serological and molecular tests for COVID-19 (1). The mentioned review considered helicase (Hel) as a structural protein of SARS-CoV-2 (1). However, based on evidence, the genome of novel coronavirus is approximately 30kb in length and encodes only four structural proteins, including spike (S), envelope (E), membrane (M), and nucleoprotein (N) (2, 3), although helicase (NSP13) as a nonstructural protein such as RNA-dependent RNA polymerases (NSP12) encoded by the ORF region and is involved in the replication of the virus (3).In addition, authors reported that hemagglutinin esterase could be used as a favorite target for SARS-CoV-2 Real-time PCR (1); however, scientific evidence shows that SARS-CoV-2 as a betacoronavirus lineage B like SARS-CoV lacks hemagglutinin esterase (4-6); thus this protein cannot be a target for detection of SARS-CoV-2.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40394430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.
Objective: This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.
Methods: Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.
Results: Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.
Conclusions: it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.
{"title":"Frequency of CD39+, LAG3+, and CTLA4+ Regulatory T Cells in Two Different Immunosuppressive Protocols in Renal Allograft Recipients (Sirolimus vs Mycophenolate mofetil): A Cohort Report.","authors":"Yaghoub Mollaei-Kandelous, Pedram Ahmadpoor, Mohsen Nafar, Mohammad Reza Khatami, Samad Farashi Bonab, Nader Tajik, Mahdi Shekarabi, Aliakbar Amirzargar","doi":"10.22034/iji.2022.92623.2161","DOIUrl":"https://doi.org/10.22034/iji.2022.92623.2161","url":null,"abstract":"<p><strong>Background: </strong>Impaired renal function is considered as a significant risk factor for cardiovascular events in chronic kidney disease patients. Several immunosuppressive drugs are used in these patients, which necessitates to minimize the drug-related side effects by employing alternative strategies.</p><p><strong>Objective: </strong>This study aimed to evaluate prospectively the influence of low dose ATG induction therapy with two different protocols (Sirolimus versus Mycophenolate mofetil) on the expression of functional markers (LAG-3, CD39, and intracellular CTLA-4) on conventional Tregs in renal recipients.</p><p><strong>Methods: </strong>Thirty-eight renal transplant recipients were enrolled in this study. The patients were randomly assigned into two groups, including TMP: Tacrolimus (Tac), Mycophenolate mofetil (MMF), and Prednisolone (n=23); and TSP: Tac, Sirolimus (SRL), and Prednisolone (n=15). The frequency of LAG-3, CD39, and intracellular CTLA-4 on circulating Tregs was analyzed by flow cytometry before and after transplantation.</p><p><strong>Results: </strong>Analysis of the flow cytometry data showed that the frequency of CD4+CD25+FOXP3+ Tregs increased 4 months post-transplantation compared to pre-transplantation in both groups, although this increase was only significant in TMP group. In TMP treated patients, the frequency of LAG-3+ Tregs and CD39+ Tregs increased, whereas the frequency of intracellular CTLA-4+ Tregs decreased 4 months post-transplantation. In TSP group, while the frequency of CD39+ Tregs increased, the frequency of CTLA-4+ Tregs decreased in post-transplantation compared to pre-transplantation.</p><p><strong>Conclusions: </strong>it seems that both treatment regimen protocols with a low dose ATG induction therapy may be clinically applicable in kidney transplant recipients.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40393011","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD.
Objectives: To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci.
Methods: A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and 394 patients with Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method.
Results: Allele C and combinational genotype AC+CC of rs3212227 within IL-23 were significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within IL-17RA were significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within IL-17F were significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (IL-23R-IL-23-IL-17RA-IL-17F-sex) was identified in AITD, GD, and HT patients with GMDR analysis.
Conclusions: Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.
背景:一些自身免疫性和炎症性疾病,包括自身免疫性甲状腺疾病(AITD),已经与Th17细胞和IL-23/IL-17轴有关。目前的数据表明,遗传变异对AITD的易感性有很大影响。目的:研究IL-23/IL-17通路单核苷酸多态性(snp)在AITD易感性中的作用,并检测这些位点的基因-基因/基因-性别相互作用。方法:纳入1051例AITD患者,其中Graves病(GD)患者657例,桥本甲状腺炎(HT)患者394例,健康对照874例。选择6个snp,采用多重PCR结合高通量测序进行基因分型。通过通用多因素降维(GMDR)方法测试相互作用。结果:IL-23内rs3212227等位基因C和组合基因型AC+CC与GD与甲状腺肿显著相关(p分别为0.003和0.014)。IL-17RA内rs4819554等位基因G和组合基因型AG+GG与HT家族史和HT严重程度显著相关(p=0.011和0.027;P =0.041和0.035)。IL-17F中rs9463772的等位基因T和基因型CT+TT与HT的严重程度显著相关(p分别为0.001和0.027)。此外,GMDR分析在AITD、GD和HT患者中发现了高维基因-性别相互作用(il - 23r - il -23- il - 17ra - il - 17f -性别)。结论:本研究发现了新的AITD基因座和基因-性别相互作用。这一证据从另一个角度提示,性别、IL-23/IL-17通路和Th17细胞在AITD的发病机制中发挥重要作用。
{"title":"Association Between Polymorphisms of IL-23/IL-17 Pathway and Clinical Phenotypes of Autoimmune Thyroid Diseases.","authors":"Tiantian Cai, Guofei Wang, Yanping Yang, Kaida Mu, Jing Zhang, Yanfei Jiang, Jin-An Zhang","doi":"10.22034/iji.2022.93744.2255","DOIUrl":"https://doi.org/10.22034/iji.2022.93744.2255","url":null,"abstract":"<p><strong>Background: </strong>Several autoimmune and inflammatory disorders, including autoimmune thyroid diseases (AITD), have been linked to Th17 cells and the IL-23/IL-17 axis. Current data suggest that genetic variation contributes greatly to disease susceptibility to AITD.</p><p><strong>Objectives: </strong>To study the role of single nucleotide polymorphisms (SNPs) of IL-23/IL-17 pathway in AITD predisposition and test the gene-gene/gene-sex interactions in these loci.</p><p><strong>Methods: </strong>A total of 1051 patients with AITD, including 657 patients with Graves' disease (GD) and 394 patients with Hashimoto's thyroiditis (HT), and 874 healthy controls were enrolled in this case-control association study. Six SNPs were selected and genotyped by multiplex PCR combined with high-throughput sequencing. Interactions were tested by the general multifactor dimensionality reduction (GMDR) method.</p><p><strong>Results: </strong>Allele C and combinational genotype AC+CC of rs3212227 within IL-23 were significantly associated with GD with goiter (p=0.003 and 0.014, respectively). Allele G and combinational genotype AG+GG of rs4819554 within IL-17RA were significantly related to HT with family history and the severity of HT (p=0.011 and 0.027; p=0.041 and 0.035). Also, allele T and genotype CT+TT of rs9463772 within IL-17F were significantly correlated with the severity of HT (p=0.001 and 0.027, respectively). Moreover, high dimensional gene-sex interaction (IL-23R-IL-23-IL-17RA-IL-17F-sex) was identified in AITD, GD, and HT patients with GMDR analysis.</p><p><strong>Conclusions: </strong>Our study identified the novel loci and gene-sex interaction in AITD. This evidence, from another perspective, suggests that sex, IL-23/IL-17 pathway, and Th17 cells play an important role in the pathogenesis of AITD.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":null,"pages":null},"PeriodicalIF":0.9,"publicationDate":"2022-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40409204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}