Miao Zhu, Jun Zhang, Qingqing Shi, Xing Sun, Haibo Wang, Mei Sun, Yanqing Liu
{"title":"Rescue of HLH with T and B Lymphocyte Involvement Due to Epstein-Barr Virus by PD-1 Inhibitor/Ruxolitinib and Rituximab Combination Regimens: A Case Report.","authors":"Miao Zhu, Jun Zhang, Qingqing Shi, Xing Sun, Haibo Wang, Mei Sun, Yanqing Liu","doi":"10.22034/iji.2023.99254.2629","DOIUrl":"10.22034/iji.2023.99254.2629","url":null,"abstract":"<p><p>Hemophagocytic lymphohistiocytosis (HLH) is a fatal clinical syndrome. The most common cause of secondary HLH is Epstein-Barr virus (EBV) infection. EBV-HLH is a common clinical disease with high mortality, easy relapse, and poor prognosis. Therefore, treating EBV-HLH with T and B lymphocyte involvement is challenging, and selecting an appropriate treatment regimen is critical. Moreover, research on how to evaluate the recurrence index after remission is scarce. In this study, we reported a case of EBV-HLH successfully treated with programmed cell death protein-1 (PD-1) inhibitor in combination with rituximab. The regimen had a good curative effect, and we successfully detected the trend of early recurrence. Our findings indicated that PD-1 inhibitor in combination with rituximab may help to treat EBV-HLH and maintain EBV-infected T and B whole-line lymphocytes.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 4","pages":"466-472"},"PeriodicalIF":0.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49694121","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}
{"title":"Human Umbilical Cord Mesenchymal Stem Cells and their Extracellular Vesicles Modulate Pro- and Anti-inflammatory Cytokines in Ligature-induced Periodontitis.","authors":"Xixi Wang","doi":"10.22034/iji.2023.100211.2683","DOIUrl":"10.22034/iji.2023.100211.2683","url":null,"abstract":"<p><strong>Background: </strong>Periodontitis is a chronic inflammatory condition that affects the tissues supporting the teeth, ultimately leading to tooth loss. Mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) play a crucial role in periodontitis by modulating the activities of gum cells and the immune system.</p><p><strong>Objective: </strong>To investigate the therapeutic potential of human umbilical cord mesenchymal stem cells (hUCSCs) and EVs in regulating the inflammatory response associated with periodontitis.</p><p><strong>Methods: </strong>hUCSCs were isolated, subjected to flow cytometry analysis of surface markers, and differentiated into adipocyte and osteocyte. hUCSC-EVs were isolated and characterized using flow cytometry and electron microscopy. A periodontitis animal model was established in 30 female C57Bl/6 mice. Experimental groups received hUCSCs or hUCSCs-EVs, or vehicles intravenously. Animals were monitored for 4 weeks, and the periodontal tissues were used to assess the effects of hUCSCs and hUCSCs-EVs on the expression of pro- (TNF-α, IFN-γ, and IL-17a) and anti-inflammatory cytokines (TGF-β, IL-10, and IL-4). The secretion of these cytokines by splenocytes was also evaluated using ELISA.</p><p><strong>Results: </strong>The levels of IL-17a, IFN-γ, and TNFα significantly reduced, while TGF-β and IL-10 significantly increased in the periodontal tissues of the hUCSC and hUCSCEVs-treated mice. The expression of TNF-α, IFN-γ, and IL-17a significantly decreased, while the production of IL-10 and TGF-β significantly increased in splenocytes from the hUCSC and EVs-treated mice.</p><p><strong>Conclusion: </strong>hUCSCs and their EVs have the potential to attenuate the inflammatory response associated with periodontitis, possibly by downregulating pro-inflammatory cytokines and upregulating anti-inflammatory ones.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 4","pages":"446-455"},"PeriodicalIF":0.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813413","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}
Maryam Mohammadi, Hossein Asgarian-Omran, Behnam Najafi, Ahmad Najafi, Reza Valadan, Hossein Karami, Mohammad Naderisoraki, Maryam Alizadeforoutan, Ramin Shekarriz, Mohsen Tehrani
{"title":"Evaluation of mRNA Expressions of TOX and NR4As in CD8+ T cells in Acute Leukemia.","authors":"Maryam Mohammadi, Hossein Asgarian-Omran, Behnam Najafi, Ahmad Najafi, Reza Valadan, Hossein Karami, Mohammad Naderisoraki, Maryam Alizadeforoutan, Ramin Shekarriz, Mohsen Tehrani","doi":"10.22034/iji.2023.97902.2537","DOIUrl":"10.22034/iji.2023.97902.2537","url":null,"abstract":"<p><strong>Background: </strong>Thymocyte selection-associated high mobility group box protein (TOX) and members of the nuclear receptor 4A (NR4A) are known as transcription factors involved in T cell exhaustion.</p><p><strong>Objective: </strong>To evaluate the mRNA expression of TOX and NR4A1-3 in CD8+ T cells in acute leukemia.</p><p><strong>Methods: </strong>Blood samples were obtained from 21 ALL and 6 AML patients as well as 20 control subjects. CD8+ T cells were isolated using MACS. Relative gene expression of TOX and NR4A1-3 was then evaluated using qRT-PCR.</p><p><strong>Results: </strong>Comparison of mRNA expression of TOX in CD8+ T cells showed no significant difference among the study groups (p>0.05), while the expression of NR4A1 was significantly lower in AML patients than in the control group (p=0.0006). Also, the expression of NR4A2 and NR4A3 was significantly lower in both ALL (p=0.0049 and p=0.0005, respectively) and AML (p=0.0019 and p=0.0055, respectively) patients.</p><p><strong>Conclusion: </strong>NR4As expressions were found to be lower in CD8+ T cells from patients with AML and ALL compared to controls, whereas the mRNA expression of TOX showed no significant difference. Although TOX and NR4As are associated with CD8+ T cell exhaustion in solid tumors, they might play different roles in acute leukemia, which requires further investigation.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 4","pages":"438-445"},"PeriodicalIF":0.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"92157381","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}
Maryam Asadi, Razie Kiani, Vahid Razban, Seyed Nooreddin Faraji, Amirhossein Ahmadi, Jafar Fallahi, Amin Ramezani, Nasrollah Erfani
{"title":"Harnessing the Power of CAR-NK Cells: A Promising Off-the-Shelf Therapeutic Strategy for CD38-Positive Malignancies.","authors":"Maryam Asadi, Razie Kiani, Vahid Razban, Seyed Nooreddin Faraji, Amirhossein Ahmadi, Jafar Fallahi, Amin Ramezani, Nasrollah Erfani","doi":"10.22034/iji.2023.100424.2691","DOIUrl":"10.22034/iji.2023.100424.2691","url":null,"abstract":"<p><strong>Background: </strong>CD38 is highly expressed on multiple myeloma (MM) cells and has been successfully targeted by different target therapy methods. This molecule is a critical prognostic marker in both diffuse large B-cell lymphoma and chronic lymphocytic leukemia.</p><p><strong>Objective: </strong>We have designed and generated an anti-CD38 CAR-NK cell applying NK 92 cell line. The approach has potential application as an off-the-shelf strategy for treatment of CD38 positive malignancies.</p><p><strong>Methods: </strong>A second generation of anti-CD38 CAR-NK cell was designed and generated, and their efficacy against CD38-positive cell lines was assessed in vitro. The PE-Annexin V and 7-AAD methods were used to determine the percentage of apoptotic target cells. Flow cytometry was used to measure IFN-γ, Perforin, and Granzyme-B production following intracellular staining. Using in silico analyses, the binding capacity and interaction interface were evaluated.</p><p><strong>Results: </strong>Using Lentivirus, cells were transduced with anti-CD38 construct and were expanded. The expression of anti-CD38 CAR on the surface of NK 92 cells was approximately 25%. As we expected from in silico analysis, our designed CD38-chimeric antigen receptor was bound appropriately to the CD38 protein. NK 92 cells that transduced with the CD38 chimeric antigen receptor, generated significantly more IFN-γ, perforin, and granzyme than Mock cells, and successfully lysed Daudi and Jurkat malignant cells in a CD38-dependent manner.</p><p><strong>Conclusion: </strong>The in vitro findings indicated that the anti-CD38 CAR-NK cells have the potential to be used as an off-the-shelf therapeutic strategy against CD38-positive malignancies. It is recommended that the present engineered NK cells undergo additional preclinical investigations before they can be considered for subsequent clinical trial studies.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 4","pages":"410-426"},"PeriodicalIF":0.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813475","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}
{"title":"Relationship between TIM3 Expression on Peripheral T Lymphocytes and Post-Stroke Depression.","authors":"Qifen Mao, Peng Zhang, Weicui Qi, Yueping Xia, Tingting Chen, Xiaofang Li, Songquan Xu, Zhiqiang Zhong, Zuifei Shangguan","doi":"10.22034/iji.2023.98917.2598","DOIUrl":"10.22034/iji.2023.98917.2598","url":null,"abstract":"<p><strong>Background: </strong>T cell immunoglobulin and mucin domain-containing protein 3 (TIM3) is a regulatory molecule expressed on a variety of cell types, including CD3+ T cells. Few studies have been conducted to look into the correlation between TIM3 expression on peripheral T lymphocytes and post-stroke depression (PSD).</p><p><strong>Objective: </strong>To investigate the relationship between TIM3 expressions on peripheral T lymphocytes in PSD patients.</p><p><strong>Methods: </strong>Acute stroke patients without depression (NPSD) (n=65), PSD patients (n=23), and body mass index (BMI), age, and education-matched healthy controls (HC) (n=59) were enrolled. Using flow cytometry, TIM3 expression was examined in the peripheral CD3+ CD4+ and CD3+ CD8+ T lymphocytes. Evaluation of the depressive severity in PSD patients was assessed using a 17-item Hamilton Depression Rating Scale (HAM-D-17). We used enzyme-linked immunosorbent assay (ELISA) to determine the serum concentrations of IL-1β, IL-6, IL-10, and IL-18. We further assessed the relationships between TIM3 expression, serum cytokine levels, and the HAM-D-17 scores.</p><p><strong>Results: </strong>CD3+ CD4+ T cells reduced significantly in PSD patients compared with the NPSD patients and HC. Both NPSD patients and PSD patients had a significant increase in TIM3 expression in their peripheral CD3+ CD4+ T lymphocytes, compared with HC. In PSD patients, a higher frequency of peripheral CD3+ CD8+ T lymphocytes showed significant expression of TIM3 compared to NPSD patients and HC. High TIM3 level on peripheral CD3+ CD8+ T lymphocytes was positively associated with the HAM-D score.</p><p><strong>Conclusion: </strong>Patients with PSD exhibit immune dysfunction. TIM3 might contribute to the development and severity of PSD, making it a potential therapeutic target.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 4","pages":"427-437"},"PeriodicalIF":0.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138813415","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}
{"title":"Antibody Production after COVID-19 Vaccination in Patients with Inborn Errors of Immunity.","authors":"Maryam Nourizadeh, Elham Feizabadi, Milad Mirmoghtadaei, Ashraf Mohammadi, Mohammad Reza Fazlollahi, Leila Moradi, Zahra Pourpak","doi":"10.22034/iji.2023.97759.2525","DOIUrl":"10.22034/iji.2023.97759.2525","url":null,"abstract":"<p><strong>Background: </strong>Few studies have evaluated COVID-19 vaccine efficacy in patients with inborn errors of immunity (IEI).</p><p><strong>Objective: </strong>To evaluate the levels of antibody (Ab) production and function after COVID-19 vaccination in IEI patients with phagocytic, complement, and Ab deficiencies and their comparison with healthy controls.</p><p><strong>Methods: </strong>Serum samples were collected from 41 patients and 32 healthy controls at least one month after the second dose of vaccination, while clinical evaluations continued until the end of the third dose. Levels of specific anti-receptor-binding domain (RBD) IgG and anti-RBD neutralizing antibodies were measured using EUROIMMUN and ChemoBind kits, respectively. Conventional SARS-CoV-2 neutralization test (cVNT) was also performed. Cutoff values of ≤20, 20-80, and ≥80 (for cVNT and Chemobined) and 0.8-4.2, 4.2-8.5, and ≥8.5 (for EUROIMMUN) were defined as negative/weak, positive/moderate, and positive/significant, respectively.</p><p><strong>Results: </strong>A considerable distinction was observed between the Ab-deficient patients and the controls for Ab concentration (EUROIMMUN, p<0.01) and neutralization (ChemoBind, p<0.001). However, there was no significant difference compared with the other patient groups. A near-zero cVNT in Ab-deficient patients was found compared to the controls (p<0.01). A significant correlation between the two kits was found using the whole data (R2=0.82, p<0.0001).</p><p><strong>Conclusion: </strong>Despite varying degrees of Ab production, all Ab deficient patients, as well as almost half of those with complement and phagocytic defects, did not effectively neutralize the virus (cVNT). In light of the decreased production and efficiency of the vaccine, a revised immunization plan may be needed in IEI.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 4","pages":"400-409"},"PeriodicalIF":0.9,"publicationDate":"2023-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49685192","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}
{"title":"SPIB Knockdown Inhibits the Immune Escape of Ovarian Cancer Cells by Reducing PD-L1 (CD274) Expression and Inactivating the JAK/STAT Pathway.","authors":"Wenfei Gu, GuangTao Qi, Li Chen","doi":"10.22034/iji.2023.98236.2559","DOIUrl":"https://doi.org/10.22034/iji.2023.98236.2559","url":null,"abstract":"<p><strong>Background: </strong>Spi-B transcription factor (SPIB) is an E-twenty-six (ETS) transcription factor associated with tumor immunity.</p><p><strong>Objective: </strong>To investigate the functions and mechanisms of SPIB in ovarian cancer (OC) cells.</p><p><strong>Methods: </strong>Cell proliferation, apoptosis, migration, and invasion were determined using colony formation, EdU, flow cytometry, and transwell assays, respectively. The binding sites of programmed death-ligand 1 (PD-L1) and SPIB were predicted using the JASPAR database and verified using the ChIP and luciferase reporter assays.</p><p><strong>Results: </strong>SPIB knockdown inhibited OC cell proliferation, migration, and invasion, and significantly boosted apoptosis (p<0.05). SPIB directly enhanced PD-L1 transcription in OVCAR-3 and SKOV3 cells (p<0.05). Importantly, the JAK/STAT pathway was markedly inactivated in OC cells upon SPIB knockdown. SPIB knockdown markedly decreased JAK2 and STAT1 phosphorylation in OVCAR-3 and SKOV3 cells (p<0.05).</p><p><strong>Conclusion: </strong>These data indicate that SPIB knockdown inhibits OC cell progression by downregulating PD-L1 and inactivating the JAK/STAT pathway.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 3","pages":"335-347"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10530729","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}
{"title":"Effects of Blocking NLRP3 Inflammasome on Type II Innate Lymphoid Cell Response in Allergic Rhinitis.","authors":"Guoqing Gong, Peng Huang, Changliang Yang, Chengcheng Huang, Zhao Zhang, Ruiyao Chen, Tingfeng Sun, Guang Yang","doi":"10.22034/iji.2023.96966.2473","DOIUrl":"10.22034/iji.2023.96966.2473","url":null,"abstract":"<p><strong>Background: </strong>Type 2 innate lymphoid cells (ILC2s) and NLRP3 inflammasome are related to allergic and inflammatory responses. NLRP3 inflammasome inhibitor MCC950 was demonstrated to ameliorate allergic rhinitis (AR) in animal models.</p><p><strong>Objective: </strong>To elucidate the effect of MCC950 on ILC2 responses in AR.</p><p><strong>Methods: </strong>NLRP3 inflammasome, ILC2s, IL-5+ILC2s, IL-13+ILC2s, and Th2-related factors were examined in 30 AR patients. ILC2s were identified as Lin-CRTH2+CD127+lymphocytes. ILC2s isolated from PBMCs were stimulated with LPS plus ATP. The effect of MCC950, IL-1β, and IL-18 on ILC2 responses was detected by flow cytometry. AR models were established in 60 BALB/c mice. Nasal symptoms and ILC2 responses in the AR models after MCC950 treatment were detected. Human nasal epithelial cells were stimulated with IL-13 (10 ng/mL) and treated with MCC950 (10 μM).</p><p><strong>Results: </strong>AR patients showed activated NLRP3 inflammasome and increased ILC2 responses compared to controls. NLRP3 inflammasome levels in the AR patients were positively related to the proportion of ILC2s, IL-5+ILC2s, and IL-13+ILC2s in total PBMCs. MCC950 treatment or IL-1β/IL-18 suppression inhibited ILC2 proliferation and Th2-related factors (GATA3, RORα, IL-5, and IL-13). MCC950 administration alleviated frequencies of nasal rubbing and sneezes in the AR models. ILC2s, IL-5+ILC2s, and IL-13+ILC2s in mice were reduced by MCC950. MCC950 inhibited NLRP3 inflammasome in the in vitro models of AR.</p><p><strong>Conclusion: </strong>MCC950 inhibited ILC2 responses in AR and mice models, suggesting that blocking NLRP3 inflammasome may be a promising target for AR clinical treatment.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"3 20","pages":"287-302"},"PeriodicalIF":1.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10134609","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}
Alireza Fereidouni, Hamidreza Safari, Hadis Rezapoor, Sara Mahmoudzadeh, Mohammad Fereidouni
{"title":"Evaluation of SARS-CoV-2 Specific Antibodies in Recovered Patients by Different ELISA Kits.","authors":"Alireza Fereidouni, Hamidreza Safari, Hadis Rezapoor, Sara Mahmoudzadeh, Mohammad Fereidouni","doi":"10.22034/iji.2023.93206.2202","DOIUrl":"https://doi.org/10.22034/iji.2023.93206.2202","url":null,"abstract":"<p><strong>Background: </strong>The coronavirus disease 2019 (COVID-19) was first reported in December 2019 in Wuhan, Hubei Province of China. As long as the 27th of December 2021, approximately 280 million people have been infected with coronavirus, resulting in more than 5,418,421 deaths worldwide. Since the beginning of the COVID-19 pandemic, different methods were introduced for diagnosing coronavirus-infected patients and evaluating the immune response, following the vaccination.</p><p><strong>Objective: </strong>The current study aimed to compare the level of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) specific IgG in a group of patients who recovered from COVID-19, measured by three different enzyme-linked immunosorbent assay (ELISA) kits.</p><p><strong>Methods: </strong>This cross-sectional study was conducted on sera from patients who recovered from a real-time reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed COVID-19 in Birjand, South Khorasan, Iran. SARS-CoV-2 anti-nucleocapsid (N) and spike (S) protein IgG levels were measured using commercial ELISA kits. Comparison between groups was made using one-way ANOVA and Tukey post hoc tests.</p><p><strong>Results: </strong>The mean titer of anti-N IgG was significantly higher for the PishtazTeb Diagnostics kit than the Ideal Tashkhis Atieh kit (p<0.05). There was no correlation between the titer of anti-N IgG (PishtazTeb Diagnostics and Ideal Tashkhis Atieh) and anti-S IgG (Chemobind Company) antibodies.</p><p><strong>Conclusion: </strong>This study indicates that the domestic ELISA kits have variable but acceptable sensitivity for detecting SARS-CoV-2 specific IgG antibodies.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 3","pages":"374-381"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198886","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}
{"title":"Implications of Complement Imbalance in COVID-19: A Molecular Mechanistic Discussion on the Importance of Complement Balance.","authors":"Mehdi Torabizadeh, Helia Modaresi Asfeh, Zeinab Deris Zayeri, Cerdan Dominique, Hashem Kazemi, Najmaldin Saki","doi":"10.22034/iji.2023.97585.2522","DOIUrl":"10.22034/iji.2023.97585.2522","url":null,"abstract":"<p><p>Two central questions in COVID-19 treatment which should be considered are: \"How does the imbalance of the complement system affect the therapeutic approaches?\" and \"Do we consider complement inhibitors in therapeutic protocols?\". The complement system is a double-edged sword since it may either promote immune responses against COVID-19 or contribute to destructive inflammation in the host. Therefore, it is crucial to regulate this system with complement inhibitors. In this manuscript, we discuss the molecular mechanisms of complement and complement inhibitors in COVID-19 patients. We searched the terms \"COVID-19\", \"Complement\", \"Complement inhibitor\", \"SARS-CoV-2\", and all complement fragments and inhibitors from 2000 to 2022 in PubMed and google scholar and checked the pathways in \"KEGG pathway database\". Complement is not well-appreciated in the treatment protocols despite its multiple roles in the disease, and most of the preventive anti-inflammatory therapeutic approaches did not include a complement inhibitor in COVID-19 therapeutic protocols. In this review article, we discussed the most recent studies regarding complement components mediated interventions and the mechanism of these interventions in COVID-19 patients. Since the control of the complement system overactivation is associated with a better prognosis in the initial stages of COVID-19, heparin, anti-thrombin, C1-inhibitor, montelukast, and hydralazine can be effective in the initial stages of this viral infection. Recombinant complement activation (RCA) proteins are more effective in regulating complement compared to terminal pathway therapeutic approaches such as the C3a and C5a inhibitors.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"3 20","pages":"247-261"},"PeriodicalIF":1.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10516300","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}