Iranian Journal of Immunology最新文献

{"title":"Synthesized Anti-HER2 Trastuzumab-MCC-DM1 Conjugate: An Evaluation of Efficacy and Cytotoxicity.","authors":"Soodabeh Shafiee,&nbsp;Roya Mirzaei,&nbsp;Malihe Salehi,&nbsp;Neda Jalili,&nbsp;Amir Taheri,&nbsp;Leila Farahmand","doi":"10.22034/iji.2023.96229.2420","DOIUrl":"https://doi.org/10.22034/iji.2023.96229.2420","url":null,"abstract":"<p><strong>Background: </strong>Trastuzumab is a humanized monoclonal antibody that targets site-specifically human epidermal growth factor-2 receptor (HER2) cell surface antigen overexpressed in approximately 20% of human breast carcinomas. Despite its positive therapeutic outcomes, a large proportion of individuals are unresponsive to the treatment with the trastuzumab or develop resistance to it.</p><p><strong>Objective: </strong>To evaluate a chemically synthesized trastuzumab-based antibody-drug conjugate (ADC) to improve the trastuzumab therapeutic index.</p><p><strong>Methods: </strong>The current study explored the physiochemical characteristics of the trastuzumab conjugated to a cytotoxic chemotherapy agent DM1 via Succinimidyl 4-(N-maleimidomethyl) cyclohexane-1-carboxylate (SMCC) linker, created in our earlier study, using SDS-PAGE, UV/VIS, and RP-HPLC analyses. The antitumor effects of the ADCs were analyzed using MDA-MB-231 (HER2-negative) and SK-BR-3 (HER2-positive) cell lines utilizing in vitro cytotoxicity, viability, and binding assays. Three different formats of a HER2-targeting agent: trastuzumab, synthesized trastuzumab-MCC-DM1, and commercially available drug T-DM1 (Kadcyla®) were compared.</p><p><strong>Results: </strong>UV-VIS spectroscopic analysis showed that the trastuzumab-MCC-DM1 conjugates, on average, entailed 2.9 DM1 payloads per trastuzumab. A free drug level of 2.5% was determined by RP-HPLC. The conjugate appeared as two bands on a reducing SDS-PAGE gel. MTT viability assay showed that conjugating trastuzumab with DM1 significantly improved the antiproliferative effects of this antibody in vitro. Importantly, the evaluations using LDH release and cell apoptosis assays confirmed that trastuzumab maintains its ability to induce cell death response while conjugating with the DM1. The binding efficiency of trastuzumab-MCC-DM1 was comparable to that of the naked trastuzumab.</p><p><strong>Conclusion: </strong>Trastuzumab-MCC-DM1 was found effective against HER2+ tumors. The potency of this synthesized conjugate brings it closer to the commercially available T-DM1.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 3","pages":"303-315"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10548199","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":"Impact of Echinococcus granulosus Antigens on Monocyte Development and Dendritic Cell Differentiation.","authors":"Mingxia Wang,&nbsp;Fei Qiao,&nbsp;Zihua Li,&nbsp;Qiang Wang,&nbsp;Zailing Shang,&nbsp;Junhu Hei,&nbsp;Xuelin Ma,&nbsp;Yana Wang","doi":"10.22034/iji.2023.98163.2557","DOIUrl":"https://doi.org/10.22034/iji.2023.98163.2557","url":null,"abstract":"<p><strong>Background: </strong>Different subtypes of dendritic cells (DCs) can induce different types of immune responses. Our previous study found that Echinococcus granulosus (E. granulosus) antigens (Eg.ferritin, Eg.mMDH and Eg.10) stimulated DC differentiation to different subtypes and produced different immune responses.</p><p><strong>Objective: </strong>To further understand whether Eg.ferritin, Eg.mMDH and Eg.10 affect the DC-mediated immune response by promoting the differentiation of monocytes to DCs.</p><p><strong>Methods: </strong>Bone marrow-derived monocytes were exposed to three antigens of E. granulosus on days 0, 3, 5, and 7. The percentage of monocyte-derived DCs (moDCs), DCs subsets, and the expression of surface molecules of DCs at different time points in different groups were assessed by flow cytometry. The levels of cytokines of IL-1β, IL-4, IL-6, IL-10, IL-13, IFN-γ, TNF-α, IL-12p70, IL-18, IL-23, and IL-27 in the cell culture supernatant were detected by multi-factorial detection technology.</p><p><strong>Results: </strong>The percentage of moDCs revealed that none of the three antigens blocked monocyte differentiation to DCs. The monocytes of 7-day-old cultures showed increased sensitivity to these antigens. The Eg.ferritin induced more mature DCs, which expressed high levels of MHC II and costimulatory molecules, and secreted Th1 cytokines. Eg10 and Eg.mMDH induced lower degrees of DC maturation, however differentiated DCs were in a semi-mature state due to low expression of MHC II and costimulatory molecules and secretion of higher Th2 and lower Th1 cytokines.</p><p><strong>Conclusion: </strong>Eg.ferritin promotes full maturation of DCs and induces Th1 immune response, whereas Eg.10 and Eg.mMDH induce semi-mature DCs producing higher levels of Th2 cytokines.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 3","pages":"348-358"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10198921","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":"Angiopoietin-like 4 (ANGPTL4) Suppression Ameliorates Lupus Nephritis in MRL/lpr Mice by Inactivating NLRP3 Inflammasome and Inhibiting Inflammatory Response.","authors":"Dan Luo, Jun Li, Manli Hu, You Wang, Pei Pi, Min Ning, Jun Wu","doi":"10.22034/iji.2023.97942.2541","DOIUrl":"10.22034/iji.2023.97942.2541","url":null,"abstract":"<p><strong>Background: </strong>Lupus nephritis (LN) refers to the injury caused by systemic lupus erythematosus (SLE) involving the kidneys. A previous study identified angiopoietin-like protein 4 (ANGPTL4) as a novel urinary biomarker for tracking disease activity in LN.</p><p><strong>Objective: </strong>To investigate the detailed role and regulatory mechanism of ANGPTL4 in experimental models of LN.</p><p><strong>Methods: </strong>MRL/lpr mice 11-week-old were injected with adeno-associated virus (AAV)-mediated ANGPTL4 short hairpin RNA (shRNA). At 16 and 20 weeks of age, 24-h urine samples were harvested to measure proteinuria levels. After the mice were sacrificed, blood and kidney tissues were harvested to examine serum creatinine (cr) and blood urea nitrogen (BUN) levels, kidney histological changes, and pro-inflammatory cytokine production. Additionally, the levels of NLRP3 inflammasome-associated molecules in mouse renal tissues were detected to clarify the underlying mechanism.</p><p><strong>Results: </strong>The AAV-sh-ANGPTL4 injection significantly reduced the proteinuria, cr, and BUN levels in MRL/lpr mice. ANGPTL4 silencing ameliorated glomerular, tubular, and interstitial damage in mice, mitigating the pathological alternations of LN. In addition, ANGPTL4 knockdown repressed pro-inflammatory cytokine production in the kidneys. Mechanically, ANGPTL4 suppression inhibited NLRP3 inflammasome expression in renal tissues of mice.</p><p><strong>Conclusion: </strong>ANGPTL4 silencing inhibits the NLRP3 inflammasome-mediated inflammatory response, thereby ameliorating LN in MRL/lpr mice.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"3 20","pages":"316-326"},"PeriodicalIF":1.1,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139436","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":"CD39 Expression in Peripheral T Cells is Associated with Clinicopathological Characteristics in Patients with Cervical Cancer.","authors":"Kuo Zhao,&nbsp;Dongmei Han,&nbsp;Lu Tang,&nbsp;Hao Jin","doi":"10.22034/iji.2023.97037.2527","DOIUrl":"https://doi.org/10.22034/iji.2023.97037.2527","url":null,"abstract":"<p><strong>Background: </strong>CD39 is an inhibitory checkpoint exerting rate-limiting effects on the ATP-adenosine pathway. It can be targeted to block adenosine-mediated immunosuppression.</p><p><strong>Objective: </strong>To analyze the relationship between the CD39 expression and clinicopathological characteristics including FIGO stage, lymph node and distant metastasis, and to further explore its potential role in cervical cancer.</p><p><strong>Methods: </strong>Peripheral blood was collected from 59 healthy people and 43 patients with cervical cancer. The percentage and absolute counts of CD3-positive, CD4-positive and CD8-positive T lymphocytes, CD4/CD8 ratio and the percentage of the CD39+ T cells in T lymphocytes were assessed by flow cytometry, and their correlations with clinical parameters were analyzed.</p><p><strong>Results: </strong>Absolute numbers of CD8+ T lymphocytes, CD4/CD8 ratios, and the percentage of the CD39+ T cells were linked with FIGO stage, lymph node metastasis, and distant metastasis. The total numbers of CD8+ T lymphocytes were significantly higher in the peripheral blood of patients with cervical cancer in the early and middle stages than in the advanced stage. In addition, patients with early and middle-stage cervical cancer had considerably lower percentage of CD4+ CD39 + and CD8 + CD39 + T lymphocytes than those with advanced cervical cancer.</p><p><strong>Conclusion: </strong>These results suggest that the absolute counts of CD8+ T lymphocytes may be associated with the patient's prognosis and that the CD39 molecule, expressed on the surface of CD8+ T cells, is also related to FIGO stage, lymph node metastasis, and distant metastasis. CD39 expression on CD8-positive T cells exhibits a negative correlation with the number of CD8-positive T lymphocytes.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 3","pages":"276-286"},"PeriodicalIF":0.9,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10139420","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":"Selective IgA Deficiency with Multiple Autoimmune Comorbidities: A Case Report and Literature Review.","authors":"Liang Hua,&nbsp;Dongjie Guo,&nbsp;Xin Liu,&nbsp;Jiaqi Jiang,&nbsp;Qian Wang,&nbsp;Yi Wang,&nbsp;Te Liu,&nbsp;Fulun Li","doi":"10.22034/iji.2023.97452.2513","DOIUrl":"https://doi.org/10.22034/iji.2023.97452.2513","url":null,"abstract":"<p><strong>Case: </strong>Individuals with Selective Immunoglobulin-A Deficiency (SIgAD) are often asymptomatic, and symptomatic SIgAD patients often have autoimmune comorbidities. A 48-year-old Han Chinese man presented with abdominal discomfort, hematochezia, and a large tumor in the anogenital region. The primary diagnosis of SIgAD was based on the patient's age, serum IgA concentration (0.067 g/L), and the evidence of chronic respiratory infection. No other immunoglobulin deficiency or evidence of immunosuppression was present. The primary diagnosis of giant condyloma acuminatum was based on human papilloma virus-6-positive laboratory results and histological characteristics. The tumor and adjacent skin lesions were resected. Hemoglobin concentration fell to 5.50 g/dL, and an emergency erythrocyte transfusion was performed. The body temperature increased to 39.8 ºC, suggesting a transfusion reaction, and 5 mg dexamethasone was administered intravenously. Hemoglobin concentration stabilized at 10.5 g/dL. The clinical signs and laboratory results indicated autoimmune hemolytic anemia, systemic lupus erythematosus, and Hashimoto's thyroiditis. Abdominal discomfort and hematochezia subsided. Though uncommon, the manifestation of multiple autoimmune comorbidities can occur in SIgAD patients. Further research is needed regarding the causes of SIgAD and the autoimmune disorders that often occur as comorbidities.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 2","pages":"232-239"},"PeriodicalIF":0.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9906462","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":"The Anti-inflammatory Effect of Ginger Extract on the Animal Model of Multiple Sclerosis.","authors":"Fatemeh Kamankesh,&nbsp;Ali Ganji,&nbsp;Ali Ghazavi,&nbsp;Ghasem Mosayebi","doi":"10.22034/iji.2023.97156.2482","DOIUrl":"https://doi.org/10.22034/iji.2023.97156.2482","url":null,"abstract":"<p><strong>Background: </strong>Experimental autoimmune encephalomyelitis (EAE), as an autoimmune disease in the central nervous system (CNS), is an animal model for multiple sclerosis (MS) mediated by T lymphocytes.</p><p><strong>Objective: </strong>To investigate ginger extract's effect on reducing inflammation and improving the symptoms in the EAE model.</p><p><strong>Methods: </strong>The EAE was induced by injecting MOG35-55 and pertussis toxin into eight-week-old female C57BL6 mice. The mice were treated with an intraperitoneal injection of 300 mg/kg/day of hydroalcoholic extract of ginger for 21 days. The disease severity and weight changes were measured daily. Then, the mice spleens were removed; the gene expressions of interleukin (IL)-17, transforming growth factor beta (TGF-β), interferon-γ (IFN-γ), and tumor necrosis factor α (TNF-α) were analyzed by Real-time PCR and the percentage of regulatory T lymphocytes (Treg cells) was determined by flow cytometry. Serum nitric oxide and antioxidant capacity were measured, and brain tissue sections were prepared to investigate the leukocyte infiltration and plaque formation.</p><p><strong>Results: </strong>The severity of symptoms in the intervention group was lower than in the control. The gene expression levels of inflammatory cytokines, including IL-17 (P=0.04) and IFN-γ (P=0.01), were reduced. The Treg cells increased significantly, and the serum nitric oxide level was lower in the ginger-treated group. There was no significant difference in lymphocyte infiltration in the brain between the two groups.</p><p><strong>Conclusion: </strong>The present study indicated that ginger extract could effectively reduce inflammatory mediators and modulate immune responses in EAE.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 2","pages":"211-218"},"PeriodicalIF":0.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9907529","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":"The Upregulation of HLA-G1 and miRNA-34a in Lens Epithelial Cells of Diabetic Retinopathy Patients.","authors":"Elnaz Taghvaei-Bijandi,&nbsp;Fatemeh Abedian,&nbsp;Ahmad Ahmadzadeh Amiri,&nbsp;Narjes Jafari,&nbsp;Saeid Abediankenari","doi":"10.22034/iji.2023.97403.2510","DOIUrl":"https://doi.org/10.22034/iji.2023.97403.2510","url":null,"abstract":"<p><strong>Background: </strong>Retinopathy of diabetes is a chronic diabetes mellitus complication affecting retinal vessels, and some ocular complications' molecular mechanisms remain obscure.</p><p><strong>Objective: </strong>To evaluate the expression of HLA-G1, HLA-G5, miRNA-181a, and miRNA-34a in the lens epithelial cells of patients with retinopathy of diabetes.</p><p><strong>Methods: </strong>In a case-control study, 30 diabetic patients with retinopathy, 30 diabetic patients without retinopathy, and 30 cataract patients without diabetes mellitus as the control group were enrolled after a full description with details about the study methods and objectives. The expression of HLA G1, HLA G5, miRNA-181a, and miRNA-34a in lens epithelial cells was assessed by quantitative RT PCR. Moreover, the levels of HLA-G protein in aqueous humor were evaluated by the ELISA method.</p><p><strong>Results: </strong>HLA-G1 expression was significantly upregulated in the retinopathy group (P=0.003). The aqueous humor of diabetic retinopathy patients contained significantly higher levels of HLA-G protein compared with the non-diabetic patients (P=0.001). miRNA-181a was significantly downregulated in the diabetic retinopathy group compared with the patients without diabetes (P=0.001). In addition, miRNA-34a was upregulated in the retinopathy group (P=0.009).</p><p><strong>Conclusion: </strong>Taken together, the present results showed that HLA-G1 and miRNA-34a can be valuable markers for diabetic retinopathy. Our data offers new perspectives for improving the control of inflammation in the lens epithelial cells by considering HLA-G and miRNA.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 2","pages":"202-210"},"PeriodicalIF":0.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9555729","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":"LKB1 Positively Regulates Dendritic Cell-induced T Cell Immunity and Suppresses Tumor Development.","authors":"Wenjie Zhang,&nbsp;Shan Liu,&nbsp;Lin Zhao,&nbsp;Juncheng Wang,&nbsp;Meng Liu,&nbsp;Fengge Wang,&nbsp;Yuekang Xu","doi":"10.22034/iji.2023.96163.2412","DOIUrl":"https://doi.org/10.22034/iji.2023.96163.2412","url":null,"abstract":"<p><strong>Background: </strong>The functions of dendritic cells (DCs) are influenced by their intracellular metabolism, in which liver kinase B1 (LKB1) plays an important role. However, due to the difficulty in isolating the DCs, the roles of LKB1 in DC maturation and functions in tumor settings have been poorly characterized.</p><p><strong>Objective: </strong>To investigate the roles of LKB1 in DC functions including phagocytosis and presentation of antigens, activation, T cell differentiation, and ultimately tumor eradication.</p><p><strong>Methods: </strong>Genetic modification of Lkb1 in the DCs was made by lentiviral transduction, and their impacts on T cell proliferation, differentiation, activity, or B16 melanoma metastasis were examined by flow cytometry, qPCR, or lung tumor nodule counting.</p><p><strong>Results: </strong>LKB1 did not affect antigen uptake and presentation by the DCs, but facilitated the stimulation of T cell proliferation. Interestingly, following T cell activation, Foxp3-expressing regulatory T cells (Treg) were increased (P=0.0267) or decreased (P=0.0195) in mice injected with Lkb1 knockdown DCs or overexpressing DCs, respectively. Further exploration revealed that LKB1 inhibited OX40L (P=0.0385) and CD86 (P=0.0111) expression, and these co-stimulatory molecules enhanced Treg proliferation, and downregulated immune suppressive cytokine IL-10 (P=0.0315). Moreover, we found that the injection of the DCs with limited LKB1 expression before tumor inoculation could reduce their production of granzyme B (P<0.0001) and perforin (P=0.0042) from CD8+T cells, thereby impairing their cytotoxicity and promoting tumor growth.</p><p><strong>Conclusion: </strong>Our data suggest that LKB1 can enhance DC-mediated T cell immunity by restraining Treg development and thereby suppressing tumor growth.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 2","pages":"145-158"},"PeriodicalIF":0.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9556175","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":"Estrogen Receptor Alpha Gene (ESR1) Facilitates Th2-immune Response and Enhances Th2 Cytokines in Experimental Atopic Dermatitis Mice.","authors":"Jianrong Niu,&nbsp;Hui Zhou,&nbsp;Rong Tian,&nbsp;Xudong Wang","doi":"10.22034/iji.2023.97283.2494","DOIUrl":"https://doi.org/10.22034/iji.2023.97283.2494","url":null,"abstract":"<p><strong>Background: </strong>Molecular markers are involved in atopic dermatitis (AD) pathogenesis. The estrogen receptor (ESR)-1 gene, encoding ERα, is reported to express aberrantly in AD patients.</p><p><strong>Objective: </strong>To detect the biological functions of ESR1 in 2,4 dinitrochlorobenzene (DNCB)-treated mice.</p><p><strong>Methods: </strong>The DNCB-treated mice received a topical application of emulsion containing the 1,3-bis(4 hydroxyphenyl)-4-methyl-5-[4-(2-piperidinyl ethoxy) phenol]-1H-pyrazole dihydrochloride (MPP; an ESR1-selective antagonist) to dorsal skins and ears. Then the dermatitis scores, histopathological changes, and cytokine levels were evaluated.</p><p><strong>Results: </strong>MPP specifically downregulated ESR1 expression in DNCB-applied mice. Functionally, application of MPP abolished the DNCB-induced promotion in dermatitis score. Additionally, MPP administration protected against DNCB-induced dermatitis severity, suppressed mast cell infiltration and reduced production of immunoglobulin E (IgE) and thymus and activation-regulated chemokine (TARC). Moreover, MPP treatment inhibited DNCB-induced production of Th2 cytokines and infiltration of CD4+ T cells.</p><p><strong>Conclusion: </strong>ESR1 facilitates Th2-immune response and enhances Th2 cytokines in AD mice.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 2","pages":"167-176"},"PeriodicalIF":0.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9562815","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":"Novel Monoclonal Antibodies Specific for Human Ki67 and P53 Tumor Markers in Breast Cancer Tissue Samples.","authors":"Masoud Hassanzadeh Makoui,&nbsp;Maryam Mobini,&nbsp;Jalal Khoshnoodi,&nbsp;Tannaz Bahadori,&nbsp;Forough Golsaz-Shirazi,&nbsp;Hedieh Moradi Tabriz,&nbsp;Zahra Madjd,&nbsp;Mahmood Jeddi-Tehrani,&nbsp;Amir-Hassan Zarnani,&nbsp;Mohammad Mehdi Amiri,&nbsp;Fazel Shokri","doi":"10.22034/iji.2023.96926.2469","DOIUrl":"https://doi.org/10.22034/iji.2023.96926.2469","url":null,"abstract":"<p><strong>Background: </strong>Ki67 and P53 are important diagnostic and prognostic biomarkers expressed in several cancers. The current standard method for evaluating Ki67 and P53 in cancer tissues is immunohistochemistry (IHC), and having highly sensitive monoclonal antibodies against these biomarkers is necessary for an accurate diagnosis in the IHC test.</p><p><strong>Objective: </strong>To generate and characterize novel monoclonal antibodies (mAbs) against human Ki67 and P53 antigens for IHC purposes.</p><p><strong>Methods: </strong>Ki67 and P53-specific mAbs were produced by the hybridoma method and screened by enzyme-linked immunosorbent assay (ELISA) and IHC techniques. Selected mAbs were characterized using Western blot and flow cytometry, and their affinities and isotypes were determined by ELISA. Moreover, using the IHC technique in 200 breast cancer tissue samples, we assessed the specificity, sensitivity, and accuracy of the produced mAbs.</p><p><strong>Results: </strong>Two anti-Ki67 (2C2 and 2H1) and three anti-P53 mAbs (2A6, 2G4, and 1G10) showed strong reactivity to their target antigens in IHC. The selected mAbs were also able to recognize their targets by flow cytometry as well as Western blotting using human tumor cell lines expressing these antigens. The specificity, sensitivity, and accuracy calculated for clone 2H1 were 94.2%, 99.0%, and 96.6%, and for clone 2A6 were 97.3%, 98.1%, and 97.5%, respectively. Using these two monoclonal antibodies, we found a significant correlation between Ki67 and P53 overexpression and lymph node metastasis in patients with breast cancer.</p><p><strong>Conclusion: </strong>The present study showed that the novel anti-Ki67 and anti-P53 mAbs could recognize their respective antigens with high specificity and sensitivity and therefore can be used in prognostic studies.</p>","PeriodicalId":54921,"journal":{"name":"Iranian Journal of Immunology","volume":"20 2","pages":"177-189"},"PeriodicalIF":0.9,"publicationDate":"2023-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9543318","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}