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Article ; Online: Immune Profiling of SARS-CoV-2; What We Know and What We Don’t Know

Mahshid Zohouri / Atri Ghods / Mina Roshan Zamir / Fazel Shokri / Abbas Ghaderi

Iranian Journal of Allergy, Asthma and Immunology, Vol 22, Iss

2023 Volume 3

Abstract: Coronavirus disease 2019 (COVID-19), described as World War 3, is the current worldwide health challenge and nearly all countries have so far faced this disaster. There is still no cure because of the complicated pathogenesis, however, there are several ... ...

Abstract	Coronavirus disease 2019 (COVID-19), described as World War 3, is the current worldwide health challenge and nearly all countries have so far faced this disaster. There is still no cure because of the complicated pathogenesis, however, there are several studies on track investigating different aspects of the immune response to the virus. In this review, we will provide an overview of recent investigations that have analyzed immune cells in patients with COVID-19. We will then discuss the differences in immune profiles between healthy controls and various clinical presentations, including asymptomatic, mild, moderate, and severe cases.
Keywords	Adaptive immunity ; Coronavirus disease 2019 ; Immunology ; Innate immunity ; Physiopathology ; Severe acute respiratory syndrome coronavirus 2 ; Medicine ; R
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Novel Monoclonal Antibodies Specific for Human Ki67 and P53 Tumor Markers in Breast Cancer Tissue Samples

Masoud Hassanzadeh Makoui / Maryam Mobini / Jalal Khoshnoodi / Tannaz Bahadori / Forough Golsaz-Shirazi / Hedieh Moradi Tabriz / Zahra Madjd / Mahmood Jeddi-Tehrani / Amir-Hassan Zarnani / Mohammad Mehdi Amiri / Fazel Shokri

Iranian Journal of Immunology, Vol 20, Iss 2, Pp 177-

2023 Volume 189

Abstract: Background: 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 ... ...

Abstract	Background: 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.Objective: To generate and characterize novel monoclonal antibodies (mAbs) against human Ki67 and P53 antigens for IHC purposes.Methods: 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.Results: 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.Conclusion: 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.
Keywords	immunohistochemistry ; ki67 ; monoclonal antibody ; p53 ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-06-01T00:00:00Z
Publisher	Shiraz University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Endometrial mesenchymal stem/stromal cells

Mehdi Aleahmad / Mahmood Bozorgmehr / Shohreh Nikoo / Alireza Ghanavatinejad / Mohammad-Reza Shokri / Samaneh Montazeri / Fazel Shokri / Amir-Hassan Zarnani

Stem Cell Research & Therapy, Vol 12, Iss 1, Pp 1-

The Enigma to code messages for generation of functionally active regulatory T cells

2021 Volume 15

Abstract: Abstract Background Regulatory T cells (Tregs) play an important role in fine-tuning of immune responses and are pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs ...

Abstract	Abstract Background Regulatory T cells (Tregs) play an important role in fine-tuning of immune responses and are pivotal for a successful pregnancy. Recently, the importance of mesenchymal stem cells in regulation of immune responses in general and Tregs in particular has been highlighted. Here, we hypothesized that menstrual stromal/stem cells (MenSCs) contribute to uterine immune system regulation through induction of functionally active Tregs. Methods MenSCs were collected from 18 apparently healthy women and characterized. Bone marrow mesenchymal stem cells (BMSCs) served as a control. The effect of MenSCs on proliferation of anti-CD3/CD28-stimulated T CD4 + cells and generation of Tregs with or without pre-treatment with mitomycin C, IFN-γ and IL-1β was evaluated by flow cytometry. The potential role of IDO, PGE2, IL-6, IL-10, and TGF-β on proliferation of T CD4 + cells and generation of Tregs was assessed using blocking antibodies or agents. IDO activity was evaluated in MenSCs and BMSCs culture supernatants by a colorimetric assay. IL-10 and IFN-γ production in MenSCs-primed T CD4 + was measured using intracellular staining. To investigate the functional properties of Tregs induced by MenSCs, Treg cells were isolated and their functional property to inhibit proliferation of anti-CD3/CD28-stimulated PBMCs was assessed by flow cytometry. Results According to the results, proliferation of T CD4 + lymphocytes was enhanced in the presence of MenSCs, while pre-treatment of MenSCs with pro-inflammatory cytokines reversed this effect. PGE2 and IDO were the major players in MenSCs-induced T cell proliferation. Non-treated MenSCs decreased the frequency of Tregs, whereas after pre-treatment with IFN-γ and IL-1β, they induced functional Tregs with ability to inhibit the proliferation of anti-CD3/CD28-stimulated PBMCs. This effect was mediated through IL-6, IL-10, TGF-β and IDO. IFN-γ/IL-1β-treated MenSCs induced IL-10 and IFN-γ production in CD4 + T cells. Conclusion Collectively, these findings indicate that ...
Keywords	MenSCs ; Regulatory T cells ; Proliferation ; Endometrium ; Pregnancy ; Immunomodulation ; Medicine (General) ; R5-920 ; Biochemistry ; QD415-436
Subject code	570
Language	English
Publishing date	2021-10-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Overall status of Epstein-Barr virus infection, IFN-α, and TLR-7/9 in patients with Systemic Lupus Erythematosus

Sayed Mahdi Marashi / Shima Izadi / Seyed Reza Najafizadeh / Ahmad Nejati / Majid Teymoori-Rad / Shohreh Shahmahmoodi / Forough Golsaz-Shirazi / Fazel Shokri

Iranian Journal of Immunology, Vol 18, Iss 3, Pp 230-

2021 Volume 240

Abstract: Background: Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder. While studying the pathogenesis of SLE is prevalent, both infectious and non-infectious elements are regarded to exert an important impact on the disease's development. ... ...

Abstract	Background: Systemic lupus erythematous (SLE) is a multisystem autoimmune disorder. While studying the pathogenesis of SLE is prevalent, both infectious and non-infectious elements are regarded to exert an important impact on the disease's development. Objective: To explore the overall status of EBV, TLR7, TLR9, and IFN-α gene expression in 32 patients suffering from SLE and 32 healthy controls. Methods: Plasma and PBMCs were separated from fresh whole blood. To measure EBV DNA load and mRNA levels of IFN-a, TLR-7 and9 in PBMCs, molecular techniques were employed. The production of IFN-α, ds-DNA IgG antibody, and EBNA-1 IgG levels were also measured in plasma by ELISA. Results: SLE patients showed significantly higher EBV load (p=0.001) and transcriptional levels of TLR7 (p=0.0001), IFN-α (p=0.0001), and TLR9 (p=0.0001) than controls. Moreover, the plasma levels of IFN-α (p=0.0002) and EBNA-1specific IgG antibodies (p=0.01) were significantly higher in SLE patients. Conclusion: The results stressed on the potential role of EBV infection and TLRs in SLE patients although more research is needed to determine the global impact that EBV infection can have on immune signature in patients with SLE.
Keywords	epstein-barr virus ; ifn-α ; systemic lupus erythematous ; toll-like receptors ; Biology (General) ; QH301-705.5
Subject code	610
Language	English
Publishing date	2021-09-01T00:00:00Z
Publisher	Shiraz University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TH1 and TH2 Responses Are Influenced by HLA Antigens in Healthy Neonates Vaccinated with Recombinant Hepatitis B Vaccine

Abdollah Jafarzadeh / Fazel Shokri

Iranian Journal Of Allergy, Asthma and Immunology, Vol 11, Iss 4, Pp 308-

2012 Volume 315

Abstract: The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on ... ...

Abstract	The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on cytokine secretion by HBsAg-stimulated peripheral blood mononuclear cells (PBMC) from healthy neonates vaccinated with recombinant HBsAg.Peripheral blood mononuclear cells (PBMC) were isolated from 48 Iranian neonates vaccinated with a recombinant HBV vaccine. The cells were stimulated in vitro with rHBsAg and the concentration of IL-4, IL-10, IL-12 and IFN-γ were quantitated in culture supernatant by sandwich ELISA. HLA typing was performed by microlymphocytotoxicity method.Significant diminished secretion of both Th1 (IFN-γ) and Th2 (IL-4, IL-10) cytokines was observed in HBsAg-stimulated PBMC from vaccinees expressing the HLA-DR7 compared to DR7 negative vaccinees. Similarly, lower production of these cytokines was also observed in vaccinees with DR7-DR53-DQ2, B7-DR7-DR53-DQ2 and A2-DR7-DR53-DQ2 haplotypes (p<0.05, p <0.005). While HBsAg-stimulated PBMC of DR13+ subjects produced lower levels of Th2-type cytokines (IL-4 and IL-10), those of HLA-B8+ or HLA-A9+ subjects produced higher levels of Th2-type cytokines. Cytokine secretion in response to PHA mitogen was not associated with a given HLA antigen or haplotype and was similarly represented in all groups of subjects irrespective of their HLA complex.These results indicate that HLA antigens may differentially influence cytokine secretion by HBsAg-specific T-cells of healthy neonates vaccinated with recombinant HB vaccine. This phenomenon may have an important implication for control of the immune response to HBsAg vaccine.
Keywords	Cytokine ; Hepatitis B vaccine ; HLA antigens ; Immunologic diseases. Allergy ; RC581-607 ; Specialties of internal medicine ; RC581-951 ; Internal medicine ; RC31-1245 ; Medicine ; R ; DOAJ:Allergy and Immunology ; DOAJ:Medicine (General) ; DOAJ:Health Sciences
Subject code	610 ; 570
Language	English
Publishing date	2012-12-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TH1 and TH2 Responses Are Influenced by HLA Antigens in Healthy Neonates Vaccinated with Recombinant Hepatitis B Vaccine

Abdollah Jafarzadeh / Fazel Shokri

Iranian Journal of Allergy, Asthma and Immunology, Vol 11, Iss

2012 Volume 4

Abstract	The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on cytokine secretion by HBsAg-stimulated peripheral blood mononuclear cells (PBMC) from healthy neonates vaccinated with recombinant HBsAg. PBMCs were isolated from 48 Iranian neonates vaccinated with a recombinant HBV vaccine. The cells were stimulated in vitro with rHBsAg and the concentration of IL-4, IL-10, IL-12 and IFN-γ were quantitated in culture supernatant by sandwich ELISA. HLA typing was performed by microlymphocytotoxicity method. Significant diminished secretion of both Th1 (IFN-γ) and Th2 (IL-4, IL-10) cytokines was observed in HBsAg-stimulated PBMC from vaccinees expressing the HLA-DR7 compared to DR7 negative vaccinees. Similarly, lower production of these cytokines was also observed in vaccinees with DR7-DR53-DQ2, B7-DR7-DR53-DQ2 and A2-DR7-DR53-DQ2 haplotypes (p<0.05, p <0.005). While HBsAg-stimulated PBMC of DR13+ subjects produced lower levels of Th2-type cytokines (IL-4 and IL-10), those of HLA-B8+ or HLA-A9+ subjects produced higher levels of Th2-type cytokines. Cytokine secretion in response to PHA mitogen was not associated with a given HLA antigen or haplotype and was similarly represented in all groups of subjects irrespective of their HLA complex. These results indicate that HLA antigens may differentially influence cytokine secretion by HBsAg-specific T-cells of healthy neonates vaccinated with recombinant HB vaccine. This phenomenon may have an important implication for control of the immune response to HBsAg vaccine.
Keywords	Cytokine ; Hepatitis B vaccine ; HLA antigens ; Medicine ; R
Subject code	570 ; 610
Language	English
Publishing date	2012-12-01T00:00:00Z
Publisher	Tehran University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Human menstrual blood-derived stromal/stem cells modulate functional features of natural killer cells

Mohammad-Reza Shokri / Mahmood Bozorgmehr / Alireza Ghanavatinejad / Reza Falak / Mehdi Aleahmad / Somaieh Kazemnejad / Fazel Shokri / Amir-Hassan Zarnani

Scientific Reports, Vol 9, Iss 1, Pp 1-

2019 Volume 13

Abstract: Abstract Although natural killer (NK) cells play a crucial role in the maintenance of a successful pregnancy, their cytotoxic activity should be tightly controlled. We hypothesized that endometrial mesenchymal stromal/stem cells (eMSCs) could potentially ...

Abstract	Abstract Although natural killer (NK) cells play a crucial role in the maintenance of a successful pregnancy, their cytotoxic activity should be tightly controlled. We hypothesized that endometrial mesenchymal stromal/stem cells (eMSCs) could potentially attenuate the functional features of NK cells. Herein, we assessed immunomodulatory effects of menstrual blood-derived stromal/stem cells (MenSCs), as a surrogate for eMSCs, on NK cells function. Our results showed that MenSCs induced proliferation of NK cells. However, IFN-γ/IL-1β pretreated MenSCs significantly inhibited NK cell proliferation. Of 41 growth factors tested, MenSCs produced lower levels of insulin-like growth factor binding proteins (IGFBPs) 1–4, VEGF-A, β-NGF, and M-CSF compared to bone marrow-derived mesenchymal stem cells (BMSCs). MenSCs displayed high activity of IDO upon IFN-γ treatment. The antiproliferative potential of IFN-γ/IL-1β-pretreated MenSCs was mediated through IL-6 and TGF-β. MenSCs impaired the cytotoxic activity of NK cells on K562 cells, consistent with the lower expression of perforin, granzymes A, and B. We also observed that in vitro decidualization of MenSCs in the presence of IFN-γ reduced the inhibitory effect of MenSCs on NK cell cytotoxicity against K562 target cells. Additionally, MenSCs were found to be prone to NK cell-mediated lysis in an MHC-independent manner. Our findings imply that dysregulation of NK cells in such pregnancy-related disorders as miscarriage may stem from dysfunctioning of eMSCs.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Does prior immunization with measles, mumps, and rubella vaccines contribute to the antibody response to COVID-19 antigens?

Danesh Hassani / Mohammad Mehdi Amiri / Faezeh Maghsood / Vahid Salimi / Gholam Ali Kardar / Omid Barati / Seyed Mohammad Reza Hashemian / Mahmood Jeddi-Tehrani / Amir-Hassan Zarnani / Fazel Shokri

Iranian Journal of Immunology, Vol 18, Iss 1, Pp 47-

2021 Volume 53

Abstract: Background: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. ... ...

Abstract	Background: Incidence and severity of SARS-CoV2 infection are significantly lower in children and teenagers proposing that certain vaccines, routinely administered to neonates and children may provide cross-protection against this emerging infection. Objective: To assess the cross-protection induced by prior measles, mumps and rubella (MMR) vaccinations against COVID-19. Methods: The antibody responses to MMR and tetanus vaccines were determined in 53 patients affected with SARS-CoV2 infection and 52 age-matched healthy subjects. Serum levels of antibodies specific for NP and RBD of SARS-CoV2 were also determined in both groups of subjects with ELISA. Results: Our results revealed significant differences in anti-NP (p <0.0001) and anti-RBD (p <0.0001) IgG levels between patients and healthy controls. While the levels of rubella- and mumps specific IgG were not different in the two groups of subjects, measles-specific IgG was significantly higher in patients (p <0.01). The serum titer of anti-tetanus antibody, however, was significantly lower in patients compared to healthy individuals (p <0.01). Conclusion: Our findings suggest that measles vaccination triggers those B cells cross-reactive with SARS-CoV2 antigens leading to the production of increased levels of measles-specific antibody.
Keywords	antibody response ; cross-protection ; mmr ; sars-cov2 ; tetanus ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	Shiraz University of Medical Sciences
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Development of a Novel Inhibitory Chimeric Anti-HER2 Monoclonal Antibody

Mohammad Mehdi Amiri / Tannaz Bahadori / Tahereh Soltantoyeh / Reza Hosseini-Ghatar / Forough Golsaz-Shirazi / Mahmood Jeddi-Tehrani / Fazel Shokri

Iranian Journal of Immunology, Vol 16, Iss 1, Pp 26-

2019 Volume 42

Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2019-03-01T00:00:00Z
Publisher	Shiraz University of Medical Sciences
Document type	Article ; Online
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Article ; Online: Epitope mapping of severe acute respiratory syndrome coronavirus 2 neutralizing receptor binding domain-specific monoclonal antibodies

Faezeh Maghsood / Mohammad Mehdi Amiri / Amir-Hassan Zarnani / Vahid Salimi / Gholam Ali Kardar / Jalal Khoshnoodi / Maryam Mobini / Hengameh Ahmadi Zare / Abbas Ghaderi / Mahmood Jeddi-Tehrani / Sylvie Schmidt / Géraldine Laumond / Christiane Moog / Fazel Shokri

Frontiers in Medicine, Vol

2022 Volume 9

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the outbreak led to the coronavirus disease 2019 (COVID-19) pandemic. Receptor binding domain (RBD) of spike (S) protein of SARS-CoV-2 is considered as a major target ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the outbreak led to the coronavirus disease 2019 (COVID-19) pandemic. Receptor binding domain (RBD) of spike (S) protein of SARS-CoV-2 is considered as a major target for immunotherapy and vaccine design. Here, we generated and characterized a panel of anti-RBD monoclonal antibodies (MAbs) isolated from eukaryotic recombinant RBD-immunized mice by hybridoma technology. Epitope mapping was performed using a panel of 20-mer overlapping peptides spanning the entire sequence of the RBD protein from wild-type (WT) Wuhan strain by enzyme-linked immunosorbent assay (ELISA). Several hybridomas showed reactivity toward restricted RBD peptide pools by Pepscan analysis, with more focus on peptides encompassing aa 76–110 and 136–155. However, our MAbs with potent neutralizing activity which block SARS-CoV-2 spike pseudovirus as well as the WT virus entry into angiotensin-converting enzyme-2 (ACE2) expressing HEK293T cells showed no reactivity against these peptides. These findings, largely supported by the Western blotting results suggest that the neutralizing MAbs recognize mainly conformational epitopes. Moreover, our neutralizing MAbs recognized the variants of concern (VOC) currently in circulation, including alpha, beta, gamma, and delta by ELISA, and neutralized alpha and omicron variants at different levels by conventional virus neutralization test (CVNT). While the neutralization of MAbs to the alpha variant showed no substantial difference as compared with the WT virus, their neutralizing activity was lower on omicron variant, suggesting the refractory effect of mutations in emerging variants against this group of neutralizing MAbs. Also, the binding reactivity of our MAbs to delta variant showed a modest decline by ELISA, implying that our MAbs are insensitive to the substitutions in the RBD of delta variant. Our data provide important information for understanding the immunogenicity of RBD, and the potential application of the ...
Keywords	COVID-19 ; monoclonal antibodies ; neutralization ; omicron ; SARS-CoV-2 ; Medicine (General) ; R5-920
Subject code	570
Language	English
Publishing date	2022-09-01T00:00:00Z
Publisher	Frontiers Media S.A.
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