BACKGROUND:Drug-resistant Tuberculosis (DR-TB) is a global health burden with high morbidity and mortality in developing countries including Egypt. The susceptibility to infection with DR-TB strains may be genetically determined. Several interleukin gene polymorphisms were investigated as risk factors for tuberculosis infection but focusing on their association with DR-TB was limited. Therefore, the objective of this study is to assess the association of IL 17 - 197 G > A (rs2275913) single nucleotide polymorphism (SNP) with susceptibility to DR-TB strains in comparison to drug-sensitive tuberculosis (DS-TB) strains in Egyptian patients with pulmonary TB. This cross-sectional study was conducted on 80 patients with DR-TB strains and 80 with DS-TB strains as a control group. Both age and sex were comparable among the study's groups. IL-17 - 197 G > A (rs2275913) SNP was genotyped by real-time PCR, and IL-17 serum concentration was measured by enzyme-linked immunosorbent assay (ELISA). RESULTS:The GA and AA genotype frequencies of IL 17 - 197 G > A (rs2275913) SNP were significantly higher in patients with DR-TB strains than those with DS-TB strains (p < 0.001). The frequency of the A allele was significantly (p < 0.001) higher in patients with DR-TB group (32.5%) compared to the control group (13.8%). Substantial higher serum levels of IL-17 were detected in the DR-TB group with significant association with AA and AG genotypes. CONCLUSION:Polymorphism in IL-17 -197 G > A (rs2275913) resulted in higher serum levels of IL-17 and Egyptian patients with such polymorphism are three times at risk of infection with DR-TB strains than patients with wild type.

This study intended to explore the relationship between the +869T/C polymorphism of the transforming growth factor-β1 (TGF-β1) gene and rheumatoid arthritis (RA) predisposition and activity in Egyptian patients. The study involved 30 patients suffering from RA and 30 apparently healthy participants as the control group. The +869T/C polymorphism of the TGF-β1 gene was determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) process. The TGF-β1 + 869 CT genotype and CT+TT genotypes in RA patients showed a significant increase than the control group (OR=3.782 and 3.824, CI=1.046-13.680 and 1.150-12.713, P=0.043 and 0.029, respectively). T allele showed a significant increase in patients than in controls (OR= 2.104, CI 1.015- 4.361, P = 0.046). The TGF-β1 +869 CT+TT genotypes were accompanied by higher DAS-28 scores which express higher disease activity, and increased levels of RF, Anti-CCP, ESR, and CRP. In conclusion, the TGF-β1 +869T/C gene polymorphism may be accompanied by an increased predisposition to RA and with its severity in Egyptian RA patients.

Background and Aim Chronic kidney disease (CKD) and its final stage: end-stage renal disease (ESRD), are common clinical conditions. Endocan is a human endothelial cell-specific molecule produced by endothelial cells. Its production is related to activation of endothelium and angiogenesis. In this study, we assessed the relation between serum endocan levels and subclinical atherosclerosis (SCA) in CKD and hemodialysis (HD) patients. Subjects and Methods The present case control study enrolled 30 patients on regular HD for at least 6 months, 30 patients with CKD, and 30 age and sex-matched healthy controls. All participants were subjected to careful history taking and thorough clinical examination. Laboratory investigations included complete blood count, kidney functions, and serum cholesterol, triglycerides, calcium, phosphorus, albumin, PTH, hsCRP, and endocan levels. Results HD and CKD groups had significantly higher endocan levels when compared with control group (median (IQR): 519.0 (202.3–742.0) versus 409.0 (245.3–505.3) and 273.0 (168.0–395.5) ng/L, respectively). Also, HD patients had significantly higher endocan levels when compared with CKD levels. HD patients had significantly higher carotid intima-media thickness (CIMT) when compared with CKD patients (median (IQR): 0.80 (0.80–0.90) versus 0.75 (0.73–0.75) mm, p < 0.001). HD patients had significantly higher frequency of SCA when compared with CKD patients (46.7% versus 13.3%, p=0.005). Patients with SCA had significantly higher hsCRP (median (IQR): 36.5 (26.8–43.5) versus 24.0 (15.8–29.0) mg/dl) and endocan levels (697.0 (528.3–974.8) versus 222.5 (158.8–565.8) ng/L) when compared with patients without SCA. ROC curve analysis of endocan for identification of SCA in HD patients showed that at a cutoff of 380.5 ng/L, endocan has an AUC of 0.862 with a sensitivity and specificity of 92.9% and 68.7%, respectively. Conclusions Serum endocan levels are related to SCA in HD patients. In addition, it is associated with the hyperinflammatory state in those patients.

Introduction Neonatal sepsis can quickly progress to multi-organ failure with high morbidity and mortality, making early diagnosis mandatory. Although being the gold standard, the long duration of blood culture may lead to hazardous neonatal complications. Sepsis activates monocytes and changes their subset distribution with the resultant activation of lymphocytes and adaptive immune cells changing the plasma cytokines levels. Subjects and Method Percentages of monocytes subsets, pattern of monocytes surface CD86 expression and serum IL-17 compared to serum procalcitonin were measured in 30 neonates with early sepsis and compared with age and sex matched 30 apparently health neonates as a control group. Results Gestational age, neonatal weight and hemoglobin concentration were significantly low in septic neonates vs the control group. Percentages of intermediate, nonclassical and CD86 positive monocytes, the mean fluorescence intensity of CD16 on CD16 positive monocytes, and serum levels of CRP, IL-17 and procalcitonin were significantly increased in septic neonates compared with the control group. Conclusion Early neonatal sepsis was associated with increasing the percentage of CD86 positive monocytes. Serum IL-17 levels were positively correlated with increased serum procalcitonin.

Background Obesity is characterized by chronic low-grade inflammatory responses, which may explain the development of obesity-related pathologies, such as insulin resistance and metabolic syndrome (MetS). It is also associated with abnormal levels of cytokines, and osteopontin may be one of them. Aim To assess serum osteopontin level in obese adults with and without MetS and to study its relation to insulin resistance. Patients and methods This comparative study was conducted on 50 obese adults recruited from Endocrinology and Metabolism Department of Al-Zahraa University Hospital. They were divided into two groups according to the presence of MetS. Group 1 included 25 patients without MetS, and group 2 included 25 patients with MetS. Detailed history, clinical examination, and anthropometric measurements were assessed for all selected patients. Fasting plasma glucose, glycosylated hemoglobin (HbA1c), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol, fasting insulin, and osteopontin were measured, and then insulin resistance index (IR) was measured as follows: [INLINE:1] Results TC, TGs, LDL-C, fasting plasma glucose and insulin, HBA1c, and osteopontin were statistically significantly higher in group 2 as compared with group 1. A significant positive correlation was found between osteopontin on one hand and systolic blood pressure, diastolic blood pressure, fasting blood sugar, LDL-C, TC, TG, HbA1c, fasting plasma insulin, and homeostatic model assessment of insulin resistance on the other. No correlation was found between osteopontin and high-density lipoprotein cholesterol. Conclusion Elevated serum osteopontin level is associated with MetS and its different components and thus it may serve as a diagnostic biomarker for MetS.

Background: Hepatitis C Virus (HCV) infection is a progressive disease that may result in chronic hepatitis, fibrosis and cirrhosis.Assessment of liver fibrosis is an essential factor in the management of chronic HCV.Objective: To evaluate plasma soluble Urokinase Plasminogen Activator Receptor (sU-PAR) and interleukin-34 (IL-34) as serological markers of liver fibrosis in patients with chronic HCV.Methods: This case-control study enrolled 60 chronic HCV patients who were subdivided into three groups of mild, moderate and severe hepatic fibrosis depending on Fibrosis-4 score (FIB-4).Patients were compared with 20 age and sex-matched controls.Plasma sUPAR and IL-34 levels were measured by Enzyme Linked Immunosorbent Assay (ELISA).Results: Plasma sUPAR and IL-34 were significantly increased in HCV patients when compared with controls, and their increase was positively correlated with the progression of hepatic fibrosis.Plasma sUPAR and IL-34 positively correlated with Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT), and negatively correlated with hemoglobin concentration and platelet count.The output data of Receiver Operating Characteristic (ROC) curve to differentiate patients from controls revealed that sU-PAR at cut-off > 186.2 ng/L and Area Under Curve (AUC) of 0.944 had (85%) sensitivity and (100%) specificity, and IL-34 at cut off > 16.4 ng/L and AUC of 0.942 had (75%) sensitivity and (100%) specificity.The output data of ROC curve to differentiate severe from mild to moderate hepatic fibrosis patients revealed that sUPAR at cut-off > 510 ng/L and AUC of 0.837 had (80%)

In critically ill patients, acute kidney injury (AKI) is a devastating problem often associated with adverse outcomes. Depending on the conventional markers for diagnosis of AKI, an undesirable delay in the diagnosis and initiation of treatment has occurred. Thus, it is challenging to find a biomarker for early diagnosis of AKI. We sought to evaluate urinary YKL-40 as a biomarker for early diagnosis of AKI among critically ill patients compared with conventional markers and to assess its relation to the severity of AKI. Thirty-six patients without AKI at the time of ICU admission who enrolled in this prospective cohort study had the following measured: serum creatinine as well as urine YKL-40 at admission and thereafter at 4 time intervals (0, 12, and 24 ± 48 h) (therefore, we studied 94 urine samples in 36 patients). Urine YKL-40 was quantified by enzyme-linked immunosorbent assay (ELISA). AKI was defined using the Kidney Disease Improving Global Outcomes (KDIGO) criteria, which include three stages (1, 2, and 3) of progressive renal dysfunction. In this study, 18 (50%) patients developed AKI within 48–72 h. Moreover, urine YKL-40 increased significantly within 12 h in patients who developed AKI (n = 18, 11.75 ± 1.94), but not in non-AKI patients (n = 18, 5.66 ± 3.42) ng/ml (P < 0.001) and, at the same time, we did not find any significant difference in the serum creatinine levels between the two groups. In addition, AKI group showed rising levels with KIDGO classes. In this pilot study we found that urinary YKL-40 can be used as a valuable and noninvasive marker for early diagnosis of AKI among critically ill patients in ICU as compared to conventional markers and its level is increasing with the severity of AKI classes. However, the small sample size is important limitation. Therefore, large multicenter studies may be needed to confirm it.

Background: The implementation of universal hepatitis B virus vaccination programs had led to significant reduction in the incidence of acute and chronic HB infection, liver cirrhosis and hepatocellular carcinoma. However, this success is being threatened by the discovery of HBV vaccine breakthrough infection and vaccine associated non response. Aim: of this cross-sectional study was to evaluate the effectiveness of zero dose HBV vaccine on prevention of HBV breakthrough infection among vaccinated Egyptian infants and to study the role of IL4 SNPs as a cause of vaccine non-responsiveness. Materials and methods: The present study was carried out on 77 infants their age ranged from 6 to 12 months; all of them received HBV vaccine according to the new schedule as the Egyptian Public Health Authority recommend, the first dose was administered within the first 24 hours after delivery. Their serum samples were screened for the presence of HBsAg and HBV-DNA as markers of infectivity. Their HBsAb level was detected to assess their immunity and Cytokine gene analysis to identify IL4 gene polymorphism associated with non-responsiveness to HBV vaccination. Results: It was found that all infants were negative for HBV DNA but HBsAg was positive in 61 out of 77 (79.2%). HBsAg positivity increases after the fourth dose of vaccination and persists for two, four and even six months after vaccination in23.4%, 9.1% & 11.7% of vaccinated infants respectively. There was positive correlation between HBsAg positivity and HBs antibody titer as HBsAg positivity was 60% in non-responders, 77% in low responders and 81% in high responders, there was no statistically significant association between HBsAg positivity and the mode of delivery. The presence of IL4 SNPs especially SNP3 is correlated with the non and low responders to HBV vaccine, however this correlation is statistically non-significant. Conclusion: HBV infection rates have significantly reduced after the introduction of the zero-dose vaccination. The presence and persistence of positive HBsAg with negative HBV- DNA after vaccination may be vaccine induced and not HBV breakthrough infection.

Background: The mechanism of osteoporosis in rheumatoid arthritis (RA) is multifactorial. Autoimmunity and chronic inflammation, among pathogenic factors, are closely related to bone resorption. However, the contribution of B cells to bone resorption in patients with RA is still controversial. Aim: This study aimed to assess the expression of CD19+CD5+ lymphocytes frequency in the peripheral blood of RA patients and their correlation with disease activity, bone resorption and bone density to determine whether this cell has a role in RA and its related bone loss. Subjects and methods: A prospective cross-sectional observational study was carried out on 34 RA patients fulfilling the ACR/EULAR (2010) criteria and 20 healthy age and sex matched healthy controls. Blood was analyzed using flow cytometry to determine the percentage of B lymphocytes expressing cell surface markers CD19+ CD5+. Rheumatoid factor (RF), anti-citrullinated protein antibody (Anti CCP) and bone resorption marker C-terminal telopeptide of type I collagen (CTX-1) were determined from the patients’ sera. Disease activity was assessed by disease activity score (DAS28-ESR) and bone mineral density (BMD) was determines by Dual Energy X-ray Absorptiometry (DEXA). Results: The percentages of circulating CD19+ CD5+ B lymphocytes were significantly higher in RA patients compared to healthy controls (1.60 % Vs 0.90% respectively; P = 0.002) and in RA patients with high activity compared to those with low activity (p=0.013). The percentages of circulating CD19+ CD5+ B lymphocytes in RA patients was positively correlated to ESR (r = 0,449, P = 0.008), DAS28-ESR (r = 0.515, P = 0.002), and RF (r = 0.389, P=0.023) and negatively correlated with BMD at left forearm (r = -0.573, P = 0.000) but not at lumbar spine, total left femur or bone resorption marker (CTX-1) in RA patients. Conclusion: The frequency of CD19+CD5+ B lymphocyte were higher in Egyptian RA patients compared to normal controls and correlates positively with disease activity parameters and inversely with BMD measurement at forearm site but not at lumbar spine, femur or bone resorption marker (CTX-1) in RA patients suggests a possible role of CD19+CD5+B lymphocyte in RA pathogenesis. However, it's weakly associated with RA related bone loss and for better clarification of the role of CD19+CD5+ B lymphocyte on bone mass in RA, larger scale longitudinal are recommended.

Background: Serum cartilage oligomeric matrix protein (COMP) is a non-collagen glycoprotein produced by the cartilage, synovium, tendon, and meniscus. COMP is a reliable factor for monitoring cartilage damage. COMP has been studied as a biological marker for diagnostic and prognostic purposes. Musculoskeletal ultrasound (MSUS) imaging technology have allowed imaging of inflamed joints in rheumatoid arthritis patients. Objective: To assess the relationship between serum COMP levels and the articular cartilage damage based on sonographic knee cartilage thickness (KCT), disease activity, and other inflammatory markers in RA patients. Patients and Methods: Ninty participants were divided into two groups. Group I: Forty-five rheumatoid arthritis patients, which were subdivided according to disease activity into mild, moderate and sever, carried out from rheumatology outpatient clinic and inpatient in the Internal Medicine Department, Al-Zahraa University Hospital, all patients were female with their age ranging from 18 to 70 years with mean ± SD was (44.4±12.03). Group II: Forty-five age and sex-matched as control were included. Serum COMP level, Anti-Cyclic Citrullinated Peptides (ACCP), Rheumatoid Factor (RF), High Sensitive C- Reactive Protein (hs-CRP), were assayed. Also, sonographic knee cartilage thickness and Disease activity score (DAS28) were measured. Results: There were a highly significant increase the COMP level in the patient groups (the median is 301, and the interquartile range is 48-7954.9) in comparison to the control group (the median is 91.3, and the interquartile range is 39-146) with a P-value of 0.000, and highly significant increase the COMP level in the patient groups according to disease activity. There was a highly significant reduction of the knee cartilage thickness regarding lateral condyle (LC), medial condyle (MC) and intercondylar notch (IN) bilaterally compared with the control group. There were highly significant negative correlations between COMP and RKCTLC, RKCTIC and LKCTIC (P= 0.000), significant negative correlations between COMP and RKCTMC (P= 0.004), LKCTMC (P= 0.01), while there was no significant correlation between COMP and LKCTLC (P= 0.07), the mean of the right side was (P= 0.09) and the mean of the left side was (P= 0.22). Also, significant positive correlations between COMP and DAS28 (P= 0.03) was found. Conclusion: COMP can be used as a diagnostic biomarker for RA, based on its significant correlations with disease activity, ACCP, and knee cartilage thickness.