FOXP3 Polymorphism and Susceptibility to Pediatric Acute Lymphocytic Leukemia (ALL): A Preliminary Data

FOXP3 (forkhead box P3) polymorphism is associated with many inflammatory diseases and cancers. Acute lymphoblastic leukemia (ALL) is the most common type of pediatric malignancies.This study was designed to investigate the impact of FOXP3 (-3279C/A and -2383C/T) gene polymorphism on the susceptibility of Egyptian children to ALL. A total of 128 subjects with ALL and 124 healthy controls were enrolled in this study. Genotyping of FOXP3 (-3279C/A and -2383C/T) were performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). There was a significant increase (P<0.01) in FOXP3 (-3279CC) genotype, while FOXP3 -3279CA genotype was significantly decreased in ALL patients compared to controls. Insignificant change in FOXP3 (-2383C/T) genotypes was demonstrated between both groups. FOXP3 (-2383CC) genotype was significantly decreased (p<0.05) in treatment responders compared to non-responders and a significant increased (p<0.05) in relapsed patients comparing to the non-relapsed group. Taken together, our pilot study pointed to the potential role of FOXP3 (-3279C/A) gene polymorphisms in Egyptian children ALL susceptibility. An additional prospective large scale study should be carried out to support our findings

Diagnostic performance and predictive value of rheumatoid factor, anti-cyclic-citrullinated peptide antibodies and HLA-DRB1 locus genes in rheumatoid arthritis

<p>Abstract</p> <p>Background</p> <p>We evaluated the significance of the genes, defined as <it>DRB1*04 </it>or <it>DRB1*01</it>, in rheumatoid arthritis (RA) patients. We focused on the role of genetic and serologic markers to predict disease activity and destructive process of joints.</p> <p>Methods</p> <p>Sixty patients with RA were examined. Radiographic changes were evaluated by (Larsen score) and disease activity was measured by disease activity score 28 (DAS28). The markers analyzed were: erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-cyclic citrullinated peptides (anti-CCP2) and HLA-<it>DRB1 </it>alleles typed by PCR.</p> <p>Results</p> <p>In this study, anti-CCP antibodies, CRP, RF and AKA were detected in 83.3%, 56.7%, 71.7% and 52% of patients respectively. HLA-<it>DRB1</it>*01 was found in 45% of patients and 35% of them had one or two HLA-<it>DRB1*04 </it>alleles. According to <it>DRB1*04 </it>subtypes, (<it>DRB1* 0405</it>) was present in of 80% them. For prediction of grade of activity, the independent predictors were anti-CCP (OR 19.6), and <it>DRB1*04 </it>positive allele (OR 5.1). The combination of <it>DRB1*04 </it>+ anti-CCP antibodies gave increase in the specificity and positive predictive value to 92% and 90 respectively. As regards to the prediction of radiological joint damage, the independent predictors were HLA-<it>DRB1*04</it>, HLA-<it>DRB1*01</it>, RF, and CRP > 18 (OR 5.5, 4.5, 2.5, 2.0 respectively).</p> <p>Conclusion</p> <p>Our findings suggest that anti-CCP2 is superior to RF for the detection of RA and provided predictive information on joint destruction and disease activity. The presence of RA associated antibodies (ACCP or RF) and/or the SE genes are indicative for a poorer radiological outcome and higher grade of activity.</p

Persistence of TEL-AML1 fusion gene as minimal residual disease has no additive prognostic value in CD 10 positive B-acute lymphoblastic leukemia: a FISH study

<p>Abstract</p> <p>Objectives </p> <p>We have analyzed t(12;21)(p13:q22) in an attempt to evaluate the frequency and prognostic significance of <it>TEL-AML1 </it>fusion gene in patients with childhood CD 10 positive B-ALL by fluorescence in situ hybridization (FISH). Also, we have monitored the prognostic value of this gene as a minimal residual disease (MRD).</p> <p>Methods</p> <p>All bone marrow samples of eighty patients diagnosed as CD 10 positive B-ALL in South Egypt Cancer Institute were evaluated by fluorescence in situ hybridization (FISH) for t(12;21) in newly diagnosed cases and after morphological complete remission as a minimal residual disease (MRD). We determined the prognostic significance of <it>TEL-AML1 </it>fusion represented by disease course and survival.</p> <p>Results</p> <p><it>TEL-AML1 </it>fusion gene was positive in (37.5%) in newly diagnosed patients. There was a significant correlation between <it>TEL-AML1 </it>fusion gene both at diagnosis (r = 0.5, P = 0.003) and as a MRD (r = 0.4, P = 0.01) with favorable course. Kaplan-Meier curve for the presence of <it>TEL-AML1 </it>fusion at the diagnosis was associated with a better probability of overall survival (OS); mean survival time was 47 ± 1 month, in contrast to 28 ± 5 month in its absence (P = 0.006). Also, the persistence at <it>TEL-AML1 </it>fusion as a MRD was not significantly associated with a better probability of OS; the mean survival time was 42 ± 2 months in the presence of MRD and it was 40 ± 1 months in its absence. So, persistence of <it>TEL-AML1 </it>fusion as a MRD had no additive prognostic value over its measurement at diagnosis in terms of predicting the probability of OS.</p> <p>Conclusion</p> <p>For most patients, the presence of <it>TEL-AML1 </it>fusion gene at diagnosis suggests a favorable prognosis. The present study suggests that persistence of <it>TEL-AML1 </it>fusion as MRD has no additive prognostic value.</p

Sinopharm&rsquo;s BBIBP-CorV Vaccine and ChAdOx1 nCoV-19 Vaccine Are Associated with a Comparable Immune Response against SARS-CoV-2

Coronavirus disease 2019 (COVID-19) has affected millions of people worldwide. During the early stages of vaccination in Egypt, the ChAdOx1 nCoV-19 and BBIBP-CorV vaccines were the most distributed. The aim of this study was to compare the immune responses and short-term efficacies of these two vaccines. We recruited adults who received two doses of either vaccine. Samples were collected after the first dose of ChAdOx1 nCoV-1 and after the second dose of both vaccines. Antibodies against SARS-CoV-2 antigens were measured using LABScreen&trade; COVID Plus kits, and cell-mediated immune responses were assessed using flow cytometry. Of the 109 recruited subjects, 60 (55%) received the ChAdOx1 nCoV-19 vaccine, and the remainder received the BBIBP-CorV vaccine. The total antibody level did not significantly differ between the two groups. The level of the anti-spike subunit 2 (S2) antibody was significantly higher in the ChAdOx1 nCoV-19 group. The percentages of both total T cells and B cells were unaffected by the type of vaccination. However, the ChAdOx1 nCoV-1 vaccine was significantly associated with a higher percentage of CD8+ cells. The vaccines did not significantly differ in the number or severity of infections postvaccination. None of the participants were admitted to the hospital or died of COVID-19 infection. In conclusion, the BBIBP-CorV vaccine is associated with an immune response and protection against infection that is comparable to that of the ChAdOx1 nCoV-1 vaccine. Follow-up is needed to study the long-term protective effects of both vaccines. Inactivated vaccines are easier to manufacture in developing countries and their limited side effects may lead to better economic benefits by limiting the number of absences from work

Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: is it an Immuno-Inflammatory Disorder?

Background and aims: Portal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients. Material and methods: A total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry. Results: Compared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641-0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each. Conclusion: Enhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results