Publications by authors named "Shadi-Sadat Navabi"

8 Publications

  • Page 1 of 1

A Novel Non-frameshift ADA Deletion Detected by Whole Exome Sequencing in an Iranian Family with Severe Combined Immunodeficiency.

Iran J Allergy Asthma Immunol 2020 Feb 1;19(1):94-101. Epub 2020 Feb 1.

Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences (ZUMS), Zanjan, Iran.

Severe combined immunodeficiency (SCID) comprises a heterogeneous group of genetic disorders caused by early defects in the development and function of T cells. Other lymphocyte lineages (B and/or natural killer cells) are variably affected. With a worldwide frequency of approximately 1:50,000 live births, SCID may result from diverse mutations in over 16 genes. Whole-exome sequencing (WES) provides an opportunity for parallel screening of all those genes. This approach is also useful for genetic diagnosis in parents whose infant expired before genetic testing. Here, we describe a heterozygous novel non-frameshift deletion (c.587_598del p.196_199del) in the adenosine deaminase (ADA) gene identified by WES in healthy parents of an expired child with SCID. The mutation was subsequently confirmed to be homozygous in the deceased baby whose left-over blood sample volume was insufficient for direct WES analysis. In conclusion, we here describe a novel mutation in ADA, a well-known SCID gene.
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http://dx.doi.org/10.18502/ijaai.v19i1.2422DOI Listing
February 2020

Effects of guluronic acid (G2013) on SHIP1, SOCS1 induction and related molecules in TLR4 signaling pathway.

Int Immunopharmacol 2018 Feb 5;55:323-329. Epub 2018 Jan 5.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objective: This research aimed to study the anti-inflammatory and immunomodulatory effects of guluronic acid (G2013) on gene expression of TLR4, MyD88, SHIP1, SOCS1, NF-κB, and assessment of the level of IL-1β as a pro-inflammatory cytokine in HEK-Blue hTLR4 cell line.

Methods: The cytotoxicity of G2013 was assessed by the MTT assay. The mRNA expression levels of the mentioned genes were measured by qRT-PCR. IL-1β concentration in culture media was determined using ELISA method.

Results: MTT assay demonstrated that G2013 (before the concentration of 125μg/ml) had no cytotoxic effect on HEK-Blue hTLR4 cells. Our results indicated that the low and high doses of this drug could significantly reduce the gene expression of TLR4 and MyD88, as compared to the control group (p<0.05). Moreover, it was found that the low dose of this drug could significantly increase the gene expression of SHIP1 and SOCS1, as compared to the control group (p<0.05). Furthermore, the study findings revealed that the level of NF-κB gene expression significantly reduced, in both doses of G2013 compared to the control group (p<0.05, p<0.01, respectively). Our data showed that the level of IL-1β in culture media decreased by both doses of this drug in comparison to control group (p<0.05).

Conclusion: This study indicates that G2013 is able to induce SHIP1, SOCS1 and reduce TLR4, MyD88, NF-κB at the level of gene expression and decrease IL-1β as a pro-inflammatory cytokine which might be recommended for reduction of inflammatory reactions.
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http://dx.doi.org/10.1016/j.intimp.2018.01.003DOI Listing
February 2018

Hersintuzumab: A novel humanized anti-HER2 monoclonal antibody induces potent tumor growth inhibition.

Invest New Drugs 2018 04 6;36(2):171-186. Epub 2017 Oct 6.

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Humanized monoclonal antibodies (mAbs) against HER2 including trastuzumab and pertuzumab are widely used to treat HER2 overexpressing metastatic breast cancers. These two mAbs recognize distinct epitopes on HER2 and their combination induces a more potent blockade of HER2 signaling than trastuzumab alone. Recently, we have reported characterization of a new chimeric mAb (c-1T0) which binds to an epitope different from that recognized by trastuzumab and significantly inhibits proliferation of HER2 overexpressing tumor cells. Here, we describe humanization of this mAb by grafting all six complementarity determining regions (CDRs) onto human variable germline genes. Humanized VH and VL sequences were synthesized and ligated to human γ1 and κ constant region genes using splice overlap extension (SOE) PCR. Subsequently, the humanized antibody designated hersintuzumab was expressed and characterized by ELISA, Western blot and flow cytometry. The purified humanized mAb binds to recombinant HER2 and HER2-overexpressing tumor cells with an affinity comparable with the chimeric and parental mouse mAbs. It recognizes an epitope distinct from those recognized by trastuzumab and pertuzumab. Binding of hersintuzumab to HER2 overexpressing tumor cells induces G1 cell cycle arrest, inhibition of ERK and AKT signaling pathways and growth inhibition. Moreover, hersintuzumab could induce antibody-dependent cell cytotoxicity (ADCC) on BT-474 cells. This new humanized mAb is a potentially valuable tool for single or combination breast cancer therapy.
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http://dx.doi.org/10.1007/s10637-017-0518-0DOI Listing
April 2018

Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory effects on peripheral blood mononuclear cells activation.

Int Immunopharmacol 2017 Jun 30;47:59-69. Epub 2017 Mar 30.

Department of Immunology and Microbiology, School of Medicine, Jahrom University of Medical Sciences, Jahrom, Iran.

Background And Objectives: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines.

Materials And Methods: PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively.

Results: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs.

Conclusions: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.
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http://dx.doi.org/10.1016/j.intimp.2017.03.016DOI Listing
June 2017

IL-17 and IL-22 genetic polymorphisms in HBV vaccine non- and low-responders among healthcare workers.

Germs 2016 Mar 1;6(1):14-20. Epub 2016 Mar 1.

MD, PhD, Clinical Virologist, Hepatitis B Molecular Laboratory, Department of Virology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Background: Healthcare workers constitute a population at high risk for HBV infection. Efficient vaccination options are available; however, the individual response to HBV vaccination may vary widely between subjects, potentially due to cytokine profiles and genetic variations. In the present study, we investigated the relationship between IL-17 and IL-22 gene polymorphisms versus non- and low-responsiveness to HBV vaccination in healthcare workers.

Methods: We selected the following IL-17 and IL-22 polymorphisms: rs4711998 (A/G) from IL-17 and rs2227501 (A/T), rs2227503 (A/G), rs1026786 (A/G) from IL-22 sequences genes. These were determined by polymerase chain reaction restriction fragment length polymorphisms.

Results: The IL-17 rs4711998 GG genotype had a significantly lower frequency in non-responders compared to low-responders (p=0.025). However, we did not identify a relationship between IL-22 rs1026780, rs2227501 and rs2227503 genotypes and the anti-HBs response following HBV vaccination.

Conclusion: These data suggest that genetic variation in rs4711998 polymorphisms in the IL-17 cytokine may influence vaccine-induced immune responses to HBV vaccine in healthcare workers.
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http://dx.doi.org/10.11599/germs.2016.1084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4788777PMC
March 2016

Restricted antibody response to Bordetella pertussis filamentous hemagglutinin induced by whole-cell and acellular pertussis vaccines.

Infect Dis (Lond) 2016 Feb 6;48(2):127-32. Epub 2015 Oct 6.

a Department of Immunology , School of Public Health, Tehran University of Medical Sciences , Tehran , Iran .

Background: Filamentous hemagglutinin (FHA) is a principal virulence factor, an important immunogenic antigen of Bordetella pertussis, and a major component of many acellular pertussis vaccines. In the present study, the human antibody response to different regions of FHA was determined in healthy children and adults vaccinated with either whole-cell or acellular pertussis vaccines.

Methods: To define the immunodominant regions of FHA, four overlapping recombinant fragments were expressed and produced in Escherichia coli and then purified by His-tagged based affinity chromatography. Two groups comprising healthy preschool children (n = 50) and adults (n = 26) were vaccinated with a single dose of commercial whole-cell and acellular DTaP vaccines, respectively. An antigen-based ELISA was applied to measure serum levels of anti-FHA antibody to both native and recombinant proteins in vaccinated volunteers.

Results: In both groups of vaccinated individuals, the anti-FHA antibody response was mainly directed against epitopes located within a fragment of FHA spanning amino acid residues 1877-2250 of the mature FHA molecule (p < 0.001). No or little antibody was detected against the other recombinant segments of FHA.

Conclusion: Our results suggest that the human antibody response to FHA is directed to an immunodominant region located within residues 1877-2250 of the FHA molecule. Characterization and epitope mapping of the major components of acellular pertussis vaccine and future modifications in vaccine formulation may improve its efficacy and protectivity.
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http://dx.doi.org/10.3109/23744235.2015.1093655DOI Listing
February 2016

The Newly Identified T Helper 22 Cells Lodge in Leukemia.

Int J Hematol Oncol Stem Cell Res 2015 Jul;9(3):143-54

Department of Immunology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran.

Leukemia is a hematological tumor in which the malignant myeloid or lymphoid subsets play a pivotal role. Newly identified T helper cell 22 (Th22) is a subset of CD4(+) T cells with distinguished gene expression, function and specific properties apart from other known CD4(+) T cell subsets.Th22 cells are characterized by production of a distinct profile of effector cytokines, including interleukin (IL)-22, IL-13, and tumor necrosis factor-α (TNF-α). The levels of Th22 and cytokine IL-22 are increased and positively related to inflammatory and autoimmune disorders. Recently, several studies have reported the changes in frequency and function of Th22 in acute leukemic disorders as AML and ALL. This review discusses the role of Th22 and its cytokine IL-22 in the immunopathogenesis of leukemic disease.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529682PMC
July 2015

Natural Killer Cell Functional Activity After 4-1BB Costimulation.

Inflammation 2015 ;38(3):1181-90

Department of Immunology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.

Reports show enhancement of CD8 T cells' activity through CD137 (4-1BB) signal; however, not all data proved similar effect in natural killer (NK) cells. Here, the impact of 4-1BB signal on NK cells' function was assessed during short term cultures. To that end, cytokine-activated NK cells were cocultured with adenovirally transduced MCF-7 stimulator cells expressing 4-1BB ligand. Cellular cytotoxicity, cytokine production, and expression of cytotoxicity related genes were assessed after overnight cultures. Sharp decrease of CD56+ and CD56bright NK cells was demonstrated. 4-1BB neither enhanced cellular degranulation nor improved IFN-γ production although it promoted granzyme B, perforin, and FasL gene expression. 4-1BB signal stimulated higher proportions of CD56bright population to degranulate and express CD107a; however, it could not recover killing activity against K562 targets. Our data could not show major promotion in activity of all NK subpopulations. Due to great heterogeneity of NK cells, more investigation is needed to draw a comprehensive conclusion.
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http://dx.doi.org/10.1007/s10753-014-0082-0DOI Listing
February 2016