Sara Ibrahim Taha

House dust mite (HDM) allergy contributes to allergic rhinitis and asthma worldwide. Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment, with immunoglobulin G4 (IgG4) and regulatory T cells (Tregs) mediating immune tolerance. Comparative immunological effects of subcutaneous (SCIT) versus sublingual (SLIT) therapy remain underexplored. To evaluate immunological changes induced by SCIT and SLIT and their association with clinical improvement in HDM-allergic patients. In this prospective cohort, 43 adults with HDM-sensitized allergic patients received SCIT (n = 22) or SLIT (n = 21) for nine months. Clinical outcomes were assessed using the Asthma Control Test (ACT) and Rhinitis Control Assessment Test (RCAT). Serum IgG4 and total IgE were measured by ELISA and electrochemiluminescence, respectively, and CD4⁺CD25⁺FoxP3⁺ Tregs were analyzed by flow cytometry. Responders were defined as patients achieving ≥ 20% improvement in ACT or RCAT. Wilcoxon signed-rank, Mann–Whitney U, and Spearman correlation tests were used. AIT increased IgG4 (320 → 920 ng/mL; p < 0.001) and Tregs (3.4% → 6.3%; p < 0.001), with a non-significant decrease in IgE. Responders had higher IgG4 and Tregs and lower IgE than non-responders. SCIT elicited higher IgG4 levels (median 1035 vs 705 ng/mL) and a trend toward greater Treg expansion compared with SLIT, although clinical improvement was similar between groups. IgG4 correlated with ACT ( p < 0.001) and RCAT (p = 0.002), and Tregs correlated positively with IgG4 (p = 0.003) and inversely with IgE (p = 0.010). Both SCIT and SLIT improve clinical outcomes in HDM-allergic patients via total IgG4 elevation and Treg expansion. SCIT may induce stronger systemic immunological responses, supporting the use of these biomarkers for early monitoring and personalized therapy. These findings should be interpreted within the context of a pilot study with a relatively small sample size.

Aims: Murine studies show a promising effect of high-fiber β-glucan on glycemic control and serum lipids. In addition, β-glucan has recently been found to have strong antioxidant and immunomodulatory effects. Oat flakes are a natural source of β-glucan. However, the effects of oat flakes on glycemic variability, dyslipidemia, and pancreatic duodenum homeobox-1 (PDX-1) levels in type 1 diabetes (T1D) remain unclear. Hence, this study assessed the effect of oat flakes on glycemic variability, dyslipidemia, and PDX-1 among adolescents with T1D. Materials and Methods: Sixty adolescents with T1D were divided into 2 equally matched groups. Group A received oat flakes β-glucan 6 g per day for 3 months in addition to an ordinary diet and insulin regimen. Group B received an ordinary diet and insulin regimen. This was followed by crossing over both arms for another 3 months after a two-week washout period. All participants underwent auxological assessment, continuous glucose monitoring (CGM), hemoglobin A1c (HbA1c), fasting lipids, and PDX-1 measurements at baseline, 3 months, and 6 months. Results: Oat flakes consumption resulted in a significant decrease in the coefficient of variation, HbA1c, serum cholesterol, triglycerides, and LDL-C levels (p < 0.001), with a significant increase in TIR, HDL-C, and PDX-1 levels (p < 0.001). However, all these effects waned after the stoppage of the oat flakes, except for HDL-C. Conclusions: Oat flakes have a favorable outcome on glycemic metrics, lipid profile, and PDX-1 in adolescents with T1D.

The pathogenesis of the coronavirus disease 2019 (COVID-19) involves a complex group of cytokines and is significantly influenced by genetic and epigenetic factors. The current study aims to assess the association of COVID-19 severity and mortality with the relative expression of MicroRNA-155 (miR-155) and its association with serum levels of interleukin (IL)-6, IL-10, and their derived ratio. This pilot case-control study included 75 COVID-19 patients and 25 healthy controls. Serum levels of cytokines were analyzed by enzyme-linked immunosorbent assay (ELISA), and assessment of miR-155 relative expression level was done using quantitative real-time PCR in all participants. We found that IL-6, IL-10, IL-6/IL-10 ratio, and miR-155 expression levels were significantly higher in COVID-19 patients than in healthy controls ( p -values < 0.001). The expression level of miR-155 showed significant differences between all severity categories of COVID-19, reaching its highest levels in the severe group. It was also significantly higher in ICU-admitted patients ( p -value < 0.001) and those who died during their hospital stay ( p -value = 0.001). It showed a significant negative correlation with serum IL-10 ( r =-0.249, p -value = 0.031) and a significant positive correlation with IL-6/IL-10 ratio ( r = 0.234, p -value = 0.043). It was also the only independent risk factor for COVID-19 severity by regression analysis and the best predictor for COVID-19 severity by ROC curve analysis. This study reported elevation of cytokines and miR-155 expression in COVID-19 patients. The level of miR-155 expression was associated with COVID-19 severity, mortality, and ICU admission, indicating its potential utility as a biomarker for monitoring the progression of COVID-19 and guiding patient follow-up.

Background: Previous studies have demonstrated that both the hemoglobin glycation index (HGI) and the triglyceride-glucose (TyG) index provide superior measures of glucose metabolism compared to traditional blood glucose markers. Furthermore, genetic variants have been identified as significant contributors to the risk of type 2 diabetes mellitus (T2D) and its related complications, highlighting the interplay between metabolic markers and genetic predisposition. Objectives: The purpose of this study is to assess the value of the TyG index and the HGI as possible indicators of diabetic vascular complications and investigate their association with the HK-1 (rs7072268) polymorphism. Methods: This case-control study included 200 adult participants with T2D and 50 healthy controls. The HGI values were divided into three groups by the tertile method and the TyG index values were divided into two groups by the median level. HK-1 (rs7072268) T>C polymorphism genotyping was done by real-time PCR. Results: This study found that participants with diabetic vascular complications showed significantly higher values of HGI and TyG index than controls and those without vascular complications ( p p <0.001) with higher HGI and TyG index values associated with these genotypes. Conclusions: This study suggests that both the HGI and TyG index are valuable indicators of diabetic vascular complications. Additionally, the HK-1 (rs7072268) TC and TT genotypes were strongly associated with increased risk of diabetes and its vascular complications as well as higher values of HGI and TyG index. These results highlight the potential utility of these markers in predicting diabetic vascular risks.

Acute kidney injury (AKI) has been reported during diabetic ketoacidosis (DKA). Evidence regarding tubulopathy is less established, with its pathophysiology, risk determinants, and short-term outcome to be unraveled. Hence, this study aimed to assess renal tubular functions during DKA, its short-term outcome, and its relation with urinary Netrin-1, DKA severity, and renal perfusion indices. Forty children and adolescents (20 with moderate and 20 with severe DKA) were assessed for urine output (UOP), blood pressure, blood glucose, HbA1c, and urinary Netrin-1, with calculation of serum osmolality and estimated glomerular filtration rate (eGFR). Renal pulsatility and resistivity indices were assessed by renal duplex. Reevaluation was done on days 3 and 14. Sixteen children and adolescents had tubular proteinuria during DKA (40%). Their mean urine output (UOP) during DKA was 14.03 cc/kg/h, and their mean urinary Netrin-1 was 836.9 ng/ml. A significant improvement was observed in the UOP, protein/creatinine ratio, urinary netrin, and serum osmolality after the resolution of DKA accompanied by a significant decrease in renal resistivity and pulsatility indices (p < 0.05). A significant positive correlation was found between tubular proteinuria during DKA and urinary Netrin-1, renal pulsatility, and resistivity indices (p < 0.05). Multivariate regression analysis revealed that serum PH and urinary Netrin-1 were the most significant independent variables associated with tubular proteinuria among children and adolescents during DKA. Conclusion: Transient renal tubulopathy occurs during DKA manifested by tubular proteinuria, polyuria, and hypokalemia; that is correlated with DKA severity, renal perfusion indices, and urinary Netrin-1 and reversible by day 14 post-DKA. Netrin-1 could serve as a potential therapeutic target for DKA-associated tubulopathy. What is Known: •  Diabetic ketoacidosis (DKA) is a severe acute complication of  diabetes mellitus, with negative effect on multiple body organs. •  Studies increasingly suggest acute kidney injury during DKA,  however, data about renal tubular injury during DKA, it's pathophysiology,  risk determinants and short term outcomes are still  unclear. What is New: •  Transient renal tubulopathy was reported in 40 % the studied  children and adolescents during DKA manifested by proteinuria,  polyurea, and hypokalemia. •  This tubulopathy that was correlated with DKA severity, renal  perfusion indices and urinary Netrin-1 and totally reversible by  day 14 post DKA. Graphical Abstract

Cell-free DNA (cfDNA) has emerged as a potential biomarker for assessing disease activity and prognosis in rheumatoid arthritis (RA). However, the association between cfDNA levels and the established RA markers of inflammation and disease severity remains unclear. The current study aimed to detect plasma levels of cfDNA in patients with RA and to investigate their association with RA activity indicators (erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), disease activity score-28 (DAS28)), prognostic markers (rheumatoid factor (RF), anticitrullinated protein antibodies (ACPA)), and the musculoskeletal ultrasonographic (US7) scores. This controlled cross-sectional study included 108 RA patients and 108 healthy controls. Plasma levels of cfDNA were quantified by real-time PCR using ALU repeats. Levels of ESR, CRP, RF, and ACPA were measured using routine laboratory assays. Synovial inflammation and joint damage evaluation was performed using the US7 scoring system. Plasma levels of cfDNA were higher in RA patients than controls ( P < 0.001) and significantly increased with higher DAS28 scores among all RA activity groups. Also, cfDNA levels were significantly positively correlated with ESR, CRP, RF, and ACPA levels ( P-values <0.001). Regarding US7, cfDNA was significantly positively correlated with synovitis and erosion scores ( P-values 0.05). In addition, plasma cfDNA was significantly higher in seropositive RA patients than in seronegative patients ( P = 0.007). The odds ratio for cfDNA as a risk factor for erosions was 2.254. This study revealed that cfDNA levels are elevated in RA patients and positively associated with disease activity indicators and prognosis markers. Further research is warranted to validate these findings in larger cohorts and explore the clinical implications of cfDNA measurement in RA management.

Female obesity is a worldwide health issue linked to chronic metabolic low-grade inflammation (metaflammation) causing multiple obesity-related co-morbid conditions. We aimed to assess the serum levels of wingless integration site family member 5 A (Wnt5a), leptin, and tumor necrosis factor-alpha (TNF-α) as markers of obesity-associated metaflammation and investigate the association with toll-like receptors2 (TLR2) gene (Arg753Gln) single nucleotide polymorphism (SNP) among Egyptian females. The study included 60 females with obesity and 30 matched controls. Serum levels of Wnt5a, leptin, and TNF-α were assessed by ELISA, while TLR2 (Arg753Gln) genotyping was done by PCR-RFLP. Serum Wnt5a, leptin, and TNF-α showed significantly higher levels in females with obesity than controls and a significant increase with higher classes of obesity. They showed significant positive correlations with each other. Only TNF-α and leptin were associated with metabolic syndrome (MetS) among the obesity group. According to TLR2 (Arg753Gln) SNP, the homozygous GG genotype was associated with elevated levels of Wnt5a, leptin, and TNF-α compared to the AA + GA model carriers. No significant differences were found in the distribution of TLR2 Arg753Gln (rs5743708) genotypes and alleles according to obesity or MetS, and the regression analysis showed no significant risk association. Serum Wnt5a, leptin, and TNF-α levels increase in women with obesity and the A allele of TLR2 (Arg753Gln) SNP could be protective against obesity-associated metaflammation.

Some patients with neuromyelitis optica spectrum disorder (NMOSD)-like symptoms test negative for anti-aquaporin-4 (anti-AQP4) antibodies. Among them, a subset has antibodies targeting myelin oligodendrocyte glycoprotein (MOG), a condition now termed MOG antibody-associated disease (MOGAD). MOGAD shares features with NMOSD, like optic neuritis and myelitis, but differs in pathophysiology, clinical presentation, imaging findings, and biomarkers. The present study investigated the prevalence of anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies in anti-AQP4 seronegative Egyptian patients initially diagnosed with NMOSD and the link between their presence and clinical characteristics and disease-induced disability to gain insights into MOGAD. This pilot cross-sectional study included 40 anti-AQP4 antibody-negative patients initially diagnosed with NMOSD, six children and 34 adults. They were screened for anti-MOG antibodies by the indirect immunofluorescence cell-based assay. Of all included patients, only 7.5% (n = 3) were positive for anti-MOG antibodies and had significantly higher disability scores than seronegative patients (p = 0.021). The presence of anti-MOG antibodies was not significantly associated with age (p = 0.696), gender (p = 0.232), type of relapse (p = 0.488), number of attacks (p = 0.968), family history of consanguinity (p = 0.211), family history of autoimmune disease (p = 0.608), nor with smoking (p = 0.608). Detecting anti-MOG antibodies in anti-AQP4-negative NMOSD patients is essential for accurate diagnosis and personalized treatment, as MOGAD is now recognized as a separate clinical entity.