Evaluation of regulatory T cells frequency and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody; correlation with serum ferritin and folate levels

Shokrgozar, Negin; Amirian, Niloofar; Ranjbaran, Reza; Bazrafshan, Asghar; Sharifzadeh, Sedigheh

doi:10.1007/s00277-020-03931-9

Cited by 15 publications

(11 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In line, the administration of iron isomaltoside had consistent yet not significant effects on effector/ memory tumor infiltrating lymphocyte populations. In contrast, numbers of FoxP3 + CD4 + Tregs were comparable across treatment arms suggesting that the adverse effects of iron towards effector T cell populations where direct rather than indirect and Treg-mediated (72,73).…”

Section: Discussionmentioning

confidence: 92%

Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function

et al. 2020

View full text Add to dashboard Cite

Iron is both, an essential compound for many metabolic processes, and iron deficiency can impact on the proliferation of cells including lymphocytes but also tumor cells. On the other hand, excess iron-catalyzed radical formation can induce cellular toxicity which has been previously demonstrated for T cells in hereditary iron overload. Despite these interconnections, little is known on the effects of clinically approved intravenous iron supplements for curing cancer-related anemia, on T cell differentiation, tumor proliferation, anti-tumor T cell responses and, of clinical importance, on efficacy of cancer immunotherapies. Herein, we analyzed the effects of intravenous iron supplementation on T cell function and on the effectiveness of anti-cancer chemotherapy with IL-2/doxorubicin or immunotherapy with checkpoint-inhibitor anti-PD-L1 in C57Bl/6N female mice with implanted E0771 mammary carcinomas. We found that iron application resulted to an increased availability of iron in the tumor microenvironment and stimulation of tumor growth. In parallel, iron application inhibited the activation, expansion and survival of cytotoxic CD8+ T cells and of CD4+ T helper cells type 1 and significantly reduced the efficacy of the investigated anti-cancer treatments. Our results indicate that iron administration has a tumor growth promoting effect and impairs anti-cancer responses of tumor infiltrating T lymphocytes along with a reduced efficacy of anti-cancer therapies. Iron supplementation in cancer patients, especially in those treated with immunotherapies in a curative setting, may be thus used cautiously and prospective studies have to clarify the impact of such intervention on the outcome of patients.

show abstract

Section: Discussionmentioning

confidence: 92%

Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Additionally, because there was a 1-year time lag between biomarker and echocardiographic measurements, it is possible that we missed associations that would have been observed had they been measured simultaneously. Previous studies have reported possible associations with GDF-15 and anemia [49][50][51][52][53][54][55] ; however, we did not have detailed information on iron stores or other measures of anemia to fully evaluate this association in the present study. This was an observational study, so we cannot determine causality.…”

Section: Discussionmentioning

confidence: 96%

Associations Between Cardiac Biomarkers and Cardiac Structure and Function in CKD

Stein

Zelnick

Anderson

et al. 2020

Kidney International Reports

View full text Add to dashboard Cite

H F is one of the most common cardiovascular complications for persons with CKD, 1 and lower estimated glomerular filtration rate (eGFR) has a graded association with HF development. The pathophysiology of HF is complex in CKD and involves multiple pathways, including inflammation, neurohormonal responses, metabolic and nutritional changes, hemodynamics and fluid status, acid-base changes, and anemia. 2,3 Structural and functional cardiac changes can be appreciated on echocardiography 4 and may precede the development of clinical HF in persons with CKD. Echocardiographic parameters of left ventricular (LV)

show abstract

“…Furthermore, regulatory B cells (CD19 + CD38 hi CD24 hi ) are significantly increased in β–thalassemia major patients, both with and without alloimmunisation, compared with healthy controls 22 . The numbers of regulatory T cells, which have an important role in regulation of immune responses, are also increased in β–thalassemia major, both with and without alloimmunisation, compared with healthy controls 23 . The levels of IL‐6, IL‐10 and transforming growth factor beta (TGF‐β) are higher in transfusion‐dependent thalassemia (TDT) compared with non‐transfusion dependent thalassemia (NTDT) 24 .…”

Section: Discussionmentioning

confidence: 97%

High B‐cell activating factor levels in multi‐transfused thalassemia patients

Watanaboonyongcharoen

Akkawat

Tohthong

et al. 2021

Transfusion Medicine

View full text Add to dashboard Cite

Objectives To assess the associations between B‐cell activating factor (BAFF) and alloimmunisation in multi‐transfused thalassemia. Background Red blood cell (RBC) alloimmunisation is a complication of multi‐transfused thalassemia. BAFF is promoting B cells that produce alloantibodies. Methods/Materials Multi‐transfused thalassemia, 15 years or older, were recruited in the cohort study. Alloantibodies and BAFF levels were analysed. Results Of 114 patients, the overall prevalence of RBC alloimmunisation was 29.8%. The most common alloantibodies were anti‐E, anti‐Mia and anti‐c. BAFF levels were different among the three groups; the patients with baseline alloantibodies (median ± interquartile range 1251 ± 474 pg/ml), without alloantibodies (1098 ± 453) and healthy controls (719 ± 306), p < 0.001. The BAFF level was elevated in the >25 years old patients (vs. the <25, p = 0.011) and the buffy‐coat‐reduced blood recipients (vs. the pre‐storage leukocyte‐depletion, p = 0.005). Absolute lymphocyte count was higher in the patients without baseline alloantibodies (vs. with baseline alloantibodies, p = 0.049) and the splenectomised patients (vs. the non‐splenectomised patients, p < 0.001). Of the 72 patients without baseline antibodies, four who developed new antibodies showed no statistically different BAFF levels compared with those without new antibodies after 40‐month follow‐up (1296 ± 734 vs. 1062 ± 460, p = 0.491). In multivariate analysis, BAFF to absolute lymphocyte ratio was independently associated with RBC alloimmunisation (odds ratio 3.07, 95% confidence interval 1.124–8.369, p = 0.029). Conclusion B‐cell activating factor (BAFF) levels were elevated in multi‐transfused thalassemia and the BAFF to absolute lymphocyte ratio was associated with red blood cell (RBC) alloimmunisation.

show abstract

Evaluation of regulatory T cells frequency and FoxP3/GDF-15 gene expression in β-thalassemia major patients with and without alloantibody; correlation with serum ferritin and folate levels

Cited by 15 publications

References 36 publications

Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function

Iron Supplementation Interferes With Immune Therapy of Murine Mammary Carcinoma by Inhibiting Anti-Tumor T Cell Function

Associations Between Cardiac Biomarkers and Cardiac Structure and Function in CKD

High B‐cell activating factor levels in multi‐transfused thalassemia patients

Contact Info

Product

Resources

About