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Article ; Online: The Role of Coinhibitory Receptors in B Cell Dysregulation in SARS-CoV-2-Infected Individuals with Severe Disease.

Saito, Suguru / Bozorgmehr, Najmeh / Sligl, Wendy / Osman, Mohammed / Elahi, Shokrollah

Journal of immunology (Baltimore, Md. : 1950)

2024

Abstract: Severe SARS-CoV-2 infection is associated with significant immune dysregulation involving different immune cell subsets. In this study, when analyzing critically ill COVID-19 patients versus those with mild disease, we observed a significant reduction in ...

Abstract	Severe SARS-CoV-2 infection is associated with significant immune dysregulation involving different immune cell subsets. In this study, when analyzing critically ill COVID-19 patients versus those with mild disease, we observed a significant reduction in total and memory B cell subsets but an increase in naive B cells. Moreover, B cells from COVID-19 patients displayed impaired effector functions, evidenced by diminished proliferative capacity, reduced cytokine, and Ab production. This functional impairment was accompanied by an increased apoptotic potential upon stimulation in B cells from severely ill COVID-19 patients. Our further studies revealed the expansion of B cells expressing coinhibitory molecules (PD-1, PD-L1, TIM-1, VISTA, CTLA-4, and Gal-9) in intensive care unit (ICU)-admitted patients but not in those with mild disease. The coinhibitory receptor expression was linked to altered IgA and IgG expression and increased the apoptotic capacity of B cells. Also, we found a reduced frequency of CD24hiCD38hi regulatory B cells with impaired IL-10 production. Our mechanistic studies revealed that the upregulation of PD-L1 was linked to elevated plasma IL-6 levels in COVID-19 patients. This implies a connection between the cytokine storm and altered B cell phenotype and function. Finally, our metabolomic analysis showed a significant reduction in tryptophan but elevation of kynurenine in ICU-admitted COVID-19 patients. We found that kynurenine promotes PD-L1 expression in B cells, correlating with increased IL-6R expression and STAT1/STAT3 activation. Our observations provide novel insights into the complex interplay of B cell dysregulation, implicating coinhibitory receptors, IL-6, and kynurenine in impaired B cell effector functions, potentially contributing to the pathogenesis of COVID-19.
Language	English
Publishing date	2024-03-22
Publishing country	United States
Document type	Journal Article
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2300783
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Article: Depletion of polyfunctional CD26

Bozorgmehr, Najmeh / Hnatiuk, Mark / Peters, Anthea C / Elahi, Shokrollah

Experimental hematology & oncology

2023 Volume 12, Issue 1, Page(s) 13

Abstract: Background: CD8: Methods: We studied 55 CLL and 44 age-sex-matched healthy controls (HCs). The expression of CD26 on different T cell subsets (e.g. naïve, memory, effector, and etc.) was analyzed. Also, functional properties of CD8: Results: CD26 ... ...

Abstract	Background: CD8 Methods: We studied 55 CLL and 44 age-sex-matched healthy controls (HCs). The expression of CD26 on different T cell subsets (e.g. naïve, memory, effector, and etc.) was analyzed. Also, functional properties of CD8 Results: CD26 expression identifies three CD8 Conclusions: Our results demonstrate that CD26
Language	English
Publishing date	2023-01-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2669066-4
ISSN	2162-3619
ISSN	2162-3619
DOI	10.1186/s40164-023-00375-5
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Article ; Online: Transcriptomic profiling of peripheral blood cells in HPV-associated carcinoma patients receiving combined valproic acid and avelumab.

Bozorgmehr, Najmeh / Syed, Hussain / Mashhouri, Siavash / Walker, John / Elahi, Shokrollah

Molecular oncology

2023

Abstract: Human papillomavirus (HPV)-associated cancer continues to evade the immune system by promoting a suppressive tumor microenvironment. Therefore, immunotherapy appears to be a promising approach for targeting HPV-associated tumors. We hypothesized that ... ...

Abstract	Human papillomavirus (HPV)-associated cancer continues to evade the immune system by promoting a suppressive tumor microenvironment. Therefore, immunotherapy appears to be a promising approach for targeting HPV-associated tumors. We hypothesized that valproic acid (VA) as an epigenetic agent combined with avelumab may enhance the antitumor immunity in HPV-associated solid tumors. We performed bulk RNA-sequencing (RNA-Seq) on total peripheral blood mononuclear cells (PBMCs) of seven nonresponders (NRs) and four responders (Rs). A total of 39 samples (e.g., pretreatment, post-VA, postavelumab, and endpoint) were analyzed. Also, we quantified plasma analytes and performed flow cytometry. We observed a differential pattern in immune response following treatment with VA and/or avelumab in NRs vs. Rs. A significant upregulation of transcripts associated with NETosis [the formation of neutrophil extracellular traps (NETs)] and neutrophil degranulation pathways was linked to the presence of a myeloid-derived suppressor cell signature in NRs. We noted the elevation of IL-8/IL-18 cytokines and a distinct transcriptome signature at the baseline and endpoint in NRs. By using the receiver operator characteristics, we identified a cutoff value for the plasma IL-8/IL-18 to discriminate NRs from Rs. We found differential therapeutic effects for VA and avelumab in NRs vs. Rs. Thus, our results imply that measuring the plasma IL-8/IL-18 and bulk RNA-Seq of PBMCs may serve as valuable biomarkers to predict immunotherapy outcomes.
Language	English
Publishing date	2023-09-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	2415106-3
ISSN	1878-0261 ; 1574-7891
ISSN (online)	1878-0261
ISSN	1574-7891
DOI	10.1002/1878-0261.13519
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Article ; Online: CD71

Bozorgmehr, Najmeh / Okoye, Isobel / Mashhouri, Siavash / Lu, Julia / Koleva, Petya / Walker, John / Elahi, Shokrollah

Journal for immunotherapy of cancer

2023 Volume 11, Issue 5

Abstract: Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. However, only a portion of patients respond to such treatments. Therefore, it remains a prevailing clinical need to identify factors associated with acquired ... ...

Abstract	Background: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer. However, only a portion of patients respond to such treatments. Therefore, it remains a prevailing clinical need to identify factors associated with acquired resistance or lack of response to ICIs. We hypothesized that the immunosuppressive CD71 Methods: We studied 38 patients with cancer through a phase II clinical trial investigating the effects of oral valproate combined with avelumab (anti-programmed death-ligand 1 (PD-L1)) in virus-associated solid tumors (VASTs). We quantified the frequency/functionality of CECs in blood and biopsies of patients. Also, we established an animal model of melanoma (B16-F10) to investigate the possible effects of erythropoietin (EPO) treatment on anti-PD-L1 therapy. Results: We found a substantial expansion of CECs in the blood of patients with VAST compared with healthy controls. We noted that the frequency of CECs in circulation was significantly higher at the baseline and throughout the study in non-responders versus responders to PD-L1 therapy. Moreover, we observed that CECs in a dose-dependent manner suppress effector functions of autologous T cells in vitro. The subpopulation of CD45 Conclusions: Our results demonstrate that anemia by the expansion of CECs may enhance cancer progression. Notably, measuring the frequency of CECs may serve as a valuable biomarker to predict immunotherapy outcomes.
MeSH term(s)	Humans ; Animals ; Mice ; T-Lymphocytes/pathology ; Immunotherapy/methods ; Melanoma ; Erythroid Cells/pathology ; Neoplasm Staging ; Tumor Microenvironment
Language	English
Publishing date	2023-06-06
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2719863-7
ISSN	2051-1426 ; 2051-1426
ISSN (online)	2051-1426
ISSN	2051-1426
DOI	10.1136/jitc-2022-006595
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Article ; Online: Analysis of SARS-CoV-2 isolates, namely the Wuhan strain, Delta variant, and Omicron variant, identifies differential immune profiles.

Shahbaz, Shima / Bozorgmehr, Najmeh / Lu, Julia / Osman, Mohammed / Sligl, Wendy / Tyrrell, D Lorne / Elahi, Shokrollah

Microbiology spectrum

2023 , Page(s) e0125623

Abstract: There is an urgent need to better understand the impact of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on immune response and disease dynamics to facilitate better intervention strategies. Here, we show that SARS-CoV-2 ...

Abstract	There is an urgent need to better understand the impact of different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants on immune response and disease dynamics to facilitate better intervention strategies. Here, we show that SARS-CoV-2 variants differentially affect host immune responses. The magnitude and quantity of cytokines and chemokines were comparable in those infected with the Wuhan strain and the Delta variant. However, individuals infected with the Omicron variant had significantly lower levels of these mediators. We also found an elevation of plasma galectins (Gal-3, Gal-8, and Gal-9) in infected individuals, in particular, in those with the original strain. Soluble galectins exert a proinflammatory role in COVID-19 pathogenesis. This was illustrated by their correlation with the plasma levels of sCD14, sCD163, enhanced TNF-α/IL-6 secretion, and increased SARS-CoV-2 infectivity
Language	English
Publishing date	2023-09-07
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.01256-23
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Article ; Online: Investigation the Effect of Micelle Nanoparticles Containing Curcumin on Ciprofloxacin Resistant Isolates of Pseudomonas Aeruginosa and on mexC and mexD Genes Expression

Bozorgmehr Imani Pirsaraei / Najmeh Ranji / Leila Asadpour

Majallah-i dānishgāh-i ̒ulūm-i pizishkī-i Arāk, Vol 21, Iss 2, Pp 10-

2018 Volume 20

Abstract: Abstract Background: Pseudomonas aeruginosa is an opportunistic gram-negative bacterium that is a major cause of nosocomial infections such as severe burns. Curcumin is the main component of turmeric (Curcuma longa) that has anti-cancer and anti- ... ...

Abstract	Abstract Background: Pseudomonas aeruginosa is an opportunistic gram-negative bacterium that is a major cause of nosocomial infections such as severe burns. Curcumin is the main component of turmeric (Curcuma longa) that has anti-cancer and anti-inflammatory effects. The aim of this study was to evaluate antibacterial effect of curcumin in ciprofloxacin resistant isolates of Pseudomonas aeruginosa through mexC and mexD gene expression. Materials and Methods: In this descriptive-analytical study, Pseudomonas aeruginosa strains were obtained from hospitals and laboratories in Guilan province. After disc difusion and MIC tests, four ciprofloxacin resistant strains of Pseudomonas aeruginosa were treated by ciprofloxacin (1/2MIC) only (control sample) and in the combination with curcumin encapsulated in micelle nanoparticles (test sample). After 24h, RNA extraction and cDNA synthesis was performed. Then, the expression of mexC and mexD genes was evaluated quantitatively by Real-time PCR method in curcumin treated and un-treated cells Results: This study showed that combination of ciprofloxacin (1/2 MIC) with curcumin encapsulated in micelle nanoparticles led to approximately 50% of growth inhibition in Pseudomonas aeruginosa. In treated cells with curcumin and ciprofloxacin compared to treated cells with ciprofloxacin alone, mexC and mexD genes were significantly (p<0.05) downregulated >0.65 fold in three isolates and >0.1 fold in four isolates, respectively. Conclusion: Our results suggested that curcumin encapsulated in micelle nanoparticles combined with 1/2 MIC value of ciprofloxacin inhibits the growth of Pseudomonas aeruginosa through reducing mexC and mexD expression.
Keywords	Ciprofloxacin ; curcumin ; mexC ; mexD ; micelle nanoparticles ; Pseudomonas Aeruginosa ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	616
Language	Persian
Publishing date	2018-05-01T00:00:00Z
Publisher	Arak Medical University
Document type	Article ; Online
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Article ; Online: CD71

Delyea, Cole / Bozorgmehr, Najmeh / Koleva, Petya / Dunsmore, Garett / Shahbaz, Shima / Huang, Vivian / Elahi, Shokrollah

Journal of immunology (Baltimore, Md. : 1950)

2018 Volume 200, Issue 12, Page(s) 4044–4058

Abstract: Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother's immune rejection as the fetus is ... ...

Abstract	Survival of the allogeneic pregnancy depends on the maintenance of immune tolerance to paternal alloantigens at the fetomaternal interface. Multiple localized mechanisms contribute to the fetal evasion from the mother's immune rejection as the fetus is exposed to a wide range of stimulatory substances such as maternal alloantigens, microbes and amniotic fluids. In this article, we demonstrate that CD71
MeSH term(s)	Animals ; Antigens, CD/immunology ; Arginase/immunology ; B7-H1 Antigen/immunology ; Erythroid Cells/immunology ; Female ; Humans ; Immune Tolerance/immunology ; Immunosuppression/methods ; Interferon-gamma/immunology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Pregnancy ; Receptors, Transferrin/immunology ; Th2 Cells/immunology ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	Antigens, CD ; B7-H1 Antigen ; CD71 antigen ; Cd274 protein, mouse ; Receptors, Transferrin ; Tumor Necrosis Factor-alpha ; Interferon-gamma (82115-62-6) ; Arg2 protein, mouse (EC 3.5.3.1) ; Arginase (EC 3.5.3.1)
Language	English
Publishing date	2018-05-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1800113
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Article ; Online: Galectin-9, a Player in Cytokine Release Syndrome and a Surrogate Diagnostic Biomarker in SARS-CoV-2 Infection.

Bozorgmehr, Najmeh / Mashhouri, Siavash / Perez Rosero, Eliana / Xu, Lai / Shahbaz, Shima / Sligl, Wendy / Osman, Mohammed / Kutsogiannis, Demetrios J / MacIntyre, Erika / O'Neil, Conar R / Elahi, Shokrollah

mBio

2021 Volume 12, Issue 3

Abstract: The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. In this study, we observed massive elevation of ... ...

Abstract	The outbreak of SARS-CoV-2 infection has enormously impacted our lives. Clinical evidence has implicated the emergence of cytokine release syndrome as the prominent cause of mortality in COVID-19 patients. In this study, we observed massive elevation of plasma Galectin-9 (Gal-9) in COVID-19 patients compared to healthy controls (HCs). By using the receiver operating characteristic (ROC) curve, we found that a baseline of 2,042 pg/ml plasma Gal-9 can differentiate SARS-CoV-2-infected from noninfected individuals with high specificity/sensitivity (95%). Analysis of 30 cytokines and chemokines detected a positive correlation of the plasma Gal-9 with C-reactive protein (CRP) and proinflammatory cytokines/chemokines such as interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), IP-10, MIP-1α, and MCP-1 but an inverse correlation with transforming growth factor β (TGF-β) in COVID-19 patients. In agreement, we found enhanced production of IL-6 and TNF-α by monocytes and NK cells of COVID-19 patients once treated with the recombinant human Gal-9
MeSH term(s)	Adult ; Age Factors ; Aged ; Aged, 80 and over ; Biomarkers/blood ; COVID-19/blood ; COVID-19/diagnosis ; Cytokine Release Syndrome/blood ; Cytokine Release Syndrome/physiopathology ; Female ; Galectins/blood ; Healthy Volunteers ; Humans ; Male ; Middle Aged ; ROC Curve ; SARS-CoV-2 ; Sex Factors
Chemical Substances	Biomarkers ; Galectins
Language	English
Publishing date	2021-05-04
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2557172-2
ISSN	2150-7511 ; 2161-2129
ISSN (online)	2150-7511
ISSN	2161-2129
DOI	10.1128/mBio.00384-21
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Article ; Online: The Quality of SARS-CoV-2-Specific T Cell Functions Differs in Patients with Mild/Moderate versus Severe Disease, and T Cells Expressing Coinhibitory Receptors Are Highly Activated.

Shahbaz, Shima / Xu, Lai / Sligl, Wendy / Osman, Mohammed / Bozorgmehr, Najmeh / Mashhouri, Siavash / Redmond, Desiree / Perez Rosero, Eliana / Walker, John / Elahi, Shokrollah

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 207, Issue 4, Page(s) 1099–1111

Abstract: Understanding the function of SARS-CoV-2 Ag-specific T cells is crucial for the monitoring of antiviral immunity and vaccine design. Currently, both impaired and robust T cell immunity is described in COVID-19 patients. In this study, we explored and ... ...

Abstract	Understanding the function of SARS-CoV-2 Ag-specific T cells is crucial for the monitoring of antiviral immunity and vaccine design. Currently, both impaired and robust T cell immunity is described in COVID-19 patients. In this study, we explored and compared the effector functions of SARS-CoV-2-reactive T cells expressing coinhibitory receptors and examine the immunogenicity of SARS-CoV-2 S, M, and N peptide pools in regard to specific effector T cell responses, Th1/Th2/Th17, in COVID-19 patients. Analyzing a cohort of 108 COVID-19 patients with mild, moderate, and severe disease, we observed that coinhibitory receptors (e.g., PD-1, CTLA-4, TIM-3, VISTA, CD39, CD160, 2B4, TIGIT, Gal-9, and NKG2A) were upregulated on both CD4
MeSH term(s)	Adult ; Aged ; COVID-19/immunology ; Coronavirus Nucleocapsid Proteins/immunology ; Female ; Humans ; Lymphocyte Activation/immunology ; Male ; Middle Aged ; Phosphoproteins/immunology ; SARS-CoV-2/immunology ; Spike Glycoprotein, Coronavirus/immunology ; T-Lymphocytes/immunology ; Th17 Cells/immunology ; Th2 Cells/immunology ; Viral Matrix Proteins/immunology
Chemical Substances	Coronavirus Nucleocapsid Proteins ; Phosphoproteins ; Spike Glycoprotein, Coronavirus ; Viral Matrix Proteins ; membrane protein, SARS-CoV-2 ; nucleocapsid phosphoprotein, SARS-CoV-2 ; spike protein, SARS-CoV-2
Language	English
Publishing date	2021-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2100446
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Article ; Online: Simultaneous extraction and preconcentration of aniline, phenol, and naphthalene using magnetite-graphene oxide composites before gas chromatography determination.

Nazari, Najmeh / Masrournia, Mahboubeh / Es Haghi, Zarin / Bozorgmehr, MohammadReza

Journal of separation science

2016 Volume 39, Issue 15, Page(s) 3046–3053

Abstract: The coextraction of acidic and basic compounds from different mediums is a significant concept in sample preparation. In this work, simultaneous extraction of acidic, basic, and neutral analytes in a single step was carried out for the first time. This ... ...

Abstract	The coextraction of acidic and basic compounds from different mediums is a significant concept in sample preparation. In this work, simultaneous extraction of acidic, basic, and neutral analytes in a single step was carried out for the first time. This procedure employed the dispersive solid-phase microextraction of analytes with magnetic graphene oxide (graphene oxide/Fe3 O4 ) sorbent followed by gas chromatography with flame ionization detection. After the adsorption of analytes by vortexing and decantation of the supernatant with a magnet, the sorbent was eluted with acetonitrile/methanol (2:1) mixture. The parameters affecting the extraction efficiency were optimized and obtained as follows: sorbent amount 60 mg, desorption time 1 min, extraction time 5 min, pH of the sample 7, sample volume 20 mL, and elution solvent volume 0.3 mL. Under the optimum conditions, linear dynamic ranges were achieved in the range of 0.5-4, 0.25-4, and 0.25-2 μg/mL and limits of detection were 0.341, 0.110, and 0.167 μg/mL for aniline, phenol, and naphthalene, respectively. The relative standard deviations were in the range of 3.3-5.7% in eight repeated extractions. Finally, the applicability of the method was evaluated by the extraction and determination of analytes in stream water and drinking water samples and satisfactory results were obtained.
Language	English
Publishing date	2016-08
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2047990-6
ISSN	1615-9314 ; 1615-9306
ISSN (online)	1615-9314
ISSN	1615-9306
DOI	10.1002/jssc.201600320
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