Innate-like T cells in children with sickle cell disease

Abstract

Background The implication of lymphocytes in sickle cell disease pathogenesis is supported by a number of recent reports. These studies provided evidence for the activation of invariant natural killer T (iNKT) cells in adult patients, but did not investigate the involvement of other innate-like T cell subsets so far. Methods Here we present a monocentric prospective observational study evaluating the number and functional properties of both circulating conventional and innate-like T cells, namely iNKT, Mucosal-Associated Invariant T (MAIT) and gammadelta (γδ) T cells in a cohort of 39 children with sickle cell disease. Results Relative to age-matched healthy controls, we found that patients had a higher frequency of IL-13- and IL-17-producing CD4 + T cells, as well as higher MAIT cell counts with an increased frequency of IL-17-producing MAIT cells. Patients also presented increased Vδ2 γδ T cell counts, especially during vaso-occlusive crisis, and a lower frequency of IFNγ-producing Vδ2 γδ T cells, except during crisis. iNKT cell counts and the frequency of IFNγ-producing iNKT cells were unchanged compared to controls. Our study revealed positive correlations between 1) the frequency of IFNγ-producing CD4 + , CD8 + and Vδ2 γδ T cells and the number of hospitalizations for vaso-occlusive crisis in the previous year; 2) the frequency of IFNγ-producing iNKT cells and patients’ age and 3) the frequency of IL-17-producing Vδ2 γδ T cells and hemoglobin S level. Conclusion These results strongly suggest a role of innate-like T cells in sickle cell disease pathophysiology, especially that of IL-17-producing MAIT and γδ T cells.

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

“…We found elevated LDH and serum ferritin in SCD patients in VOC and at steady state compared with controls. Allali et al, (2019) showed elevated LDH in SCD at steady state [16] and El-Alfy et al, (2018) demonstrated elevated serum ferritin and LDH in SCD patients at steady sate [11]. On the basis of immunological data, we demonstrated significant increase in IFN-γ in SCD patients in VOC compared with SCD patients at steady state and controls.…”

A Review of the Relationship between the Immune Response, Inflammation, Oxidative Stress, and the Pathogenesis of Sickle Cell Anaemia

“…The innate and adaptive immune responses in SCD are impaired and cannot effectively protect against infection [25,26] with some researchers reporting that the persistent activation of the innate immune system results in the generation of excessive amounts of reactive oxygen species (ROS) (13,(28)(29)(30). According to Ahmad and Ahsan [27], Engwa et al [28] and Atiku et al [10] elevated amounts of reactive species induce oxidative stress and tissue injury, while other reports have revealed that the adaptive immune cells are also dysfunctional, resulting in lower antibody levels compared to healthy individuals [24].…”

Trace Element Levels and Socio-Demography of Pre-Teen Nigerians with Homozygous Sickle Cell Disorder

“…Studies carried out by various teams revealed that by using anthropometric criteria as focus of study, significant stunting of growth was observed among patients of sickle cell disease (SCD) compared with unaffected controls of the same gender, age and socio-economic status. Data obtained from past studies have shown that not only growth retardation but other clinical features such as immunologic and nutritional abnormalities are associated with micro-and macronutrient deficiency among individuals with sickle cell anaemia (SCA) [3][4][5].…”