No abstract

BackgroundProduction of immunosuppressive enzymes such as indoleamine 2,3-dioxygenase (IDO) is one of the strategies employed by hematologic malignancies, including acute myeloid leukemia (AML), to circumvent immune surveillance. Moreover, IDO has the ability to convert CD4+CD25− conventional T cells into regulatory T cells (Tregs). In this study, we evaluated the expression of IDO in cytogenetically normal acute myeloid leukemia (CN-AML) patients and its correlation with the Treg marker, FOXP3, as well as clinical and laboratory parameters.MethodsThirty-seven newly diagnosed CN-AML patients were enrolled in our study along with 22 healthy individuals. The expression of the IDO and FOXP3 genes was analyzed by SYBR Green real-time PCR.ResultsBoth IDO and FOXP3 were highly upregulated in CN-AML patients compared to control groups (P=0.004 and P=0.031, respectively). A positive correlation was observed between IDO and FOXP3 expression among AML patients (r=0.512, P=0.001). Expression of IDO and FOXP3 showed no significant correlation with laboratory parameters such as white blood cell and platelet counts, hemoglobin levels, bone marrow blast percentage, gender, and FLT3 mutation status (P>0.05).ConclusionHigher IDO expression in CN-AML patients may be associated with an increased Treg phenotype which may promote disease progression and lead to poor prognosis of CN-AML patients.

Background: Selective IgA deficiency (SIgAD) is the most common primary immunodeficiency disorder, which is characterized by significantly decreased serum levels of IgA. Abnormalities of CD4+CD25^highforkhead box P3 (FoxP3)+ regulatory T cells (T_reg) have been shown in association with autoimmune and inflammatory disorders. Methods: In order to evaluate the relationship between autoimmunity and T_reg in SIgAD, we studied 26 IgA-deficient patients (aged 4–17 years) with serum IgA levels <7 mg/dl, 26 age- and sex-matched healthy controls and 26 age- and sex matched idiopathic thrombocytopenic purpura cases with normal immune system. T_reg were determined by flow cytometry using T_reg markers, including CD4, CD25 and FoxP3. Results: The mean percentage of CD4, CD25+FoxP3+ T_reg from all CD4+ cells was 4.08 ± 0.86 in healthy controls, which was significantly higher than in SIgAD patients (2.93 ± 1.3; p = 0.003). We set a cutoff point (2.36%) for T_reg, which was two standard deviations lower than the mean of normal controls. According to this cutoff point and in order to assess the role of T_reg in clinical SIgAD manifestation, we classified patients into two groups: 16 patients in G1 with T_reg <2.36% and 10 patients in G2 with T_reg >2.36%. Autoimmunity was recorded in 9 patients (53.3%) of G1 and only 1 patient of G2, respectively (p = 0.034). Although a defect in class switching recombination was observed in 40% of the patients in G1, none of the G2 patients had such a defect (p = 0.028). Conclusion: This study showed decreased proportions of T_reg in SIgAD patients, particularly in those with signs of chronic inflammation.

Common variable immunodeficiency (CVID) is the most symptomatic primary antibody deficiency associated with recurrent infections and chronic inflammatory diseases as well as autoimmunity. CD4 + CD25+ FOXP3 + regulatory T cells (Tregs) are critical T cell subsets for maintaining self-tolerance and regulation of immune response to antigens thus play a pivotal role in preventing autoimmunity. Thirtyseven CVID patients and 18 age-/sex-matched controls were enrolled. Peripheral blood mononuclear cells (PBMCs) were obtained from both groups, and the percentage of Tregs was calculated using flow cytometry method. The mRNA expression of Tregs' surface markers cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and glucocorticoid-induced tumour necrosis factor receptor (GITR), which are associated with Tregs' inhibitory function, was compared between patients and controls by quantitative real-time PCR TaqMan method. The results revealed that the frequency of Tregs was significantly lower in CVID patients than normal individuals (P < 0.001). In addition, CVID patients with autoimmunity were found to have markedly reduced proportion of Tregs compared to those cases without autoimmune diseases (P = 0.023). A significant difference was seen in factor forkhead box P3 (FOXP3) expression between CVID patients and controls (P < 0.001). The mRNAs of CTLA-4 and GITR genes were expressed at lower levels in CVID patients compared to control group (P = 0.005 and <0.001, respectively). Our findings showed reduced proportion of Tregs in CVID patients together with downregulation of FOXP3 protein and diminished expression of inhibitory Tregs' markers. It could be concluded that all of these changes may be responsible for cellular immune dysregulation observed in these patients especially those with autoimmune manifestation.

The study suggests that combination chelating therapy with deferasirox and deferoxamine can effectively reduce iron burden in β-thalassemia major patients with heavy iron overload without any significant complications.