Neutrophils and monocyte toll like receptors 2 and 4 expression in preterm versus term delivery.

Pregnancy results in an increase in immune cells, especially monocytes, which enhances the innate immune system. The increase of inflammatory cytokines in pregnant women's amniotic fluid, can cause uterine contraction, is linked to preterm labor. These inflammatory responses are controlled by Toll-like receptors (TLRs), which are largely expressed on neutrophils and monocytes. This study aimed to determine the role of neutrophils and monocyte subsets, as well as their expression of TLR-2 and TLR-4 in women with preterm and full-term delivery. The study involved a total of 74 women, comprising of 29 preterm labor, 25 full-term labor, and 20 non-pregnant women. The distribution of three monocyte subsets, namely (CD14++CD16-), (CD14+CD16+), and (CD14-/dim CD16++) was measured. Also, the expression of TLR2 and TLR4 in monocytes and neutrophils was analyzed using flow cytometry. Non-classical monocytes and intermediate monocytes were significantly higher in the preterm group than the control and full-term groups (p=0.041, p=0.043, and p=0.004, p= 0.049, respectively). Women in the preterm group showed significantly TLR2 expression on nonclassical monocytes compared to the control and full-term groups (p=0.002, and p=0.010, respectively). Also, preterm group expression of TLR4 was significantly higher in classical monocytes and nonclassical monocytes in comparison to the control group (p=0.019, and p≤0.0001, respectively). Besides, TLR4 expression was significantly up regulated in the preterm group compared to full-term in non-classical monocyte subset (p < 0.0001). Moreover, the expression of TLR-4 in neutrophils from the preterm group was statistically higher than expression from the full-term labor and control groups (p < .0001 for both). Such findings highlight the important role of monocyte subsets and neutrophils in activating the innate immune system and initiating strong pro-inflammatory responses that induce preterm labor. Additionally, TLR4 and TLR2 expressions on non-classical monocytes may be used as a marker to assess the probability of preterm labor.

Detection and characterization of autoreactive memory stem T-cells in children with acute immune thrombocytopenia.

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by an isolated decrease in platelets below 100 × 109/l after the exclusion of other conditions associated with thrombocytopenia. We investigated the role of different memory T-cell subsets, including T stem cell memory (TSCM), in children diagnosed with primary ITP and its association with therapeutic duration. This case-control study included 39 pediatric patients with acute ITP admitted to the Children's Hospital at Assiut University. Using a FACSCanto flow cytometer, CD8 + and CD4 + T-lymphocytes were gated. Five different subsets were characterized in each of these cells according to CD45RO and CD45RA expression. Afterward, gating was performed based on CCR7, CD95, and CD27. Examination of the CD8 + T cells subpopulation showed that Central memory T (TCM) and CD8+ Naïve T (TN) cells were significantly lower in ITP patients than in healthy children (p < 0.0001) and (p = 0.01), respectively. In addition, CD8 + TEMRA was significantly higher in ITP children than in controls (p = 0.001). CD4 + TCM cells were significantly lower in the ITP patient group (p = 0.04). However, CD4 + TEM was significantly higher in patients than controls (p = 0.04). Our research found that ITP patients had an imbalance in the ratio of CD4+ to CD8+ T cells in the peripheral blood and that TCM cells may be involved in the pathogenetic mechanism of ITP. TCMs could help in prediction of patients with higher risk of developing ITP.

Elevated CD39+T-Regulatory Cells and Reduced Levels of Adenosine Indicate a Role for Tolerogenic Signals in the Progression from Moderate to Severe COVID-19.

Viral infections trigger inflammation by controlling ATP release. CD39 ectoenzymes hydrolyze ATP/ADP to AMP, which is converted by CD73 into anti-inflammatory adenosine (ADO). ADO is an anti-inflammatory and immunosuppressant molecule which can enhance viral persistence and severity. The CD39-CD73-adenosine axis contributes to the immunosuppressive T-reg microenvironment and may affect COVID-19 disease progression. Here, we investigated the link between CD39 expression, mostly on T-regs, and levels of CD73, adenosine, and adenosine receptors with COVID-19 severity and progression. Our study included 73 hospitalized COVID-19 patients, of which 33 were moderately affected and 40 suffered from severe infection. A flow cytometric analysis was used to analyze the frequency of T-regulatory cells (T-regs), CD39+ T-regs, and CD39+CD4+ T-cells. Plasma concentrations of adenosine, IL-10, and TGF-ß were quantified via an ELISA. An RT-qPCR was used to analyze the gene expression of CD73 and adenosine receptors (A1, A2A, A2B, and A3). T-reg cells were higher in COVID-19 patients compared to healthy controls (7.4 ± 0.79 vs. 2.4 ± 0.28; p < 0.0001). Patients also had a higher frequency of the CD39+ T-reg subset. In addition, patients who suffered from a severe form of the disease had higher CD39+ T-regs compared with moderately infected patients. CD39+CD4+ T cells were increased in patients compared to the control group. An analysis of serum adenosine levels showed a marked decrease in their levels in patients, particularly those suffering from severe illness. However, this was paralleled with a marked decline in the expression levels of CD73. IL-10 and TGF-ß levels were higher in COVID-19; in addition, their values were also higher in the severe group. In conclusion, there are distinct immunological alterations in CD39+ lymphocyte subsets and a dysregulation in the adenosine signaling pathway in COVID-19 patients which may contribute to immune dysfunction and disease progression. Understanding these immunological alterations in the different immune cell subsets and adenosine signaling provides valuable insights into the pathogenesis of the disease and may contribute to the development of novel therapeutic approaches targeting specific immune mechanisms.

The dogma of cetuximab in advanced squamous cell carcinoma of the head and neck after failure of surgery and radiotherapy: is it true among patients in upper Egypt?

Background and aim: We aimed from the current study to explore the treatment results of cetuximab in combination with a weekly carboplatin and paclitaxel regimen in advanced squamous cell carcinoma of head and neck (HNSCC) after failure of radiotherapy and chemotherapy. Methods: This study was a non-randomised, single arm, phase 2 efficacy study conducted in two oncology centres in upper Egypt, we recruited 31 patients with recurrent HNSCC previously treated with concurrent chemoradiation ± surgery to receive weekly cetuximab, carboplatin and paclitaxel for 18 weeks followed by maintenance cetuximab every 2 weeks for 12 months. All patients underwent intention to treat analysis. Results: The current study revealed a significant reduction of the size of recurrent primary lesion (p < 0.001), without comparable significant reduction of regional lymph nodes (LNs) (p = 0.06), the current overall response rate (ORR) was 83.9%, ≥1-year progression-free survival (PFS) was 58.1%, also surgical intervention was succeeded to salvage 32.3% who did not achieve complete response to the current protocol, the median PFS was 12 months which was significantly affected by tumour site (p = 0.012), programmed death ligand-1 (PDL-1) expression (p = 0.01) and overall response rate (ORR) (p < 0.001). Conclusion: Based on favourable treatment outcomes, including high ORR and disease control rate, improved median PFS and tolerable toxicity profile, the current weekly cetuximab, carboplatin and paclitaxel with 1 year maintenance cetuximab in responding patients is considered a feasible and effective regimen.