Interferon-Induced Transmembrane Protein-3 Rs12252-G Variant Increases COVID-19 Mortality Potential in Egyptian Population.

Coronavirus disease 2019 (COVID-19) represented an international health risk. Variants of the interferon-induced transmembrane protein-3 (IFITM3) gene can increase the risk of developing severe viral infections. This cross-sectional study investigated the association between IFITM3 rs12252A>G single nucleotide polymorphism (SNP) and COVID-19 severity and mortality in 100 Egyptian patients. All participants were subjected to serum interleukin-6 (IL-6) determination by ELISA and IFITM3 rs12252 genotyping by real-time polymerase chain reaction. Of all participants, 85.0% had the IFITM3 rs12252 homozygous AA genotype, whereas 15.0% had the heterozygous AG genotype. None of our participants had the homozygous GG genotype. The IFITM3 rs12252A allele was found in 92.5% and the G allele in only 7.5%. There was no significant association (p > 0.05) between the IFITM3 rs12252 SNP and COVID-19 severity, intensive care unit (ICU) admission, or IL-6 serum levels. The heterozygous AG genotype frequency showed a significant increase among participants who died (32.0%) compared with those who had been cured (9.3%). The mutant G allele was associated with patients' death. Its frequency among cured participants was 8.5%, whereas in those who died was 24.2% (p = 0.024) with 3.429 odds ratio [95% confidence interval: 1.1-10.4]. In conclusion, this study revealed a significant association between the G allele variant of IFITM3 rs12252 and COVID-19 mortality. However, results were unable to establish a significant link between rs12252 polymorphism, disease severity, ICU admission, or serum IL-6 levels.

Up-regulated serum levels of interleukin (IL)-17A and IL-22 in Egyptian pediatric patients with COVID-19 and MIS-C: Relation to the disease outcome.

Both IL-17A and IL-22 share cellular sources and signaling pathways. They have synergistic action on epithelial cells to stimulate their production of antimicrobial peptides which are protective against infections. However, both interleukins may contribute to ARDS pathology if their production is not controlled. This study aimed to investigate serum levels of IL-17A and IL-22 in relation to the disease outcome in patients with SARS-CoV-2. Serum IL-17A and IL-22 were measured by ELISA in 40 patients with SARS-CoV-2, aged between 2 months and 16 years, (18 had COVID-19 and 22 had multisystem inflammatory syndrome in children "MIS-C") in comparison to 48 age- and sex-matched healthy control children. Patients with COVID-19 and MIS-C had significantly higher serum IL-17A and IL-22 levels than healthy control children (P < 0.001). Increased serum IL-17A and IL-22 levels were found in all patients. Elevated CRP and serum ferritin levels were found in 90% of these patients. Lymphopenia, neutrophilia, neutropenia, thrombocytopenia and elevated ALT, LDH and D-dimer were found in 45%, 42.5 %, 2.5%, 30%, 32.5%, 82.5%, and 65%, respectively of these patients. There were non-significant differences between patients who recovered and those who died or had a residual illness in serum levels of IL-17A, IL-22 and the routine inflammatory markers of COVID-19. In conclusions, serum IL-17A and IL-22 levels were up-regulated in all patients with COVID-19 and MIS-C. Levels of serum IL-17A, IL-22 and the routine inflammatory markers of COVID-19 were not correlated with the disease outcome. Our conclusions are limited by the sample size.

Up-regulated serum levels of soluble CD25 and soluble CD163 in pediatric patients with SARS-CoV-2.

Similar to hemophagocytic lymphohistiocytosis (HLH), some patients with SARS-CoV-2 have cytokine storm. Serum soluble interleukin-2 receptor (sCD25) and soluble CD163 (sCD163) are potential diagnostic biomarkers for HLH that help in guiding its treatment. This study was the first to investigate serum sCD25 and sCD163 levels in SARS-CoV-2. Serum sCD25 and sCD163 were measured by ELISA in 29 patients with SARS-CoV-2, aged between 2 months and 16 years (13 had COVID-19 and 16 had multisystem inflammatory syndrome in children (MIS-C)), in comparison to 30 age- and sex-matched healthy control children and 10 patients with HLH. Levels of these markers were re-measured in 21 patients with SARS-CoV-2 who were followed up 3 months after recovery. Patients with SARS-CoV-2 had significantly higher serum sCD25 and sCD163 than healthy control children (P < 0.001). SARS-CoV-2 patients had significantly higher sCD25 than patients with HLH (P < 0.05). Serum sCD25 was a good differentiating marker between patients with SARS-CoV-2 and HLH. Although there was a significant decrease of serum sCD25 and sCD163 of the 21 SARS-CoV-2 patients who were followed up, these levels were still significantly higher than the healthy controls levels (P < 0.001).  Conclusion: Serum sCD25 and sCD163 levels were up-regulated in SARS-CoV-2 patients. Serum sCD25 was a good differentiating marker between SARS-CoV-2 and HLH. This initial report requires further studies, on large scales, to investigate the relationship between SARS-CoV-2 and both sCD25 and sCD163, including the disease severity and outcome. The therapeutic role of sCD25 and sCD163 antagonists should also be studied in SARS-CoV-2 patients. What is Known: • Similar to hemophagocytic lymphohistiocytosis (HLH), some patients with COVID-19 have cytokine storm due to excessive pro-inflammatory host response. • Serum soluble interleukin-2 receptor (sCD25) and soluble CD163 (sCD163) are potential diagnostic biomarkers for HLH. Monitoring of serum sCD25 and sCD163 levels can also help in guiding the treatment. What is New: • Serum sCD25 and sCD163 levels are up-regulated in patients with COVID-19, including patients presenting with multisystem inflammatory syndrome in children (MIS-C). • Serum sCD25 is a good differentiating marker between SARS-CoV-2 and HLH.

Up-regulated serum levels of TAM receptor tyrosine kinases in a group of Egyptian autistic children.

TAM receptor family belongs to receptor tyrosine kinases (TAMRTKs). It includes three receptors; Tyro-3, Axl and Mer. TAMRTKs has a great role in resolution of inflammation due to their role in clearance of apoptotic cells by macrophages. Dysregulated TAM signaling pathways are associated with many autoimmune diseases and chronic inflammatory disorders. Autism may be an autoimmune disease in some patients. This work was the first study that investigated serum levels of the soluble ectodomain shed TAMRTKs in a group of autistic children. Serum levels of TAMRTKs were measured by ELISA in 30 autistic children aged between 3.5 and 11 years and 30 age and sex-matched healthy control children. Serum levels of TAMRTKs were significantly higher in autistic children than healthy control children (P < 0.001). Patients with severe autism had significantly higher serum levels of TAMRTKs than patients with mild to moderate autism (P < 0.01). In addition, there were significant positive correlations between scores of the Childhood Autism Rating Scale (CARS) and serum levels of TAMRTKs in autistic patients, (P < 0.01). In conclusions, serum levels of TAMRTKs were up-regulated in autistic children with significant positive correlations with the degree of the disease severity. This initial report requires further studies to investigate the relationship between TAMRTKs and autism.

Plasma levels of nerve growth factor in Egyptian autistic children: Relation to hyperserotonemia and autoimmunity.

Hyperserotonemia and brain-specific autoantibodies are detected in some autistic children. Nerve growth factor (NGF) stimulates the proliferation of B lymphocytes with production of antibodies and also increases mast cell serotonin release. This work was the first to investigate the relationship between plasma NGF and both hyperserotonemia and the frequency of serum anti-myelin basic protein (anti-MBP) auto-antibodies in 22 autistic children aged between 4 and 12 years and 22 healthy-matched controls. Levels of NGF, serotonin and anti-MBP were significantly higher in autistic children than healthy control children (P < 0.001). There was a significant positive correlation between NGF and serotonin levels in autistic patients (P < 0.01). In contrast, there was a non-significant correlation between NGF and anti-MBP levels (P > 0.05). In conclusions, serum NGF levels were elevated and significantly correlated to hyperserotonemia found in many autistic children.

Serum Phosphorylated Neurofilament Heavy Chain Level in Relapsing Remitting Multiple Sclerosis in Correlation to Disease Activity and Disability.

Multiple sclerosis (MS) is a disease of clinical diagnosis. There is no single specific diagnostic test available, no single clinical feature is sufficient to diagnose MS. Hence the necessity to research the presence of new diagnostic, prognostic markers and markers of activity of the disease. As principal components of the axonal cytoskeleton, Neurofilaments (NFs) are released in the interstitial fluid after axonal injury or degeneration. NFs was detected in the serum or cerebrospinal fluid (CSF) allowing their potential use as biomarkers of neurodegeneration as well as disease activity, progression and to directly assess the efficacy of current and emerging therapies for reducing axonal injury and the likely pathological substrate of progressive neurological decline. Serum biomarker of axonal injury could prove useful as a prognostic or monitoring tool. We aimed to study the relationship between serum Phosphorylated Neurofilament Heavy Chain (pNF-H) level and clinical activity of relapsing-remitting MS (RRMS) and disability measured by EDSS score. The study included 60 patients suffering from RRMS diagnosed according to McDonald's criteria 2010 and 30 healthy controls. After verbal consent, all were subjected to detailed medical history, clinical examination using EDSS score and measurement of serum pNF-H by quantitative ELISA. Results demonstrated a significantly higher serum levels of pNF-H in MS patients than healthy controls; pNF-H was 5.02±3.25 in cases and 0.65±0.2 in controls (P < 0.05), with a calculated sensitivity and specificity of 95% and 100%, respectively, and a positive and negative predictive values of 100% and 90.9%, respectively, at a cut-off level of 1.1ng/dl. Additionally, levels of pNF-H were significantly higher among relapsing than remission groups, with 93.33% and 83.33% calculated sensitivity and specificity, respectively, and a positive and negative predictive values of 84.8 % and 92.6 %, respectively, (at that cut-off level 4 ng/dl). In conclusion, pNF-H is a promising marker of MS disease activity and disability assessment.

Plasma Soluble Urokinase Plasminogen Activator Receptor Levels in Systemic Lupus Erythematosus Patients.

This study aimed to determine whether plasma soluble urokinase plasminogen activator receptor (suPAR) could serve as an activity biomarker in systemic lupus erythematosus (SLE) patients. suPAR levels were assessed in SLE patients, compared to healthy controls and correlated with disease activity. Sixty SLE patients were enrolled with assessment of disease activity using SLE Disease Activity Index (SLEDAI), C3, soluble urokinase plasminogen activator receptor level. Patients were divided according to disease activity into three groups: Patients in remission, mild to moderate activity, and high disease activity. Twenty apparently healthy individuals, age and sex matched, were included as a control group and subjected to routine laboratory tests and soluble urokinase plasminogen activator receptor level. The age range of the patients was 19 - 45 years with a mean of 29.07±6.84. suPAR, ESR and C3, but not CRP showed significant differences (P < 0.001), among SLE patients' subgroups. Plasma suPAR demonstrated higher levels among highly active than mild to moderately active or patients in remission, having higher discriminating ability regarding disease activity in comparison to ESR and C3 levels. It was higher in cases of nephritis. The optimum cut-off level of suPAR was >3.5 ng/ml, diagnostic validity tests for suPAR have shown to be 100% for sensitivity, specificity, positive predictive value and 74.1% for negative predictive value. These findings indicate that suPAR may be one of the valuable indicators of disease activity in SLE.

Serum visfatin, resistin and IL-18 in A group of Egyptian obese diabetic and non diabetic individuals.

Resistin and visfatin have been proposed as playing a role in the pathogenesis of insulin resistance. We assessed the relationship between their serum concentrations and insulin resistance in lean, obese diabetic and obese non-diabetic. We explore their relationship with inflammatory markers and anthropometric parameters in obese patients. We measured serum resistin, visfatin levels in obese diabetic, obese nondiabetic patients and in lean subjects. The concentrations of serum resistin showed significant differences among the three groups. Higher levels of visfatin occurred in obese diabetic and non diabetic compared to lean subjects. Higher levels for HOMA-IR occurred in obese diabetic and non diabetic compared to lean subjects. Resistin correlated positively with insulin, HOMA-IR and with hs-CRP in obese diabetic subjects. Visfatin correlated positively with insulin and HOMA-IR in obese diabetic and non-diabetic subjects. Resistin might be involved in the pathogenesis of diabetes. Additionally, IL-18 might be a predictor of insulin resistance.

The link between some alleles on human leukocyte antigen system and autism in children.

The reason behind the initiation of autoimmunity to brain in some patients with autism is not well understood. There is an association between some autoimmune disorders and specific alleles of human leukocyte antigen (HLA) system. Thus, we examined the frequency of some HLA-DRB1 alleles in 100 autistic children and 100 healthy matched-children by differential hybridization with sequence-specific oligonucleotide probes. The risk of association between acquisition or absence of these alleles and autism and also a history of autoimmune diseases in autistic relatives was studied. Autistic children had significantly higher frequency of HLA-DRB1*11 allele than controls (P<0.001). In contrast, autistic children had significantly lower frequency of HLA-DRB1*03 allele than controls (P<0.001). Acquisition of HLA-DRB1*011 and absence of HLA-DRB1*3 had significant risk for association with autism (odds ratio: 3.21 and 0.17, respectively; 95% CI: 1.65-6.31 and 0.06-0.45, respectively). HLA-DRB1*11 had a significant risk for association with a family history of autoimmunity in autistic children (odds ratio: 5.67; 95% CI: 2.07-16.3). In conclusions, the link of some HLA alleles to autism and to family history of autoimmunity indicates the possible contributing role of these alleles to autoimmunity in some autistic children. Despite a relatively small sample size, we are the first to report a probable protective association of HLA-DRB1*03 allele with autism. It warrants a replication study of a larger sample to validate the HLA-DRB1 genetic association with autism. This is important to determine whether therapeutic modulations of the immune function are legitimate avenues for novel therapy in selected cases of autism.

Peanut sensitization in a group of allergic Egyptian children.

BACKGROUND: There are no published data on peanut sensitization in Egypt and the problem of peanut allergy seems underestimated. We sought to screen for peanut sensitization in a group of atopic Egyptian children in relation to their phenotypic manifestations. METHODS: We consecutively enrolled 100 allergic children; 2-10 years old (mean 6.5 yr). The study measurements included clinical evaluation for site of allergy, possible precipitating factors, consumption of peanuts (starting age and last consumption), duration of breast feeding, current treatment, and family history of allergy as well as skin prick testing with a commercial peanut extract, and serum peanut specific and total IgE estimation. Children who were found sensitized to peanuts were subjected to an open oral peanut challenge test taking all necessary precautions. RESULTS: Seven subjects (7%) were sensitized and three out of six of them had positive oral challenge denoting allergy to peanuts. The sensitization rates did not vary significantly with gender, age, family history of allergy, breast feeding duration, clinical form of allergy, serum total IgE, or absolute eosinophil count. All peanut sensitive subjects had skin with or without respiratory allergy. CONCLUSIONS: Peanut allergy does not seem to be rare in atopic children in Egypt. Skin prick and specific IgE testing are effective screening tools to determine candidates for peanut oral challenging. Wider scale multicenter population-based studies are needed to assess the prevalence of peanut allergy and its clinical correlates in our country.

Umbilical cord blood CD45(+)CD34(+) cells coexpression in preterm and full-term neonates: a pilot study.

OBJECTIVE: Human umbilical cord blood (hUCB) is rich in stem cells. The CD45(+)/CD34(+) coexpression in hUCB is a marker of hemopoietic progenitor cells. The objective of this study is to compare the coexpression of hUCB CD45(+)/CD34(+) cells in preterm (PT) and full-term (FT) neonates. METHODS: We studied the coexpression of hUCB CD45(+)/CD34(+) cells in PT and FT neonates. The study included 25 PT (29-36 weeks gestation) and 25 FT (37-41) neonates delivered at Ain Shams University, Maternity Hospital. Absolute mononuclear layer cord blood CD45(+)/CD34(+) cell count were measured by flow cytometry. Morbidity was assessed for 12 of the studied 25 PT infants, using Morbidity Assessment Index for Newborns score. RESULTS: The absolute CD45(+)/CD34(+) count did not differ between PT and FT infants: Z =  -0.485, p = 0.63. There was no correlation between absolute cell count and GA (r = 0.013, p = 0.9) for all 50 neonates. Mode of delivery did not affect the absolute count in the PT infants: Z  =  -0.6, p  = 0.57. There was no correlation between the degree of morbidity and absolute cell count in PT neonates; r = 0.13, p = 0.69. CONCLUSION: The absolute cell count is not affected by gestational age and did not relate to morbidity scores in the studied PT infants. Further, wide-scale work will be needed to study CD45(+)/CD34(+) count in hUCB in sick PT neonates.

Serum visfatin levels in a group of Egyptian obese individuals.

Adipose tissue is an endocrine organ that secretes many adipokines. Visfatin is a relatively novel adipocytokine predominantly secreted from adipocytes and shows insulin mimetic properties. The aim of the study was to assess visfatin levels as well as its relation to selected anthropometric and biochemical parameters in adult obesity. The study included 46 adult obese subjects with body mass index of 52.9 +/- 9 kg/m2. In addition, the control group included 44 healthy individuals with matched age and sex and with BMI values of 23.1 +/- 1 kg/m2. Anthropometric measures included also the height, weight, waist and hip circumferences. Serum visfatin and fasting insulin were assessed using commercially available enzyme immunoassay kits. The insulin resistance index was estimated using the Homeostasis Model Assessment (HOMA). Other biochemical parameters assessed included fasting blood sugar, total serum cholesterol and triglycerides. Significant higher serum visfatin levels were found in obese subjects compared to controls (P<0.05). In addition, a statistically significant positive correlation was obtained between serum visfatin and each of BMI (P<0.05), waist circumference (P<0.001), hip circumference (P<0.001), as well as HOMA (P<0.05) in obese subjects unlike in control group. In conclusion, the observed visfatin increase in obesity together with its positive correlation to HOMA might be suggestive of a role in glucose homeostasis.

The role of measurement of serum autoantibodies in prediction of pediatric neuropsychiatric systemic lupus erythematosus.

UNLABELLED: Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the most difficult manifestations of lupus to diagnose. Measurement of serum brain antibodies has contributed to early diagnosis and management of NPSLE before development of a debilitating disease. We aimed to assess the value of serum anti-ganglioside M1 antibodies in prediction of NPSLE, in comparison to other antibodies used in routine laboratory diagnosis of NPSLE. In addition, we are the first to study the relationship between these antibodies and cognitive function in lupus patients. Serum anti-ganglioside M1, anti-ribosomal P protein and anti-cardiolipin antibodies were measured in 30 lupus patients without clinical evidence of NPSLE, aged 8-16 years, and 30 healthy matched-subjects. Patients were followed-up clinically by monthly neuropsychiatric evaluation and assessment of cognitive function for 12 months. Twelve patients developed neuropsychiatric manifestations during follow-up. Of those patients, 83.3%, 50% and 16.7% were seropositive for anti-ganglioside M1, anti-ribosomal P and anti-cardiolipin antibodies, respectively at the time of initial evaluation before clinical presentation of NPSLE. There was a significant positive association between anti-ganglioside seropositivity and cognitive dysfunction (P<0.001). In addition, anti-ganglioside seropositivity had a significant risk for association with cognitive dysfunction (odds ratio: 36; 95% CI: 4.3-302.8). CONCLUSIONS: Serum anti-ganglioside M1 antibodies had a higher predictive value for NPSLE than other antibodies used in routine laboratory diagnosis of this disease. Thus, they may be reliable parameters for early diagnosis and management of NPSLE before clinical manifestations ensue. In addition, anti-ganglioside M1 antibodies may play a role in cognitive dysfunction found in some lupus patients.

The link of C4B null allele to autism and to a family history of autoimmunity in Egyptian autistic children.

UNLABELLED: The reason behind the initiation of autoimmunity, which may have a role in autism, is not well understood. There is an association between some autoimmune disorders and complement (C) 4B null allele. We aimed to study the association between C4B null allele and autism. In addition, we are the first to investigate the association between this allele and a family history of autoimmune diseases in autistic children. Therefore, we examined the frequency of C4B null allele, by quantitative real-time PCR, in 80 autistic patients and 80 healthy matched-children. The frequency of C4B null allele was significantly higher in autistic patients (37.5%) than healthy controls (8.75%), P<0.001. The frequency of autoimmune diseases in families of autistic children (40%) was significantly higher than healthy children (10%), P<0.001. In addition, a family history of autoimmunity had a significant risk for association with autism (odds ratio=6, 95%, CI=2.5-14.1). C4B null allele had a significant risk for association with autism (odds ratio=6.26, 95% CI=2.55-15.36) and with a family history of autoimmunity (odds ratio=21, 95% CI=6.5-67.8). CONCLUSIONS: the link of C4B null allele to autism and to a family history of autoimmunity may indicate its possible contributing role to autoimmunity in autism.

Frequency of CD4+CD25high regulatory T cells in the peripheral blood of Egyptian children with autism.

Autoimmunity may have a role in autism, although the origins of autoimmunity in autism are unknown. CD4( +)CD25(high) regulatory T cells play an important role in the establishment of immunological self-tolerance, thereby preventing autoimmunity. The authors are the first to study the frequency of CD4(+)CD25( high) regulatory T cells in the blood of 30 autistic and 30 age- and sex-matched healthy children. Patients with autism had significantly lower frequency of CD4(+)CD25(high) regulatory T cells than healthy children (P < .001). These cells were deficient in 73.3% of children with autism. Autistic patients with allergic manifestations (40%) and those with a family history of autoimmunity (53.3%) had a significantly lower frequency of CD4(+)CD25(high) regulatory T cells than those without (P < .01 and P < .001, respectively). In conclusion, CD4(+)CD25( high) regulatory T cells are deficient in many children with autism. Deficiency of these cells may contribute to autoimmunity in a subgroup of children with autism. Consequently, CD4(+)CD25(high) regulatory T cells could be new potential therapeutic targets in these patients.

Evaluation of androgen receptor gene as a candidate gene in female androgenetic alopecia.

BACKGROUND: Genetic polymorphisms of the androgen receptor (AR) gene have been studied in male androgenetic alopecia (AGA); however, little is known about gene polymorphism and female AGA. AIM: To evaluate the AR gene as a candidate gene for female AGA. METHODS: Thirty premenopausal Egyptian female patients with AGA (mean age, 32.3 +/- 7 years) and 11 age- and sex-matched controls were included. All subjects underwent laboratory and pelvic ultrasound evaluation to exclude other precipitating cause(s) of hair loss. Scalp biopsy was taken and the AR gene was evaluated using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: According to Ludwig's classification, all patients had type II AGA. Statistical analysis showed no statistically significant difference in genotype (chi(2) = 5.513, P > or = 0.05) or allele frequency (chi(2) = 1.312, P > or = 0.05) between patients and controls. There was also no statistically significant difference between the genotype and allele frequency with disease duration. CONCLUSION: In contrast with male AGA, no association was found between type II AGA in Egyptian women and the AR gene. Therefore, the genetic study of this gene does not serve as a biomarker for the identification of women with a predisposition to AGA.