Importance of circulating monocyte subpopulations and Fcγ receptors in immune thrombocytopenia.

Monocytes have been linked to the pathogenesis of immune thrombocytopenia (ITP) because of their role in autoantibody-mediated platelet phagocytosis. However, monocytes constitute unique populations with major differences in expression for surface Fcγ receptors (FcγRs). Thus, we evaluated monocytes in whole blood samples from patients with newly diagnosed and chronic ITP. Monocyte subpopulations were identified phenotypically by flow cytometry and defined according to the surface expression of CD14 (lipopolysaccharide receptor) and of CD16 (low-affinity Fcγ receptor III) into classical (CLM), intermediate (INTM) and nonclassical (non-CLM) monocytes. We also examined the expression of FcγRI/CD64 and FcγRIII/CD16 by monocyte subpopulations. Newly diagnosed patients showed a decrease in non-CLM, expressed as a relative percentage of total monocytes compared with controls and chronic ITP patients. Both non-CLM and INTM of newly diagnosed patients closely correlated with platelet count. These monocyte subpopulations showed significantly enhanced CD64 expression in newly diagnosed patients. On the contrary, patients with chronic ITP presented higher non-CLM in percentage than controls and concomitant lower CLM and total monocytes, in percentage and number. The expression of CD64 was increased by all monocyte subpopulations, CLM, INTM, and non-CLM in chronic patients. In conclusion, differences in monocyte subpopulations, together with enhanced expression of FcγRI/CD64 are evident in patients with ITP.

IL-4Rα (rs1801275) A>G polymorphism in Egyptian immune thrombocytopenia (ITP) patients: a single center experience.

INTRODUCTION: Chronic immune thrombocytopenia (cITP) is characterized by dysregulation of the immune response. Until recently, the role of Th2-related cytokine gene polymorphisms was unclear. Interleukin 4 (IL-4) exerts its functions by binding to three types of IL-4 receptor (IL-4R) complexes. We aimed to explore the potential association between the gene polymorphism of IL-4Rα and cITP. METHODS: We investigated the clinical impact of the IL-4Rα (rs1801275) A>G single nucleotide polymorphism (SNP) using the polymerase chain reaction (PCR) followed by the restriction fragment length polymorphism (RFLP) method in 82 cITP patients and 60 healthy controls (HCs). RESULTS: The IL-4Rα (rs1801275) A>G polymorphism analysis showed the mutant GG genotype was significantly higher in control females (p = 0.033). The wild AA genotype had a higher bleeding score (p = 0.02) in the adulthood onset group. Furthermore, the wild AA genotype in the cITP childhood onset group was significantly associated with the disease severity, as well as the response to treatment (p = 0.040). CONCLUSION: The mutant G allele is protective against the susceptibility to cITP in the Egyptian females. The IL-4Rα (rs1801275) A>G polymorphism may affect the clinical severity of cITP and treatment response in the Egyptian population.

Effect of Interleukin and Hepcidin in Anemia of Chronic Diseases.

BACKGROUND: Anemia of chronic disease (ACD) also termed as the anemia of inflammation has been found to be associated with inflammations, chronic infections, and cancers, particularly in old age. Recent studies revealed that interleukin-6 (IL-6), a proinflammatory cytokine, and hepcidin, an antimicrobial hepatic peptide, play a key role in ACD pathogenesis. Patients and Methods. The study included 40 subjects with chronic diseases and 40 normal subjects of the same age group. Red cell indices, levels of IL-6 and hepcidin, and iron profile were measured in all participants using Bayer ADVIA 120, VITROS 5600, Integrated System/2008, and ELISA assay, respectively. RESULTS: The level of hemoglobin was considerably less in patients of chronic diseases referred to as "cases" than the normal subjects or "controls" (8.7 ± 1.5 vs. 13.2 ± 0.9). Red blood corpuscle (RBC) count, hematocrit (HCT) level, serum iron, mean corpuscular hemoglobin concentration (MCHC), and serum total iron-binding capacity (TIBC) were found to be significantly lower in the cases as compared to controls (p < 0.001). Serum IL-6 and hepcidin levels were substantially higher in the cases than in the controls (p < 0.001). Serum IL-6 and hepcidin levels were substantially higher in the cases than in the controls (p < 0.001). Serum IL-6 and hepcidin levels were substantially higher in the cases than in the controls (. CONCLUSION: This study detected a significant increase in serum IL-6 and hepcidin levels in patients with ACD than the controls. These findings offer an insight into the role played by both cytokine and peptide in the pathogenesis of ACD and thus provide a rationale for future use of novel drugs inhibiting their effects on iron metabolism.

Can Biomarkers of Coagulation, Platelet Activation, and Inflammation Predict Venous Thromboembolism in Patients with Haematological Malignancies?

BACKGROUND: The incidence of venous thromboembolism (VTE) in haematological malignancies varies according to the type and grade of the disease and clinical variables, and there is a need to develop a tool to predict the occurrence of VTE in cancer patients at diagnosis to tailor prophylactic anticoagulation use during treatment. OBJECTIVE: To study the incidence of VTE in haematological malignancies and clarify whether vascular and inflammatory biomarkers could be used as predictors of VTE in those patients. METHODS: This was a prospective observational cohort study. Hypercoagulability and inflammatory biomarkers were assayed in a group of 171 patients with haematological malignancies at diagnosis. These markers included (1) coagulation and fibrinolysis activation markers (D-dimer, fibrinogen, antithrombin, plasminogen activator inhibitor 1), (2) endothelial and platelet activation markers (von Willebrand factor and soluble P-selectin), and (3) inflammatory markers (tumour necrosis factor αand interleukin 6). The end point was mortality or symptomatic VTE. RESULTS/CONCLUSION: The incidence of symptomatic VTE was 7%. None of the tested biomarkers showed statistical significance as predictors for the occurrence of VTE in haematological malignancies. However, there were statistically significant associations between the occurrence of VTE and central venous access device insertion, the prothrombin time, and the erythrocyte sedimentation rate. An ESR above 106.5 mm/h is associated with increased VTE occurrence.