Long noncoding RNAs (CTC-471J1.2, NeST) as epigenetic risk factors of active juvenile lupus nephritis: a case-control study.

BACKGROUND: Measurement of the circulating levels of long-non-coding RNAs (lncRNAs) in lupus nephritis (LN) patients could dramatically explore more insights about the disease pathogenesis. Hence, we aimed to quantify the level of expression of CTC-471J1.2 and NeST in LN patients and to correlate it with the disease activity. METHOD: This case-control study was conducted on a group of children with juvenile LN attending to Mansoura University Children's Hospital (MUCH). Demographics, clinical, and laboratory findings were collected besides the measurement of lncRNAs by quantitative real-time PCR. RESULTS: The expression level of lncRNAs-CTC-471J1.2 was significantly down-regulated in children with active LN versus inactive cases or controls. In contrast, the NeST was significantly up-regulated in active LN cases. A significant correlation was found between CTC-471J1.2 expression and LN activity parameters. Additionally, both lncRNAs showed a reasonable sensitivity and specificity in differentiation of active LN. A regression analysis model revealed that CTC-471J1.2 and NeST were independent predictors of active nephritis. CONCLUSION: The expression level of circulatory lncRNAs-CTC-471J1.2 and NeST can be used as sensitive and specific biomarkers for active LN. Furthermore, both could serve as predictors for nephritis activity.

Association of the Gelatinase B/Metalloproteinase 9 (MMP-9) Gene Haplotype in Systemic Lupus Erythematosus (SLE) in the Pediatric Egyptian Population.

Permanent systemic inflammation is a defining feature of systemic lupus erythematosus (SLE), which affects multiple organs. Gelatinase B/matrix metalloproteinase-9 (MMP-9) is an essential protease investigated in inflammation that has been linked to SLE. The study's objective was to investigate the relationship between the rs3918249 T/C and rs17576 A/G SNPs in the MMP-9 gene with SLE. The study was conducted with 100 SLE cases and 100 age/sex-matched healthy individuals. TaqManTM SNP was used for genotyping by real time PCR on the Artus Rotor-Gene Qiagen equipment. Haplotypes (TG: OR = 0.226, 95% CI = 0.119−0.429) and (CA: OR = 0.36, 95% CI = 0.2206−0.631), both with a p-value < 0.001 were substantially linked to a lower incidence of SLE. Conversely, the risk of SLE was not associated with the individual SNPs studied. The haplotype analysis was more significant than the SNP analysis and may correlate with the decreased risk of SLE in children and adolescents in Egypt.

Association of CD14 genetic variants and circulating level with systemic lupus erythematosus risk in Egyptian children and adolescents.

Aim: To demonstrate whether sCD14 and CD14 (rs2569190 A/G and rs2569191 C/T) genetic variants are associated with systemic lupus erythematosus (SLE) risk, for the first time, in Egyptian pediatrics and adolescents. Materials & methods: sCD14 concentrations were determined in plasma of 95 SLE cases and 98 healthy controls using ELISA assay. Genotyping was performed using TaqMan technology. Results: sCD14 levels were elevated in SLE. Individuals with T, CT and TT genotypes in rs2569191 were of significant risk (odds ratio = 1.471-2.035, 95% CI = 1.138-3.471) and those with combined CT+TT and haplotype GT were of higher risk of SLE (odds ratio = 1.660-1.758, 95% CI = 1.003-3.106, p < 0.05). sCD14 levels and CD14 polymorphism were not correlated with SLE clinical and laboratory features. Conclusion: In SLE, sCD14 levels are associated with rs2569190 A/G. Genotype CT+TT in rs2569191 C/T and haplotype GT are associated with SLE risk in Egyptian pediatric and adolescents.

Plasma interleukin-22 level, variants in interleukin-22 gene polymorphism, and the severity of systemic lupus erythematosus among Egyptian pediatric and adolescents.

OBJECTIVES: Our purpose was to investigate, for the first time, genotypes and alleles distribution of two single nucleotide polymorphisms (SNPs) of interleukin 22 (IL-22) (rs1012356 and rs2227485) in Egyptian pediatric and adolescents with systemic lupus erythematosus (SLE) and to evaluate the plasma IL-22 levels and their association with gene polymorphism and SLE risk and severity. METHODS: The TaqMan™ SNP genotyping assay on a real-time polymerase chain reaction (PCR) system was employed to evaluate the polymorphism's genotypes. Plasma IL-22 levels were determined by using an enzyme-linked immunoabsorbent assay (ELISA). RESULTS: The frequencies and genotypes of rs2227485 and rs1012356 in IL-22 between SLE patients and controls also haplotypes formed by the same SNPs revealed no statistically significant difference (p > 0.05). Otherwise, logistic regression analysis revealed that patients carrying rs1012356 "TA + AA" genotype had increased risk for prediction of SLE activity (OR = 1.610, 95% CI = 1.339-2.760, p = 0.034) by lowering plasma IL-22 level. CONCLUSIONS: Among Egyptian pediatric and adolescents, we confirm a combined model "TA + AA" in rs1012356 (A/T) of IL-22 in regression analysis, as an independent predictor for SLE activity by lowering IL-22 plasma levels. Despite neither SNP rs2227485 A/G in IL-22 gene nor haplotypes formed by the same two SNPs (rs2227485 A/G and rs1012356 A/T) were significantly associated with the clinical and/or laboratory manifestations of SLE.

Single-nucleotide polymorphisms (SNPs) of antioxidant enzymes SOD2 and GSTP1 genes and SLE risk and severity in an Egyptian pediatric population.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease associated with increased oxidative stress that participates in immune dysregulation, and injury resulting in loss of immune tolerance and increased auto-antibody production. This study was designed to investigate the effects of genetic polymorphisms of the antioxidant enzymes genes that code for SOD2 (rs2758332) and GSTP1 (rs1695) on SLE risk and severity in Egyptian children and adolescents cohort from Delta region. METHODS: The frequencies of these genes polymorphic variants were compared between 100 SLE children and adolescents and 100 healthy control subjects. Single-nucleotide polymorphisms (SNPs) of the two antioxidants were determined using TaqMan SNP genotyping assay. RESULTS: Individuals with the TT and CT genotypes of rs2758332 in the SOD2 gene were of significant risk for SLE patients (OR = 1.831, 95% CI = 1.082-3.101, P = 0.024) and (OR = 1.864, 95% CI = 1.136-3.059, P = 0.014), respectively. Cases who have combined CT + TT genotype were of significant higher risk of SLE (OR = 1.851, 95% CI = 1.156 - 2.962, P = 0.010). While, they did not show any significant association between SOD2 genotypes or alleles with SLE clinical features. In case of the SNP rs1695 in the GSTP1 gene, no significant associations of genotypes or alleles with SLE risk or with SLE clinical features were detected. CONCLUSIONS: This study among Egyptian children and adolescents showed a strong association of the SOD2 rs2758332 not GSTP1 rs1695 polymorphism with the risk of SLE disease.

Pro-inflammatory adipocytokines, oxidative stress, insulin, Zn and Cu: Interrelations with obesity in Egyptian non-diabetic obese children and adolescents.

PURPOSE: To investigate the inter-relationships between adipocytokines, oxidative stress, insulin, Zn and Cu and obesity among Egyptian obese non-diabetic children and adolescents. PATIENTS AND METHODS: 72 obese children and adolescents of both sexes (5-17 years) were recruited for the study. 40 healthy normal non-obese persons of matched ages and sexes were used as control group. Lipid profile, tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and leptin levels were measured. Malondialdehyde (MDA) and reduced glutathione (GSH) concentrations and superoxide dismutase (SOD) activity were estimated. Micronutrients (Zn and Cu) concentrations in addition to insulin and fasting blood sugar (FBS) levels were also evaluated. Estimation of insulin resistance (homeostatic model assessment (HOMA-IR)) was derived from FBS measurements. RESULTS: Significant elevations (P<0.001) in TNF-α, IL-6, leptin, MDA, Cu and FBS levels and significant decreases (P<0.001) in GSH, Zn levels and SOD activity were detected among obese individuals as compared with control group. Insulin and triglyceride levels were significantly increased in obese male children and HDL-cholesterol level was increased significantly in obese adolescent females compared to controls. However, total cholesterol and LDL-cholesterol levels were significantly high in all obese cases as compared with controls. Insulin resistance was detected in 100% of the patients. CONCLUSIONS: We concluded that obesity with pro-inflammatory adipocytokines and hypozincemia together by many mechanisms participate in excessive oxidative stress and are highly associated with inflammation and the development of obesity-related complications. Obesity represents a critical risk factor for development of insulin resistance status.