Elevated levels of circulating monocytic myeloid derived suppressor cells in splenectomised β‐thalassaemia/HbE patients

Siriworadetkun, Sirikwan; Thubthed, Rattanawan; Thiengtavor, Chayada; Paiboonsukwong, Kittiphong; Khuhapinant, Archrob; Fucharoen, Suthat; Pattanapanyasat, Kovit; Vadolas, Jim; Svasti, Saovaros; Chaichompoo, Pornthip

doi:10.1111/bjh.17012

Cited by 6 publications

(9 citation statements)

References 17 publications

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“…Little is known about MDSCs in BTM. Siriworadetkun and colleagues reported an increased level of MO-MDSCs in BTM patients, especially the splenectomized patients, compared to the healthy controls 18 . The chronic in ammation may have triggered bone marrow to generate MDSCs causing MDSC expansion and accumulation in the circulation of BTM patients.…”

Section: Discussionmentioning

confidence: 97%

“…Several studies described a signi cant elevation in total MDSCS and MO-MDSCS cells in chronic in ammatory diseases and tumors 16,17 as an induced core antiin ammatory mechanism to inhibit unwarranted immune cell activities. They negatively regulate immune function by suppressing the activity of T cells, NK cells, and B cells 18 , and their rise in BTM could be implicated in increased liability to infection in this group.…”

Section: Discussionmentioning

confidence: 99%

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Could the Crosstalk Between Mdscs and Tregs Have a Role in β-thalassemia?

Zahran

El‐Badawy

Badawy

et al. 2021

Preprint

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Background: Secondary-iron overload, alloimmunization, and increased risk of infections are common complications in β-thalassemia major (BTM) patients. Tregs and myeloid-derived suppressor cells (MDSCs) play an essential role in preventing excessive immune responses. This research aimed to investigate the interaction between Tregs and MDSCs in BTM patients and their relation with disease severity.Methods: This case-control study included 26 patients with BTM and 23 healthy age- and sex-matched controls. All patients were investigated for complete blood picture, serum ferritin, and flow cytometric analysis of peripheral blood to detect Tregs, MDSCs, and MDSC subsets.Results: A significant increase was observed in the frequencies of Tregs and MDSCs, particularly MO-MDSCs, in the patients compared with the controls. These cells also showed direct relations with ferritin and TLC and an inverse association with hemoglobin. Furthermore, a positive correlation was seen between Tregs and each of the total MDSCs and MO-MDSCs. Conclusion: Our findings highlight the role Tregs and MDSCs cooperatively plays in the BTM and their importance in suppressing the high activity of the immune system found in those patients due to repeated blood transfusions and antigenic stimulation.

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Section: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Could the Crosstalk Between Mdscs and Tregs Have a Role in β-thalassemia?

Zahran

El‐Badawy

Badawy

et al. 2021

Preprint

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“…Only a few studies have described exosomes or microvesicles from hemoglobinopathy adult patients [ 174 , 175 , 176 , 177 , 178 , 179 ]. In addition, most of these studies examined the role of microparticles in circulation from adults with Beta-thalassemia/Hb E disease in relation to the hypercoagulable state.…”

Section: Placenta-derived Evs As Hb Bart’s Liquid Biopsy: Challenges ...mentioning

confidence: 99%

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease

Chaemsaithong

Luewan

Taweevisit

et al. 2023

IJMS

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Extracellular vesicles (EVs) are nano-scaled vesicles released from all cell types into extracellular fluids and specifically contain signature molecules of the original cells and tissues, including the placenta. Placenta-derived EVs can be detected in maternal circulation at as early as six weeks of gestation, and their release can be triggered by the oxygen level and glucose concentration. Placental-associated complications such as preeclampsia, fetal growth restriction, and gestational diabetes have alterations in placenta-derived EVs in maternal plasma, and this can be used as a liquid biopsy for the diagnosis, prediction, and monitoring of such pregnancy complications. Alpha-thalassemia major (“homozygous alpha-thalassemia-1”) or hemoglobin Bart’s disease is the most severe form of thalassemia disease, and this condition is lethal for the fetus. Women with Bart’s hydrops fetalis demonstrate signs of placental hypoxia and placentomegaly, thereby placenta-derived EVs provide an opportunity for a non-invasive liquid biopsy of this lethal condition. In this article, we introduced clinical features and current diagnostic markers of Bart’s hydrops fetalis, extensively summarize the characteristics and biology of placenta-derived EVs, and discuss the challenges and opportunities of placenta-derived EVs as part of diagnostic tests for placental complications focusing on Bart’s hydrop fetalis.

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“…Whole blood samples were lysed with fluorescence-activated cell sorting (FACS) lysing solution (BD Biosciences,) and stained with multi-panels of fluorochrome conjugated monoclonal antibodies specific to characterised immunophenotypes, including neutrophils, monocytes, CD4 + T cells, CD8 + T cells, granulocytic-MDSCs (G-MDSCs) and monocytic-MDSCs (M-MDSCs), as described in previous studies. 4,15,17 Antibodies used in this study are listed in Table S2.…”

Section: Immunophenotyping Of Peripheral Blood White Cellsmentioning

confidence: 99%

“…Moreover, phagocytosis and oxidative burst activity of monocytes from β‐thalassaemia 13 and β‐thalassaemia/HbE patients 4 were observed to be significantly decreased. Recently, we found that splenectomised β‐thalassaemia/HbE patients had increased circulating monocytic myeloid‐derived suppressor cells (MDSCs), which are immune suppressive cells that inhibit T cell proliferation and activation 15 . Impaired neutrophil and monocyte function, together with increased MDSCs could increase the susceptibility to severe infection, which is associated with increased morbidity and mortality in β‐thalassaemia/HbE patients.…”

Section: Introductionmentioning

confidence: 99%

A comprehensive study of immune function and immunophenotyping of white blood cells from β‐thalassaemia/HbE patients on hydroxyurea supports the safety of the drug

et al. 2022

Self Cite

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Hydroxyurea (HU) (hydroxycarbamide) is used as a therapeutic option in βthalassaemia to increase fetal haemoglobin, which results in a reduced requirement for blood transfusion. However, a potential serious adverse effect of HU is neutropenia. Abnormal neutrophil maturation and function in βthalassaemia/HbE patients are well documented. This raises questions about the effect of the drug with regards to the immune response these patients. This study investigated the effects of HU treatment on both innate and adaptive immunity in a cross-sectional study of 28 βthalassaemia/HbE patients who had received HU treatment (BE+HU) as compared with 22 βthalassaemia/HbE patients who had not received HU (BE-HU) and 26 normal subjects. The expression of PU.1 and C/EBPβ, transcription factors, which are associated with neutrophil maturation, was significantly reduced in BE+HU patients as compared with BE-HU patients and normal subjects. Interestingly, C3bR expression on neutrophils and their oxidative burst activity in BE+HU were restored to close to normal levels when compared with BE-HU. There was no observed effect of HU on monocytes, myeloid derived suppressor cells (both granulocytic and monocytic subsets), CD4 + T cells, CD8 + T cells, complement levels and serum immunoglobulin levels in this study. The full immunophenotyping analysis in this study indicates that HU therapy in βthalassaemia/HbE patients does not significantly compromise the immune response.

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Elevated levels of circulating monocytic myeloid derived suppressor cells in splenectomised β‐thalassaemia/HbE patients

Cited by 6 publications

References 17 publications

Could the Crosstalk Between Mdscs and Tregs Have a Role in β-thalassemia?

Could the Crosstalk Between Mdscs and Tregs Have a Role in β-thalassemia?

Placenta-Derived Extracellular Vesicles in Pregnancy Complications and Prospects on a Liquid Biopsy for Hemoglobin Bart’s Disease

A comprehensive study of immune function and immunophenotyping of white blood cells from β‐thalassaemia/HbE patients on hydroxyurea supports the safety of the drug

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