Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy

Elalfy, Mohsen Saleh; Adly, Amira Abdel Moneam; Ebeid, Fatma Soliman Elsayed; Eissa, Deena Samir; Ismail, Eman Abdel Rahman; Mohammed, Yasser Hassan; Ahmed, Manar Elsayed; Saad, Aya Sayed

doi:10.1007/s12026-018-9010-y

Cited by 11 publications

(16 citation statements)

References 53 publications

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“…Our results showed low frequencies of NK and NKT cells in SCA patients at steady state. In ElAlfy et al's [66] study, they showed that NK cell frequency was higher in all patients with SDC compared with controls, but the difference was not significant. Furthermore, they showed elevated counts of NK cells with higher levels of IFN-γ, so these cells were activated in SCA patients.…”

Section: Discussionmentioning

confidence: 93%

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Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Garcia

Júnior

Soares

et al. 2020

Journal of Immunology Research

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Background. Sickle cell anemia (SCA) is associated with a chronic proinflammatory state characterized by elevated leukocyte count, mortality from severe recurrent infections, and subsequent vasoocclusive complications with leukocyte adhesion to the endothelium and increased plasma levels of inflammatory cytokines. The immune system has a close connection with morbidity in SCA, but further studies are needed to uncover the involvement of innate and adaptive immunities in modulating the SCA physiopathology. We performed measurements of the frequency of innate and adaptive immunity cells, cytokines, chemokines, and growth factors and immunophenotyping of Toll-like receptor and adhesion molecule expression in the blood of SCA patients and healthy donors to evaluate the different profiles of these biomarkers, the relationship among them, and their correlation to laboratory records and death risk. Material and Methods. Immunophenotyping of cells, Toll-like receptors, and adhesion molecules were performed from peripheral blood samples of SCA patients and healthy donors by flow cytometry and cytokine/chemokine/growth factor measurement by the Luminex technique performed from the serum of the same subjects. Results. Cells of adaptive immunity such as IL-12, IL-17, and IL-10 cytokines; IL-8, IP-10, MIP-1α, MIP-1β, and RANTES chemokines; and VEGF, FGF-basic, and GM-CSF growth factors were higher in SCA patients than healthy donors regardless of any laboratorial and clinical condition. However, high death risk appears to have relevant biomarkers. Conclusion. In the SCA pathophysiology at steady state, there is a broad immunological biomarker crosstalk highlighted by TCD4+CD69+ lymphocytes, IL-12 and IL-17 inflammatory and IL-10 regulatory cytokines, MIP-1α, MIP-1β, and IP-10 chemokines, and VEGF growth factor. High expression of TLR2 in monocytes and VLA-4 in TCD8+ lymphocytes and high levels of MIP-1β and RANTES appear to be relevant in high death risk conditions. The high reticulocytosis and high death risk conditions present common correlations, and there seems to be a balance by the Th2 profile.

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Section: Discussionmentioning

confidence: 93%

“…Sickle cell disease (SCD) is associated with alterations in immune phenotypes [66], and we decided to evaluate NK and NKT frequencies on SCA patients at steady state. Recently, ischemia-reperfusion injury (IRI) with resultant white cell activation has been implicated as an additional contributor to the pathophysiology of SCD [67].…”

Section: Discussionmentioning

confidence: 99%

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Garcia

Júnior

Soares

et al. 2020

Journal of Immunology Research

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“…The sample size was relied upon 95% CI with 80% power, using unpaired t-test and assuming a (two-sided) α of 0.05. Based on previous study (El-Alfy et al, 2018) [11], Mean of CD4+ T lymphocytes (%) for SCD patients group was 34.41 while that of healthy control group was 30.0 and SD was 6.1 (of patients or control) with group size ratio of 1/1, the number of participants was 30 for each group.…”

Section: (C) Flow Cytometric Analysismentioning

confidence: 92%

Evaluation of immunological role of Interferon gamma, Interleukin-10 and CD4+ T lymphocytes in pediatric patients with sickle cell disease

Mahmoud

2020

Al-Azhar University Journal of Virus Researches and Studies

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Sickle cell disease (SCD) is a chronic inflammatory disease associated with increased levels of multiple cytokines as interferon gamma (IFN-γ) during vaso-occlusive (VOC) crisis and steady state. Therefore, we aimed to explore the immunological role of serum IFN-γ, interleukin-10 (IL-10) and CD4 + T lymphocytes in children with SCD at steady state and VOC. This study was conducted on 30 children with SCD (15 at steady state and 15 in VOC) and 30 healthy children as controls. Detailed history, complete physical, clinical examination and laboratory investigations as: complete blood count, serum ferritin, IFN-γ, IL-10 and CD4 + T lymphocytes for all patients were recorded. Results: Significant increase in serum IFN-γ in patients with SCD during VOC compared with patients at steady state and controls (P<0.001). Significant increase in serum IL-10 in patients with SCD at steady state compared with those during VOC and controls (P=0.008 and P=0.04 respectively). CD4 + T lymphocyte decreased in patients with SCD during VOC compared with those at steady state and controls (P<0.001). There was a significant positive correlation between serum IFN-ɣ and number of crisis per year (r=0.648, P=0.0001). Serum IFN-γ was increased in patients with history of frequent crisis per year (P=0.001) and decreased in patients under hydroxyurea therapy (P<0.001). IFN-γ was increased in SCD patients. Increased IFN-γ production in SCD suggesting that functionally activated natural killer cells reflecting a host immunological mechanism leading to antigen antibody activation in SCD. Serum IL-10 increased in SCD patients at steady state. CD4 + T lymphocyte decreased in patients during VOC.

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“…Immune recovery post-HCT is crucial to avoid short and longterm infectious complications. Sickle cell disease patients have disease-specific infectious risk secondary to splenic dysfunction, although splenic phagocytic recovery has been reported in post-HCT period in some patients [94]. Infectious complications are increased following both TCD and TCR haplo-HCT secondary to intense immunoablation and subsequent delayed immune reconstitution [16][17][18].…”

Section: Immune Reconstitution Following Haplo-hct For Sickle Cell DImentioning

confidence: 99%

“…The use of cytokines to boost T-cell subsets is being pioneered in allogeneic transplant to address disease relapse and should be developed for non-malignant diseases to improve pathogen-specific immunity and engraftment. The role of natural killer cell killer immunoglobulin-like receptor ligand mismatching is also underexplored in sickle cell disease, though is important given the association between NK cells underlying sickle cell disease pathogenesis [94]. Multi-institution randomized trials comparing TCD and TCR approaches must be performed to truly know which platforms are preferred.…”

Section: Five-year Viewmentioning

confidence: 99%

T-cell deplete versus T-cell replete haploidentical hematopoietic stem cell transplantation for sickle cell disease: where are we?

Patel

Akinsete

Connelly

et al. 2019

Expert Review of Hematology

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Introduction: Severe sickle cell disease is associated with progressive end-organ damage and early mortality in adults. While allogeneic hematopoietic cell transplant from a matched related donor is curative, the vast majority of patients do not have a compatible sibling. Accordingly, platforms using haploidentical donors have been developed, which provide near-universal availability. Areas covered: This review focuses on the two commonly used approaches for haploidentical hematopoietic transplants, namely T-cell deplete and T-cell replete, each of which is associated with unique benefits and drawbacks. The purpose of this paper is to facilitate individualized decision-making for patients and providers by reviewing the pros-and cons of these differing approaches. Expert opinion: Individuals with sickle cell disease eligible for a hematopoietic cell transplant can be considered based on recent results. Comparable outcomes are seen with T-cell deplete and T-cell replete approaches. The choice depends largely on institutional preference.

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Immunological role of CD4+CD28null T lymphocytes, natural killer cells, and interferon-gamma in pediatric patients with sickle cell disease: relation to disease severity and response to therapy

Cited by 11 publications

References 53 publications

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Sickle Cell Anemia Patients Display an Intricate Cellular and Serum Biomarker Network Highlighted by TCD4+CD69+ Lymphocytes, IL-17/MIP-1β, IL-12/VEGF, and IL-10/IP-10 Axis

Evaluation of immunological role of Interferon gamma, Interleukin-10 and CD4+ T lymphocytes in pediatric patients with sickle cell disease

T-cell deplete versus T-cell replete haploidentical hematopoietic stem cell transplantation for sickle cell disease: where are we?

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