Immune thrombocytopenia (ITP) is an autoimmune disease characterized by low platelet count and increased bleeding risk. The initial event(s) leading to antiplatelet autoimmunity remains unclear. Toll-like receptors (TLRs) are the most well-characterized pattern recognition receptors and are a transmembrane protein coded by the Toll genes family. In addition to their protective role in immunity, it is also becoming clear that TLRs exhibit homeostatic roles. Toll-like receptors play potential roles in the development of disease and its maintenance. The objective of this study is to evaluate the distribution of TLR9 gene C/T (rs352140) polymorphisms and its possible association with clinicopathological finding in Egyptian adult primary ITP. This study was carried out at Internal Medicine Department, Menoufia University Hospital, Egypt, from August 2018 to January 2020. Eighty adults (≥ 18 years) were enrolled in the study; 40 patients with primary ITP and 40 healthy individuals as controls. Identification of the TLR9 C/T (rs352140) polymorphic variant was performed by polymerase chain reaction–restriction fragment length polymorphism. In our study, we excluded any other causes of secondary ITP. Distribution of the TLR9 C/T genotypes did not exhibit significant deviation between patients and controls. There was no significant difference between studied groups as regards allele (C and T) frequency. There was no significant difference regarding TLR9 gene C/T (rs352140) polymorphisms between Egyptian adult with primary ITP and controls. TLR9 gene C/T (rs352140) polymorphisms have no relation to any of the clinicohematological variables in primary ITP in Egyptians.

Background: Chronic inflammation with sustained unregulated immune stimulation in autoimmune rheumatic diseases (ARD) may be a risk factor for developing lymphoproliferative disorders (LPD). Markers of ARD activity as high erythrocyte sedimentation rate or erosive joint diseases and the development of B-symptoms were accounted as risk factors for LPD development. We investigated the association of five inflammatory cytokine genes single nucleotide polymorphisms (SNPs): TNF-α-308G>A; TGF-β1 gene codon 10 T>C and 25 G>C; IL-10 promoter SNPs-1082 A>G,-819T>C, and-592A>C; IL-6-174G>C; and IFN-γ 874 T>A with the risk of LPD development in ARD patients. The study was conducted on 70 patients divided into group I, 25 ARD patients diagnosed as RA (n = 15) and SLE (n = 10) and with no history of malignancy; group II, 25 patients diagnosed with LPD and had no ARD; and group III, 20 patients diagnosed with both diseases: ARD and LPD. Cytokine genotyping was analyzed by PCRsequence-specific primer (PCR-SSP). Results: ARD+LPD patients had significantly higher frequency of TNF-α-308A allele and AA+AG genotype (high TNF-α producers) and IL-10-1082A allele and AA genotype (low IL-10 producers) than ARD patients (p = 0.003, p = 0.024, p = 0.003, p = 0.03, respectively) with a significantly increased risk of LPD development in ARD patients expressing the corresponding alleles and genotypes. No significant differences were detected in the distribution frequency of either TGF-β1, IL-6, or IFN-γ SNPs between groups I and III or any of the studied SNPs between groups II and III. The distribution frequency of IL-10 ATA haplotype was significantly increased in group III as compared to group I (p = 0.037). Conclusion: The significantly increased frequency of the high-TNF-α-and low-IL-10-producing alleles and genotypes in ARD patients may participate in the provision of a proinflammatory milieu that eventually increases the risk of LPD development.

Immune thrombocytopenia (ITP) appears to be a heterogeneous disease. In some patients, autoimmunity may be associated with an inflammatory process, and in other patients, low platelets may interfere with other aspects of the coagulation system. Either may predispose to thrombosis or bleeding. Further investigation of the interactions of platelets, with inflammatory cytokines and endothelial biomarkers, may help us to better understand the disease, and to recognize those patients at risk of bleeding, or conversely thrombosis. The aim of this work is to estimate von Willebrand factor (vWF) and vascular cellular adhesion molecule (V-CAM) serum levels in adult immune thrombocytopenic patients (ITP) and to decipher their possible clinical correlates. Eighty adults (≥ 18 years) were enrolled in the study; naive newly diagnosed 40 patients with primary ITP (according to the ASH 2019) and 40 sex and age-matched healthy controls, all groups are subjected for complete blood count (CBC), liver, and renal function tests, ESR, CRP, V-CAM, and VWF-Ag by enzyme-linked immunosorbent assay (ELISA). There was a highly statistically significant difference between case and control as regards to the mean level of VWF-Ag and V-CAM. vWF and V-CAM could serve as biomarkers for endothelial alterations and should be investigated as a predictor of thrombocytopenic bleeding and tailor patient management accordingly.

Background: Circulating microRNAs are potential biomarkers of diagnostic and prognostic impact in various inflammatory and malignant diseases. Aim: Linking inflammation with malignancy, we studied miRNA-21 in sera of hepatitis-C-virus (HCV) and none hepatitis diffuse large B-cell lymphoma (DLBCL) patients, aiming to identify its differential expression and prognosis in DLBCL with its subtypes; germinal center B-cell (GCB) and activated B-cell-like (ABC) and to evaluate its relation with HCV. Subjects and Methods: MiRNA-21 expression was measured using TaqMan quantitative RT-PCR in sera of 30 newly diagnosed DLBCL patients (HCV positive (n = 10), HCV negative (n = 20)) and 20 controls (HCV positive (n = 10), HCV negative (n = 10)). Results: MiRNA-21 expression was significantly higher in DLBCL patients than in control (p = 0.00). Significant positive correlations between miRNA-21 and LDH, IPI and disease stage were detected (p < 0.05). Significantly higher miRNA-21 was detected in ABC sub-type compared to GCB sub-type (p = 0.00). Higher miRNA-21 was associated with worse response (p = 0.016), 2 years overall (p = 0.017) and progression free survival with statistical significance (p= 0.003). Significantly higher miRNA-21 levels were detected in HCV positive DLBCL patients compared to HCV negative patients (p = 0.00). Higher miRNA-21 levels were detected in HCV positive ABC subtype than GCB subtype (p = 0.05). Significantly higher levels were also detected in HCV positive controls compared to HCV negative controls. Conclusion: Our study shows that miRNA-21 is over expressed in our patients with DLBCL, displaying higher levels in ABC than in GCB subtypes. MiR-NA-21 is associated with poor response to treatment and survival in DLBCL. MiR-NA-21 is a potential marker of necro-inflammation independent of its role in tumorogenesis, showing higher expression in HCV positive DLBCL patients compared to none hepatitis patients.