IL-13 R130Q single nucleotide polymorphism in asthmatic Egyptian children

Background: Asthma and its associated phenotypes are under a substantial degree of genetic control. The common variant IL-13 gene polymorphism R130Q is reported to be associated with the risk of development of asthma in some populations. Objective: We sought to study the association of IL-13 genetic variant R130Q with bronchial asthma in Egyptian children and its relation to various clinical and laboratory phenotypes of the disease. Methods: IL13 gene polymorphism (R130Q) was detected by PCR amplification followed by sequencing using pure script total DNA in 20 asthmatic patients in acute exacerbation. The results were compared to 20 healthy age and sex matched children. Results: Asthmatic children had significantly higher frequency of distribution of R130Q genotype (50%) than controls (15%). The serum total IgE as percent of high normal for age was significantly higher in asthmatic patients as compared to controls with a mean of 208.77 ±237.06% and 14.21 ± 8.08% respectively. No significant difference was observed in the mean AEC(as a percent of high normal for age) of both groups (80.85 ± 116.4% and 82.50 ± 81.4% respectively). No significant differences were observed between patients with IL-13 polymorphism R130Q and those without such polymorphism as regards family history, relation of exacerbations to upper respiratory tract infections, history of food allergy or asthma grading. Serum total IgE was significantly higher in asthmatics with GA genotype as compared to those with GG genotype with a mean of 373.25 ± 238.11% and 44.28 ± 42.65% respectively. A similar finding was also observed among the control group with a mean of 28.03 ± 9.12% and 11.77 ± 5.00% respectively. Finally a significantly higher AEC was observed in controls with GA as compared to GG genotype with a mean of 250.00 ± 51.96% versus 52.94 ± 36.87% respectively. Conclusion: The common variant IL-13 gene polymorphism R130Q is frequently associated with pediatric asthma. This variant is more active than the wild type in inducing allergic inflammation as reflected by the higher serum total IgE and AEC. Hence, IL-13R130Q may be candidate for future gene therapy targeted at reducing the ill-effects of this polymorphism.Keywords: IL-13R130Q – bronchial asthma - pediatricsEgypt J Pediatr Allergy Immunol 2010;8(1):9-1

CXCR3 renal expression in glomerulonephritis in children: is there a connection with the course of the disease?

Background: Glomerulonephritis (GN) is a common childhood disease that may represent a significant cause of chronic kidney disease at one point of its course. The role of chemokines in glomerulonephritis, has been long anticipated and studied and the possible link between certain chemokines and different renal pathologies, if proved, can pave the road for future use of such markers for early prognosis and possible therapies for this common disease.Objective: in this study, we aimed at detecting CXCR3 in the renal biopsies done for children with glomerulonephritis and to correlate it to the nature of renal pathology and response to therapy.Methods: The glomerular and interstitial expression of CXCR3 in renal biopsies done for 22 patients with glomerulonephritis was studied using immunohistochemical staining. Pathologies already diagnosed in these biopsies were proliferative GN (mesangioproliferative GN, diffuse proliferative GN, focal proliferative GN, IgA nephropathy and crescentic GN) as well as non-proliferative GN (Minimal change disease, focal segmental glomerulosclerosis, membranous nephropathy, diffuse mesangial sclerosis and advanced hypertensive nephrosclerosis). History, clinical findings and laboratory investigations in the initial presentation and at the time of the study were obtained.Results: The degree of glomerular and interstitial CXCR3 expression did not vary with gender, age of presentation, response to steroids, or cumulative doses of steroids. Percentage of strong glomerular CXCR3 expression was much higher in proliferative GN compared to non-proliferative GN although the difference was not statistically significant, percentage of renal dysfunction was more among strong glomerular and mild/moderate interstitial CXCR3 expression with no statistically significant difference from the counterparts.Conclusion: Our study revealed that enhanced CXCR3 renal expression on glomerular and interstitial levels did not affect the response to steroids along the course of the disease and so can probably act as a therapeutic target rather than a prognostic marker.Keywords: glom. CXCR3, int. CXCR3, glomerulonephritis, renal biops

The diagnostic and monitoring value of serum anti-mutated citrullinated vimentin antibodies (anti-MCV) in juvenile rheumatoid arthritis

Background: JRA is currently diagnosed using the American College of Rheumatology (ACR) 1987 revised criteria that are primarily based on clinical parameters. The criteria may be insufficient for the diagnosis of early RA as they are based upon measurements of disease classification predominately featuring manifestations typical of later-stage disease. Measurement of serum anti-mutated citrullinated vimentin antibodies (MCV) has been shown to be a better marker for early adult RA, and it correlates well with the disease activity score (DAS). Objectives: The aim of this work is to evaluate the role of antimutated citrullinated vimentin antibodies (anti-MCV) in the diagnosis, and in monitoring disease activity in juvenile rheumatoid arthritis. Methods: The study included 40 children with JRA fulfilling the American College of Rheumatology criteria for diagnosis of JRA: 4 children with oligoarticular JRA, 12 with polyarticular JRA and 24 children with systemic onset JRA. Fifty healthy children, matching the patients in age and sex served as a control group. The studied children with JRA were subjected to laboratory tests including CBC, ESR, CRP, ANA and rheumatoid factor (RF). Serum samples from both patients and controls were assayed for anti-MCV levels using an ELISA technique. Results: The study showed high mean serum anti-MCV antibodies level in JRA patients when compared to controls (P= 0.00). In addition, there were no significant correlations between anti-MCV antibody levels and parameters of disease activity, namely, number of swollen joints, number of tender joints, ESR and CRP. The receiver operating characteristic (ROC) curve was drawn and it showed that the area under the curve (AUC) was (0.896). At a cutoff level > 17 u/mL, anti-MCV antibodies had diagnostic specificity of 88%, diagnostic sensitivity of 87.5%, negative and positive predictive values of 89.8% and 85.4%, respectively and diagnostic efficacy of 87.8%. We also reported 3/40 of JRA patients to be positive for RF and 2/40 of JRA patients to be positive for ANA. Conclusion: Measurement of serum anti MCV antibody level holds promise as a diagnostic tool in JRA. However, they failed to show a significant efficacy in determining disease activity.Keywords: Juvenile rheumatoid arthritis, MCVEgypt J Pediatr Allergy Immunol 2012;10(2):75-8

High resolution computed tomography and pulmonary function tests in childhood systemic lupus erythematosus and juvenile rheumatoid arthritis

Background: Alveolar and airway injury represent one of the most common features of rheumatological diseases and is believed to have a significant impact on the course of these diseases. Objective: This work aimed at evaluating airway and alveolar involvement in children with systemic lupus erythematosus (SLE) and juvenile rheumatoid arthritis (JRA). Methods: Thirty four children (21 with SLE and 13 with JRA) were assessed by pulmonary function tests (PFTs) namely spirometry and carbon monoxide diffusion capacity (DLCO) in comparison to 10 healthy controls, as well as by plain roentgenography and high resolution computed tomography (HRCT) of the chest. Results: The studied patients had significantly lower mean PFT values as compared to controls. A restrictive pattern of PFTs was more common as it was detected in 62% of patients with SLE and 23% of those with JRA whereas an obstructive pattern was detected in 14% and 8% respectively. Significantly lower FEF 25-75% values were detected in symptomatic patients. Low values of DLCO (less than 80% of predicted) were recorded in 60% of the studied patients. Chest HRCT was abnormal in 68% of studied patients. In SLE, ground glass appearance and pleural irregularity were the most common findings whereas in JRA, bronchial wall thickening, mosaic appearance and air trapping were prominent. Abnormal findings were detected in 5/9 of asymptomatic patients. Conclusion: airway and alveolar abnormalities are frequently encountered in children with SLE (95%) and JRA (85%) even if they are asymptomatic. HRCT and pulmonary function tests including diffusion studies are recommended as useful tools for the diagnosis and early detection of pulmonary involvement in these patients.Keywords: JRA, SLE, HRCT, PFTs, DLCOEgypt J Pediatr Allergy Immunol 2004; 2(1): 8-1

CXCR 3 expression on CD4+T cells and in renal tissue of pediatric systemic lupus erythematosus patients

Background: Pediatric systemic lupus erythematosus (pSLE) accounts for about 20% of all cases of Systemic Lupus Erythematosus (SLE), with nephritis occurring in approximately 50% of the patients. Objective: to evaluate the expression of CXCR3 in the kidneys and on CD4+ T cells in pSLE. Methods: This study was conducted on 45 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University and 45 age and sex matched healthy children as a control group. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients, the frequency of CXCR3, CD4+ T cells was determined in all patients and controls. Twenty-five Paraffin blocks of patients with lupus nephritis (LN) (available at the time of the study) underwent immunohistochemistry staining for the frequencies of Chemokine C receptor (CXCR3). Results: The absolute level and percentage of serum CD4+CXCR3+ were significantly lower among our patients as compared to healthy controls. A significant direct correlation was found between serum CD4+CXCR3+ and both the lymphocytic count and quantitative Systemic Lupus erythematosus disease activity index (SLEDAI), as well as a significant inverse correlation between it and 24 hours urinary proteins. Variable degrees of CXCR3expression seemed to have no impact on laboratory tests, British Isles Lupus Assessment Group (BILAG) score and cumulative doses of Immunosuppressives. Conclusion: Serum CD4+CXCR3+ and not renal CXCR3 may be a potential marker of LN activity

Membrane endothelial protein C receptor expression in renal tissue of pediatric lupus nephritis patients

Background: Lupus nephritis (LN) is more common and more severe is pediatric systemic lupus erythematosus (pSLE). Endothelial protein C receptor (EPCR) is an inducer of anti-apoptotic pathways in endothelial cells. Recent studies have taken elevated anti-injury biomarkers as EPCR into consideration regarding their roles to antagonize LN.Objectives: to evaluate the membrane expression of endothelial protein C receptor (mEPCR) in the renal microvasculature in pediatric patients with LN.Methods: This study was conducted on 25 patients with pSLE following up at the Allergy and Immunology Clinic, Children’s Hospital, Ain Shams University. The 25 patients have LN proved by a previous renal biopsy. Medical history, clinical examination and routine laboratory investigations for assessment of disease activity were done for all patients. Paraffin blocks of patients’ renal biopsies were subjected to immunohistochemistry staining for the frequency of mEPCR.Results: mEPCR was mainly expressed in the endothelium of the peritubular capillaries. Our results showed that an equal number of patients had nil and mild marker expression (8 patients each, 32%) while 9 patients (36%) showed moderate/strong marker expression. We found that 9 out of 10 (90%) of patients with class II had nil/mild marker expression, 5 patients out of 9 (55.5%) with class III had mild/moderate marker expression, while 5 patients 0ut of 6 (83.3%) with class IV and V had moderate/strong marker expression. We only found a significant statistical difference between the different degrees of mEPCR expression regarding 24 hours urinary proteins. No statistical significance was found between the different degrees of mEPCR expression and different immuno-suppressive therapy dose/kg or renal outcome using the renal British Isles Lupus Assessment Group (BILAG) score; in spite that most of the patients who got improved had nil/mild marker expression.Conclusion: mEPCR -bearing a statistically significant difference in relation to different LN classes- showed more expression in the more aggressive classes; a finding which might suggest a contribution of the endothelium of the renal parenchyma to the pathophysiology of more progressive LN. Hence the tissue marker might emerge as a potential new therapeutic target in the search for more selective treatment for SLE.Keywords: p SLE, mEPCR, renal biopsy, immunohistochemistry, BILAG, lupus nephriti

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century