Interferon alpha gene expression and serum level association with low vitamin D levels in Egyptian female patients with systemic lupus erythematosus.

Background Patients with systemic lupus erythematosus (SLE) are prone to develop vitamin D (25(OH) D3) deficiency, due to several factors and there is an association between lower vitamin D levels and higher SLE disease activity. The aim of this research was to assess the prevalence of vitamin D deficiency in Egyptian female patients with SLE. Furthermore, we analyzed the potential relationship between this deficiency and SLE manifestations, disease activity, and its effect on interferon alpha (IFN-α) gene expression and serum level. Methods We evaluated the serum levels of vitamin D 25(OH)D3 and IFN-α by enzyme-linked immunosorbent assay (ELISA). IFN-α gene expression was measured by real-time polymerase chain reaction (PCR) assay in 123 Egyptian female patients with SLE and in 100 females as a healthy control group. Results Vitamin D deficiency was prevalent in 20.30%, while insufficiency was prevalent in 42.40% of the total group of patients. Serum levels of 25(OH)D3 were significantly decreased in the group of severe disease, and in the group of patients with lupus nephritis. 25(OH)D3 showed highly significant negative correlation with the SLE Disease Activity Index (SLEDAI) in the high activity group and lupus nephritis group. There was a significant negative correlation between 25(OH)D3 and IFN-α serum level and gene expression in all patients; more significant in the group with lupus nephritis. Conclusions The deficiency of 25(OH)D3 has a direct relationship with increase disease activity and nephritis in Egyptian SLE patients, suggesting the need for vitamin D supplementation in these patients. Also, it is directly correlated with increased secretion and gene expression of IFN-α, suggesting its role in pathogenesis of lupus nephritis, to be confirmed by further longitudinal observational studies.

The single-nucleotide polymorphism (SNP) of tumor necrosis factor α -308G/A gene is associated with early-onset primary knee osteoarthritis in an Egyptian female population.

The objective of the present study is to investigate if there is a potential association between the single-nucleotide polymorphisms (SNPs) of the tumor necrosis factor alpha gene (TNF-α -308G/A, rs1800629) and the susceptibility to and severity of early-onset knee osteoarthritis in the Egyptian female population. Genotype distributions and allelic frequencies of TNF-α -308G/A polymorphism were investigated in 210 knee osteoarthritis (OA) patients and 210 age-, sex-, and ethnicity-matched healthy controls (HC). Polymerase chain reaction-restricted fragment length polymorphism (PCR-RFLP) amplifications were implemented to determine TNF-α -308G/A SNP. Serum and synovial fluid levels of TNF-α, besides ESR and CRP, as laboratory markers for inflammation, were estimated for all patients and HC. Plain X-ray as well as MRI knee was done for grading of OA. Disease severity was estimated by Western Ontario and McMaster University Osteoarthritis scores. Percentages of TNF-α-G308A genotypes GG, AG, and AA were 85.7, 11.9, and 2.4% in OA patients and 54.7, 39.1, and 6.2% in controls, respectively. The frequencies of the GG genotype and G allele were significantly higher in subjects with knee OA than in HC (P = 0.04 and P < 0.001, respectively). Logistic regression analysis showed that the GG genotype and G allele are independently associated with increased risk for knee OA (odds ratio = 3.13, 95% confidence interval = 1.04-9.39, P = 0.04 for GG genotype, and odds ratio = 3.81, 95% confidence interval = 2.52-5.76, P = 0.001 for G allele). There is a close relationship between TNF-α-G308A polymorphism and individual susceptibility to and severity of early-onset knee OA in the Egyptian females.

Association of XRCC1 and OGG1 DNA repair gene polymorphisms with rheumatoid arthritis in Egyptian patients.

Rheumatoid arthritis (RA) is a chronic autoimmune disease and can lead to deformities and severe disabilities, due to irreversible damage of tendons, joints, and bones. Previous studies indicated that the DNA repair system was involved in the pathology of RA. In this study, we investigated the association of two XRCC1 (X-ray repair cross-complementing group 1) (rs25487 and rs25489) gene polymorphisms and two OGG1 (8-oxoguanine glycosylase 1) gene polymorphisms (rs159153 and rs3219008) with the susceptibility to RA in 320 Egyptians individuals (160 RA patients and 160 controls). Genotyping was performed using restriction fragment length polymorphism polymerase chain reaction. We found an association between variant XRCC1 (rs25487 and rs25489) genotype polymorphisms, OGG1 (rs3219008) genotype polymorphism, and RA disease susceptibility. Moreover, the presence of the Gln/Gln, Arg/His, and His/His genotypes of XRCC1 was significantly more likely to have bone erosion and extra-articular features in RA patients. Further, patient's carrying the OGG1 A/G and G/G genotypes more likely to have bone erosion. However, the AA genotype and A allele were significantly more likely to have extra-articular features. Also, there were no significant associations between C/T OGG1 gene polymorphism and RA susceptibility, bone erosion, and extra-articular features occurrence in RA patients. We concluded that the XRCC1-Arg/Gln, XRCC1-Arg/His, and OGG1 A/G polymorphism have a role in the development of rheumatoid arthritis disease. Also, these variant are associated with the severity of RA.

Influence of Matrix metalloproteinase 1 and 3 genetic variations on susceptibility and severity of juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease affecting children aged less than 16 years, characterized by chronic synovitis, cartilage damage, and bony erosions mediated by matrix metalloproteinases (MMPs), mainly MMP-1 and MMP-3. The purpose of this study was to investigate MMP-1 and MMP-3 gene polymorphisms in patients with JIA, the role of genes in susceptibility to JIA, and their associations with JIA activity and prognosis. Case-control study included 100 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 100 healthy children, age and sex matched, as controls. The MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of MMP-1 and MMP 3 were measured by enzyme-linked immunosorbent assay. There were significant differences between patients with JIA and control groups regarding the genotype and allele frequencies distributions of both MMP-1 1G/2G and MMP-3 5A/6A polymorphisms. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in patients with JIA than in controls (OD = 2.8, P = 0.002). The prevalence of MMP-1 2G and 6A allele for MMP-3 polymorphism was found to be significantly associated with persistent oligoarticular, rheumatoid factor (RF)-positive polyarthritis, and systemic JIA groups. There were significantly increased serum levels of MMP-1 and MMP-3 associated with 2G/6A haplotype in the patient group, especially with the polyarticular RF (+ve) group than in other groups and the control group. MMP-1 and MMP-3 haplotypes could be useful genetic markers for JIA susceptibility and severity in the juvenile Egyptian population. Moreover, our data further support the use of serum MMP-3 and MMP-1 as specific markers of disease activity in JIA.

The role of serum IL-17 and IL-6 as biomarkers of disease activity and predictors of remission in patients with lupus nephritis.

AIM: To determine the role of IL-17 and IL-6 in the pathogenesis of SLE as biomarkers of disease activity and predictors of remission and outcome of therapy in patients with active lupus nephritis. METHODS: The study was carried out on 72 SLE female patients and 70 sex- and age-matched normal healthy subjects as controls. SLE disease activity was assessed in all patients with (SLEDAI-2k scores). Plasma levels of IL-6, and IL-17 were measured by enzyme linked immunosorbent assay and their levels were correlated with clinical manifestations of the disease and (SLEDAI-2k). ROC curve analysis was performed to determine the validity of both cytokines in prediction of activity and remission of active lupus nephritis. RESULTS: SLE patients were found to have significantly higher levels of IL-17 (p<0.001) and IL-6 (p<0.001), in relation to normal subjects. Active group of patients had higher levels of both cytokines than the inactive one (P<0.001). Elevated serum levels of both cytokines were associated with active lupus nephritis, anemia and positively correlated with SLEDAI-2k scores (P=0.025 for IL-17 and P<0.001 for IL-6). There was a significant positive correlation between IL-6 and IL-17 serum concentrations during periods of disease activity (r=0.497, P=0.005) as well as during remission (r=0.662, P<0.001). ROC curve analysis for IL-6 and IL-17, as predictor of disease activity reviled, optimal cutoff level of 12.3 pg/ml and 19.7 pg/ml, with AUC=0.93, and 0.95, for both cytokines respectively, while as predictors of remission of active lupus nephritis, provide a cutoff value of IL-6 at 20.8 pg/ml, with AUC 0.80, and a cutoff value of IL-17 at 27.0 pg/ml, with AUC 0.82. CONCLUSION: In conjunction with their major role in pathogenesis of SLE, baseline serum levels of IL-6 and IL-17 can be used as sensitive biomarkers for disease activity, as well as predictors of remission of lupus nephritis.

The role of CTLA-4 exon-1 49 A/G polymorphism and soluble CTLA-4 protein level in egyptian patients with Behçet's disease.

This study analyzed the association of the A/G SNP at position +49 of exon-1 in the CTLA-4 gene to the susceptibility and clinical manifestations of Behcet's disease (BD). It was performed on 60 Egyptian BD patients and 95 age- and sex-matched healthy controls. The genotypes for the +49 A/G polymorphism of the CTLA-4 gene were determined by PCR-RFLP, while the serum level of CTLA-4 protein was measured by ELISA. CTLA-4 +49 A allele (P < 0.001, OR = 3.084, and CI (95%) = 1.90-4.99) and A/A genotype (P < 0.001, OR = 6.643, and CI (95%) = 2.58-17.10) frequency distribution was significantly more increased in patients than in the controls, with no significant differences between males and females with regard to the genotype or allele frequency distribution. A/A genotype was associated with a more reduced expression of sCTLA-4 protein in patients than in the controls (1.76 ± 0.19 versus 1.91 ± 0.30, resp; P < 0.0007). In addition, it is associated with the occurrence of ocular and vasculitic manifestations of BD in the patient group. The CTLA-4 gene could be considered as a susceptibility and a disease-modifying gene to BD in Egyptian population that needs further confirmatory studies on larger cohorts.

Influence of interleukin-4 gene polymorphisms and interleukin-4 serum level on susceptibility and severity of rheumatoid arthritis in Egyptian population.

BACKGROUND: Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease in which interleukin-4 (IL-4) plays an important role. This study aimed to investigate the influence of IL-4 variable number of tandem repeats (VNTRs) and IL-4-590 promoter polymorphisms on RA susceptibility, activity and severity in Egyptian population. MATERIALS AND METHODS: One hundred and seventy-two RA patients and 172 controls were enrolled in this study. IL-4 VNTR and IL-4-590 promoter polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum IL-4 and anti-cyclic citrullinated peptides (anti-CCPs) antibody concentrations were measured by enzyme linked immunosorbent assay (ELISA). RESULTS: Subjects with IL-4-590 TT genotype were significantly more likely to develop RA. IL-4 VNTR 1/1 genotype, IL-4-590 TT and CT genotypes were significantly more associated with erosive RA and positive anti-CCP antibody. RA severity parameters were significantly increased, while, IL-4 level was significantly decreased in RA patients with IL-4 VNTR 1/1 and IL-4-590 TT genotypes. Only patients with IL-4-590 TT genotype showed a significant increase of all RA activity parameters. CONCLUSION: IL-4 VNTR and IL-4-590 promoter polymorphisms may be helpful for assessing RA severity in Egyptian population. Moreover, IL-4-590 promoter polymorphism may be associated with increased risk and activity of RA.