Publications by authors named "Sayeh Abdossamadi"

9 Publications

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"Age Related Differences in the Biology of Chronic Graft-Versus-Host Disease After Hematopoietic Stem Cell Transplantation".

Front Immunol 2020 16;11:571884. Epub 2020 Oct 16.

Michael Cuccione Childhood Cancer Research Program, British Columbia Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

It is established that pediatric hematopoietic stem cell transplant (HSCT) recipients have a lower rate of chronic graft-versus-host disease (cGvHD) compared to adults. Our group has previously published immune profiles changes associated with cGvHD of clinically well-defined adult and pediatric HSCT cohorts. Since all analyses were performed by the same research group and analyzed using identical methodology, we first compared our previous immune profile analyses between adults and children. We then performed additional analyses comparing the T cell populations across age groups, and a sub-analysis of the impact of the estimated pubertal status at time of HSCT in our pediatric cohort. In all analyses, we corrected for clinical covariates including total body irradiation and time of onset of cGvHD. Three consistent findings were seen in both children and adults, including elevations of ST2 and naive helper T (Th) cells and depression of NK cells. However, significant differences exist between children and adults in certain cytokines, B cell, and T populations. In children, we saw a broad suppression of newly formed B (NF-B) cells, whereas adults exhibited an increase in T1-CD21 B cells and a decrease in T1-CD24CD38 B cells. Prepubertal children had elevations of aminopeptidase N (sCD13) and ICAM-1. T abnormalities in children appeared to be primarily in memory T cells, whereas in adults the abnormalities were in naïve T cells. In adults, the loss of PD1 expression in naïve T and naïve Th cells was associated with cGvHD. We discuss the possible mechanisms for these age-related differences, and how they might theoretically impact on different therapeutic approaches to cGvHD between children and adults.
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http://dx.doi.org/10.3389/fimmu.2020.571884DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7641628PMC
October 2020

Immune profile differences between chronic GVHD and late acute GVHD: results of the ABLE/PBMTC 1202 studies.

Blood 2020 04;135(15):1287-1298

CancerCare Manitoba, University of Manitoba, Winnipeg, MB, Canada.

Human graft-versus-host disease (GVHD) biology beyond 3 months after hematopoietic stem cell transplantation (HSCT) is complex. The Applied Biomarker in Late Effects of Childhood Cancer study (ABLE/PBMTC1202, NCT02067832) evaluated the immune profiles in chronic GVHD (cGVHD) and late acute GVHD (L-aGVHD). Peripheral blood immune cell and plasma markers were analyzed at day 100 post-HSCT and correlated with GVHD diagnosed according to the National Institutes of Health consensus criteria (NIH-CC) for cGVHD. Of 302 children enrolled, 241 were evaluable as L-aGVHD, cGVHD, active L-aGVHD or cGVHD, and no cGVHD/L-aGVHD. Significant marker differences, adjusted for major clinical factors, were defined as meeting all 3 criteria: receiver-operating characteristic area under the curve ≥0.60, P ≤ .05, and effect ratio ≥1.3 or ≤0.75. Patients with only distinctive features but determined as cGVHD by the adjudication committee (non-NIH-CC) had immune profiles similar to NIH-CC. Both cGVHD and L-aGVHD had decreased transitional B cells and increased cytolytic natural killer (NK) cells. cGVHD had additional abnormalities, with increased activated T cells, naive helper T (Th) and cytotoxic T cells, loss of CD56bright regulatory NK cells, and increased ST2 and soluble CD13. Active L-aGVHD before day 114 had additional abnormalities in naive Th, naive regulatory T (Treg) cell populations, and cytokines, and active cGVHD had an increase in PD-1- and a decrease in PD-1+ memory Treg cells. Unsupervised analysis appeared to show a progression of immune abnormalities from no cGVHD/L-aGVHD to L-aGVHD, with the most complex pattern in cGVHD. Comprehensive immune profiling will allow us to better understand how to minimize L-aGVHD and cGVHD. Further confirmation in adult and pediatric cohorts is needed.
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http://dx.doi.org/10.1182/blood.2019003186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7146024PMC
April 2020

A Germline Mutation in the C2 Domain of PLCγ2 Associated with Gain-of-Function Expands the Phenotype for PLCG2-Related Diseases.

J Clin Immunol 2020 02 19;40(2):267-276. Epub 2019 Dec 19.

Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada.

We report three new cases of a germline heterozygous gain-of-function missense (p.(Met1141Lys)) mutation in the C2 domain of phospholipase C gamma 2 (PLCG2) associated with symptoms consistent with previously described auto-inflammation and phospholipase Cγ2 (PLCγ2)-associated antibody deficiency and immune dysregulation (APLAID) syndrome and pediatric common variable immunodeficiency (CVID). Functional evaluation showed platelet hyper-reactivity, increased B cell receptor-triggered calcium influx and ERK phosphorylation. Expression of the altered p.(Met1141Lys) variant in a PLCγ2-knockout DT40 cell line showed clearly enhanced BCR-triggered influx of external calcium when compared to control-transfected cells. Our results further expand the molecular basis of pediatric CVID and phenotypic spectrum of PLCγ2-related defects.
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http://dx.doi.org/10.1007/s10875-019-00731-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086538PMC
February 2020

Anti-Thymocyte Globulin Prophylaxis Induces a Decrease in Naive Th Cells to Inhibit the Onset of Chronic Graft-versus-Host Disease: Results from the Canadian Bone Marrow Transplant Group (CBMTG) 0801 Study.

Biol Blood Marrow Transplant 2020 03 19;26(3):438-444. Epub 2019 Nov 19.

Division of Pediatric Hematology/Oncology/Blood & Marrow Transplant, BC Children's Hospital, Vancouver, British Columbia, Canada; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, British Columbia, Canada. Electronic address:

Anti-thymocyte globulin (ATG) is an established approach to decrease chronic GVHD (cGVHD), yet the exact mechanism is uncertain. To better understand the mechanism of action of ATG in preventing cGVHD, we evaluated the day 100 immune reconstitution of known cGVHD cellular biomarkers using patients from the randomized Canadian Bone Marrow Transplant Group (CBMTG) 0801 trial, which demonstrated a significant impact of ATG on cGVHD. In a separate companion biology study, we evaluated the impact of ATG prophylaxis on cGVHD cellular markers at day 100 in 40 CBMTG 0801 patients. Analysis focused on previously identified cGVHD cellular biomarkers, including naive helper T (Th) cells, recent thymic emigrant (RTE) Th cells, CD21 B cells, CD56 NK cells, and T cells ST2, osteopontin, soluble B-cell activating factor (sBAFF), Interleukin-2 receptor alpha (sCD25), T-cell immunoglobulin and mucin domain-3 (TIM-3), matrix metallopeptidase 3, ICAM-1, C-X-C motif chemokine 10 (CXCL10), and soluble aminopeptidase N. The ATG-treated group had a >10-fold decrease in both RTE naive Th and naive Th cells (P < .0001) and a 10-fold increase in CD56 NK cells (P < .0001). T cells, conventional Th cells, CD21 B cells, and all plasma markers were not affected. In the populations most affected by ATG, changes in naive Th cells were associated with the later development of cGVHD. This analysis suggests that ATG primarily impacts on cGVHD through suppression of naive Th cell expansion after transplantation. These associations need to be validated in additional studies.
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http://dx.doi.org/10.1016/j.bbmt.2019.11.015DOI Listing
March 2020

Comprehensive B Cell Phenotyping Profile for Chronic Graft-versus-Host Disease Diagnosis.

Biol Blood Marrow Transplant 2019 03 14;25(3):451-458. Epub 2018 Nov 14.

Division of Pediatric Hematology/Oncology/Blood and Marrow Transplant, Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, Canada; Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, Vancouver, Canada. Electronic address:

Previous studies have reported single B cell-related chronic graft-versus-host disease diagnostic (cGVHD) biomarkers, such as B cell-activating factor (BAFF), CD21, and immature B cells, but research on the performance of biomarker combinations and the covariate effect of steroids is lacking. The primary objective of this study was to determine the most accurate combination of B cell populations using cell surface staining flow cytometry in an independent cohort of patients with cGVHD. Secondary objectives included assessing the effect of corticosteroid use at sample collection on the makeup and accuracy of the diagnostic panel and identifying the mechanism underlying low surface expression of BAFF receptor (BAFF-R) on B cells in cGVHD. Flow cytometry analysis was performed in an adult cohort of post-HCT patients with cGVHD onset (n = 44) and time-matched recipients without cGVHD (n = 63). We confirmed that the onset of cGVHD was associated with higher soluble BAFF (sBAFF) levels, elevated CD27CD10CD21 CD19 B cell and classical switched memory B cell counts, and reduced transitional and naïve B cell counts. The highest single B cell population area under the receiver operating characteristic (ROC) curve (AUC) was .72 for transitional type 1 CD21 B cells. We also showed a significant inverse relationship between sBAFF and surface BAFF-R expression caused by sBAFF modulation of BAFF-R. Steroid use at sample collection influenced the significance of the sBAFF:B cell ratio, naïve and marginal zone-like B cells. The optimal combination of B cell subsets most significantly associated with cGVHD onset with or without concurrent corticosteroid use resulted in ROC AUCs of .87 and .84, respectively. Transitional and CD21 B cells were the only populations present in both panels; however, analyzing only these populations resulted in ROC AUCs of .79 and .78, respectively. This suggests that the inclusion of other populations and use of different panels depending on steroid use is necessary to achieve better accuracy. sBAFF was not a component of either panel. These novel B cell profiles could be tested prospectively in patients post-HSCT and could lead to focused mechanistic studies.
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http://dx.doi.org/10.1016/j.bbmt.2018.11.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6445755PMC
March 2019

Heterogeneity of chronic graft-versus-host disease biomarkers: association with CXCL10 and CXCR3+ NK cells.

Blood 2016 06 28;127(24):3082-91. Epub 2016 Mar 28.

Michael Cuccione Childhood Cancer Research Program, British Columbia Children's Hospital/University of British Columbia, Vancouver, BC, Canada;

Chronic graft-versus-host disease (cGVHD) remains one of the most significant long-term complications after allogeneic blood and marrow transplantation. Diagnostic biomarkers for cGVHD are needed for early diagnosis and may guide identification of prognostic markers. No cGVHD biomarker has yet been validated for use in clinical practice. We evaluated both previously known markers and performed discovery-based analysis for cGVHD biomarkers in a 2 independent test sets (total of 36 cases ≤1 month from diagnosis and 31 time-matched controls with no cGVHD). On the basis of these results, 11 markers were selected and evaluated in 2 independent replication cohorts (total of 134 cGVHD cases and 154 controls). cGVHD cases and controls were evaluated for several clinical covariates, and their impact on biomarkers was identified by univariate analysis. The 2 replications sets were relatively disparate in the biomarkers they replicated. Only sBAFF and, most consistently, CXCL10 were identified as significant in both replication sets. Other markers identified as significant in only 1 replication set included intercellular adhesion molecule 1 (ICAM-1), anti-LG3, aminopeptidase N, CXCL9, endothelin-1, and gelsolin. Multivariate analysis found that all covariates evaluated affected interpretation of the biomarkers. CXCL10 had an increased significance in combination with anti-LG3 and CXCL9, or inversely with CXCR3(+)CD56(bright) natural killer (NK) cells. There was significant heterogeneity of cGVHD biomarkers in a large comprehensive evaluation of cGVHD biomarkers impacted by several covariates. Only CXCL10 strongly correlated in both replication sets. Future analyses for plasma cGVHD biomarkers will need to be performed on very large patient groups with consideration of multiple covariates.
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http://dx.doi.org/10.1182/blood-2015-09-668251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4911864PMC
June 2016

Insights into the structural stability of nuclear matrix ribonucleoprotein, LMG160: thermodynamic and spectroscopic analysis.

J Biomol Struct Dyn 2014 19;32(6):890-8. Epub 2013 Jun 19.

a Department of Biochemistry, Institute of Biochemistry and Biophysics , University of Tehran , P.O.Box:13145-1384, Tehran , Iran .

Low-mobility group nonhistone chromatin protein, LMG160, is a nuclear matrix ribonucleoprotein particle (RNP) which has a RNA molecule with approximately 300 bases. In this study, structural stability of the intact LMG160 (I-LMG160) was investigated at different ionic strength and in the absence of its RNA moiety (T-LMG160) employing spectroscopic and thermodynamic techniques. The UV absorption spectra showed hypochromicity and red shift under increasing ionic strength for both forms of LMG160 but in different extents. The fluorescence emission intensity was decreased as ionic strength was increased and the Stern-Volmer quenching constant (Ksv) for T-LMG160 was 3.7 times less than for I-LMG160. In the absence of sodium chloride, I-LMG160 exhibited a very stable structure against the temperature change compared to T-LMG160. The thermodynamic parameters showed that the positive values of ΔHm and ΔSm increased by increasing ionic strength in both forms of LMG160. Removal of the RNA moiety altered secondary structure: as T-LMG160 showed more helical content than I-LMG160. From the results, it is concluded that I-LMG160 is more sensitive to alteration of environment and the RNA has an important role in this RNP conformation. Also, interaction of both I- and T-LMG160 with sodium chloride is entropy driven and is usually accompanied by surface hydrophobicity.
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http://dx.doi.org/10.1080/07391102.2013.795872DOI Listing
December 2014

Toxic effects of lead and nickel nitrate on rat liver chromatin components.

J Biochem Mol Toxicol 2011 May-Jun;25(3):127-34. Epub 2010 Nov 15.

Department of Biochemistry, Institute of Biochemistry and Biophysics, University of Tehran, Iran.

The biological activity of heavy metals is related to their physicochemical interaction with biological receptors. In the present study, the effect of low concentrations of nickel nitrate and lead nitrate (<0.3 mM) on rat liver soluble chromatin and histone proteins was examined. The results showed that addition of various concentrations of metals to chromatin solution preceded the chromatin into aggregation and precipitation in a dose-dependant manner; however, the extent of absorbance changes at 260 and 400 nm was different between two metals. Gel electrophoresis of histone proteins and DNA of the supernatants obtained from the metal-treated chromatin and the controls revealed higher affinity of lead nitrate to chromatin compared to nickel nitrate. Also, the binding affinity of lead nitrate to histone proteins free in solution was higher than nickel. On the basis of the results, it is concluded that lead reacts with chromatin components even at very low concentrations and induce chromatin aggregation through histone-DNA cross-links. Whereas, nickel nitrate is less effective on chromatin at low concentrations, suggesting higher toxicity of lead nitrate on chromatin compared to nickel.
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http://dx.doi.org/10.1002/jbt.20368DOI Listing
February 2012

Identification of low-molecular-weight protein (SCP1) from shark cartilage with anti-angiogenesis activity and sequence similarity to parvalbumin.

J Pharm Biomed Anal 2008 Feb 1;46(3):563-7. Epub 2007 Nov 1.

Institute of Biochemistry and Biophysics, Department of Biochemistry, University of Tehran, Tehran, Iran.

Cartilage was considered as a possible natural source of anti-angiogenesis compounds due to its known avascular nature. In this study, a low-molecular-weight protein with an anti-angiogenesis activity was isolated from shark cartilage using a mild extraction procedure. The protein was purified to homogeneity by gel filtration and electroelution techniques and its N-terminal amino acid sequence was determined. The purified protein, designated as SCP1, represented a molecular weight of 13.7 kDa, pI of 6.9-7 and its N-terminal sequence revealed sequence similarity to alpha parvalbumin family. The protein inhibited angiogenesis when subjected to microvessel sprouting of collagen-embedded rat aortic ring assay. It is suggested that SCP1 could be considered as a new angiogenesis inhibitor derived from shark cartilage.
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http://dx.doi.org/10.1016/j.jpba.2007.10.029DOI Listing
February 2008