Association of Genetic Variants of the Interleukin-17F rs763780 and its Circulating Level in Psoriasis Patients in Egypt.

Psoriasis is a chronic autoimmune disease affecting the skin and joints, IL- 17 family has been shown to be the major effector cytokine in its pathogenesis. This study aimed to investigate genetic polymorphism of IL-17F (rs763780) and evaluate the impact of this polymorphism on circulating levels of IL-17F as a potential risk locus for psoriasis. 60 patients suffering from chronic plaque psoriasis and 60 healthy controls were genotyped for the IL-17F (rs763780) using an Amplification Refractory Mutation System -PCR (ARMS-PCR) method. Measurement of serum IL-17F was also done by ELISA. There was a significant difference in frequency between TT and TC genotypes (OR= 2.74, 95%CI=1.04 -7.4, P=0.04) and TT and CC genotypes (OR=10.9, 95%CI=1.3-91.3, P=0.007). Moreover, the TC and CC genotypes were associated with increased risk of psoriasis in comparison with the TT genotype. (OR= 3.8, 95% CI: 1.5- 9.4, P= 0.003). The mutant allele, C, was significantly associated with an increased risk of psoriasis compared to that with the wild T allele, T (OR= 4.1, 95% CI: 1.9- 9.1, P= 0.0002). Serum level of IL-17F was higher among psoriasis patients ( 25.7±3.8pg/ml) than healthy controls ((15.1±2.1 pg/ mL). In conclusion, IL17F polymorphism (rs763780) is associated with increased risk of psoriasis and may influence the level of production of IL-17F with subsequent effects on the pathogenesis of psoriasis.

Anti-PLA2R and anti-THSD7A as Diagnostic Serological Markers of Idiopathic Membranous Nephropathy: A Single Centre Study.

Idiopathic Membranous Nephropathy (IMN) is a renal-limited autoimmune disease and accounts for approximately 80% of MNs. This study aimed to evaluate the role of circulating Anti-PLA2R and anti-THSD7A autoantibodies in the diagnosis and differentiation between primary and secondary MN. This study was conducted on 58 adult patients with biopsy-proven membranous glomerulopathy (MGN). All were subjected to measurement of Anti-PLA2R1 by an Enzyme-Linked Immunosorbent Assay and anti-THSD7A was detected by an indirect immunofluorescence assay. Among the 58 patients, 79.3% were diagnosed as IMN, and 20.7% as secondary membranous glomerulopathy (SMN). Among IMN patients, 32 patients (69.6%) showed positive anti-PLA2R1 antibodies, 2 patients (4.3%) were positive for anti-THSD7A antibodies and the remaining 12 patients (26.1%) were negative for both types of antibodies. Patients with SMN were negative for the two antibodies. The IMN patients had lower serum creatinine compared to the SMN patients (P=0.017). In conclusion, the study demonstrates that approximately 70% of patients with idiopathic membranous nephropathy have antibodies against PLA2R indicating that Anti-PLA2R may be fast, easy, relatively sensitive, and non-invasive test for diagnosis of IMN..

Combination of Procalcitonin, CRP and CD11b Biomarkers in Early Detection of Neonatal Sepsis.

The study aimed at comparing the diagnostic performances of CRP, PCT and CD11b in neonatal sepsis and evaluating the effectiveness of the sepsis score system when using a combination of various biomarkers. The study was conducted on 90 neonates divided into 3 equal groups; a group with proven sepsis, suspected sepsis and healthy newborns. All were subjected to measurement of CPR by Latex agglutination, serum Procalcitonin by ELISA and CD11b by flow cytometry. On comparing the three biomarkers; PCT (Serum procalcitonin) was associated with the highest (AUC) area under the curve followed by CD11b and CRP recording the smallest value. However, the AUC of the combined sepsis score was much higher than individual biomarkers. Although the sensitivity of individual biomarkers from procalcitonin to CD11b and lastly CRP but the sensitivity and specificity of the sepsis score showed higher values compared to those of individual biomarkers. In conclusion, the study demonstrate that combination of CRP, CD11b and, procalcitonin can enhance diagnostic discriminative power over traditional tests and overcome the drawbacks of each test alone with greater diagnostic accuracy.

Toll Like Receptor-4 Gene Polymorphism and Susceptibility to Pulmonary Tuberculosis.

Tuberculosis (TB) affects human life globally for a long time. The difference in clinical outcome of infection suggests that host genetic makeup is responsible for such variability. Toll like receptors (TLRs) are pattern recognition receptors and have a significant role in mycobacterial recognition by the innate immune system. TLR-4 is the key receptor in initiation of innate immunity against M. tuberculosis. This study investigated whether variants in TLR-4 896A/G (Asp299Gly) and TLR-4 1196C/T (Thr399Ile) genes are related with susceptibility or resistance to pulmonary tuberculosis (PTB) in Saudi population. Genotyping of TLR-4 896A/G, TLR-4 1196C/T gene was performed by polymerase chain reaction followed by restriction fragment length polymorphism (PCR -RFLP) in 60 PTB patients and 60 control subjects. The A allele at (896A/G) was more frequent in the control group while G allele was more common in PTB patients. The frequency of T allele of (1196C/T) polymorphism was significantly increased in PTB patients as compared to the control group (P < 0.001; Odds ratio (OR) 2.79, 95% Confidence interval (CI) 1.65-4.72). A trend toward increased frequency of TT and CT genotypes of TLR4 at (1196C/T) were also observed in PTB patients as compared to control group (48.3% vs. 26, 7%, and 21.7% vs. 15%), respectively. This study suggests that that TLR4 polymorphism especially TLR4 rs4986791 may be associated with increase susceptibility to pulmonary tuberculosis, and C allele of rs4986791 is a promising protective factor for tuberculosis susceptibility in Saudi population.

Association of CTLA-4 +49 A/G and CT60 Gene Polymorphism with Graves' Disease.

Graves' disease (GD) is an organ specific autoimmune disease of thyroid gland with genetic and environmental causes. One of genetic factors that have been implicated in the development of this disease is CTLA-4 gene polymorphism. This study aimed to investigate the association of CTLA-4 polymorphisms at position +49A/G, and CT60 with susceptibility to Graves' disease in Saudi patients. 40 adult Saudi patients with GD and 30 healthy controls were genotyped for the +49 A/G and CT60 of the CTLA4 gene using restriction fragment length polymorphism analysis (RFLP). There was a significant difference between GG genotype and AA genotype in GD patient in comparison to control group (P = 0.007), GG genotype was the most prevalent and the AA genotype was less frequent in the GD patients. The G allele at position +49 was more frequent in patients with GD than in the control group. Statistically significant differences between A and G alleles of GD patient and control groups were found (p= 0.003; OR =2.85 and 95% CI =1.4-5.7). The G allele in CT60 was higher in GD patients than those in controls (OR=2.8, 95% CI =1.4-5.7 and P = 0.004). In conclusion, CTLA-4 polymorphism at position 49 and CT60 may be potentially associated with the risk of GD among Saudi patients.

Expression of CD64 on Surface of Circulating Monocytes in Systemic Lupus Erythematosus Patients: Relation to Disease Activity and Lupus Nephritis.

CD64 is a type of integral membrane glycoprotein known as FC receptor that binds monomeric IgG-type antibodies with high affinity. It is more commonly known as FC gamma receptor 1 (FC?R1) and it is expressed on monocytes surface. The goal of this study was to investigate the association of CD64 expression on the surface of peripheral blood monocytes of systemic lupus erythematosus patients with disease activity, and lupus nephritis. 30 SLE patients were enrolled into this study. They were subdivided into: 15 SLE patients with lupus nephritis and 15 SLE patients without lupus nephritis. In addition,Together with 25 age and sex matched healthy volunteers were enrolled as controls group. Disease activity was defined by SLE Disease Activity Index (SLEDAI) score and the renal Systemic Lupus Erythematosus Disease Activity Index (rSLEDAI) score. Surface expression of CD64 on peripheral blood monocytes was evaluated by Flowcytometry. Renal biopsies of Lupus nephritis patients was obtained and evaluated using the International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification scheme. There was a statistically significant difference in surface expression of CD64 on circulating monocytes (P > 0.001) in SLE patients with nephritis especially those with class II/III as compared to SLE without nephritis and healthy controls. The mean fluorescent intensity of CD64 staining correlated positively with markers of systemic inflammation, lupus nephritis, SLEDAI and rSLEDAI scores. In conclusions, surface expression of CD64 on circulating monocytes reflects systemic inflammation, renal injury and could be used as a rapid approach and good biomarker for disease activity and lupus nephritis in SLE patients.

Serum Level of Interleukin-37 and Expression of Its mRNA in Ankylosing Spondylitis Patients: Possible Role in Osteoporosis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease of the axial skeleton.Interleukin-37 (IL-37) is a member of IL-1 family cytokines, that downregulate expression of pro-inflammatory cytokines in chronic inflammatory diseases. The aim of the work is to investigate role of IL-37 in AS disease activity and osteoporosis. Twenty-five patients with AS and 25 controls were enrolled into this study. They were subjected to full clinical examination including assessment of disease activity according to the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Serum IL-37 levels and IL-37 mRNA relative concentration were measured by enzyme-linked immunosorbent assay (ELISA) and quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) respectively. Bone mineral density (BMD) was determined using dual energy X-ray absorptiometry (DEXA). Spine radiographs were scored using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Mean serum IL-37 level was significantly higher in AS patients compared with the controls (P < 0.001) and significantly elevated in AS patients with osteoporosis (P < 0.05). IL-37 mRNA gene expression showed a significant increase expression in active AS patient (25 folds) as well as in inactive patient (12 folds) as compared to controls . In conclusion, serum IL-37 and its mRNA expression is increased in AS patients with special consideration in patient with Osteoporosis and correlates with disease activity and BMD which indicate that IL-37 may provide a novel research target for pathogenesis and therapy of AS. .

Transfusion-transmitted virus infection in hemodialysis patients in Arar, Saudi Arabia: Prevalence, predictors and genotyping.

Transfusion-transmitted virus (TTV) is a single-stranded DNA virus that was identified in patients with post-transfusion hepatitis of non-A-to-G type. Patients with chronic renal failure on maintenance hemodialysis (HD) have a higher risk of viral infections, and the prevalence of TTV infection is common. The aim of our study was to detect TTV-DNA and its genotype in HD patients. A case-control study compromising of 63 patients on maintenance HD therapy at the Nephrology Center of Central Arar Hospital and 100 healthy individuals who were tested for TTVDNA and its genotype by semi nested-polymerase chain reaction with primers derived from the conserved open reading frame 1 (ORF1) region followed by digestion with NdeI and PstI restriction enzyme. The results show that the prevalence of TTV in HD patients was high and statistically significant; 42.9% compared with 19% in the control group. History of blood transfusion was the only significant predictor, and we found that age of patients, duration of HD, hepatitis B and C infection, aspartate aminotransferase and alanine aminotransferase levels were not significant predictors of TT virus positivity in HD patients. TTV genotype 1 (G1) was found to be the most common genotype among both HD and healthy controls. The prevalence of TTV among HD patients was significantly higher than that in healthy individuals. History of blood transfusion was the only significant predictor of TTV positivity among them. Genotype 1 was the most predominant type among HD and healthy individuals. Further studies on TTV in peritoneal dialysis patients and transplant patients are needed.

Serum Interleukin-33 in Behcet's Disease: Its Relation to Disease Activity and Clinical Manifestations.

Behcet's disease (BD) is a chronic systemic inflammatory disorder characterized by a course of remissions and exacerbations of unpredictable frequency and duration . Pro- inflammatory cytokines seem to be responsible for the enhanced inflammatory response in BD. AIM OF THE WORK: This study aimed to investigate serum levels of IL-33 in patients with Behcet's disease (BD) and their relationship to disease activity and clinical manifestations. Thirty patients with BD were enrolled and subjected to assessment of disease activity according to Behcet's Disease Current Activity Form (BDCAF) score. Serum IL-33 levels were determined using Enzyme-Linked-Immunosorbent Assay (ELISA). Thirty age and sex matched rheumatoid arthritis patients and thirty healthy volunteers were included in this study as control groups. Serum IL-33 level was 132.5±19 pg\ml, 101.2±20.1 pg\ml and 31.5±10.5 pg\ml in RA, BD and healthy control groups respectively. IL-33 was significantly higher in BD patients (101.2±20.1pg/ml) as compared to healthy controls (31.5±10.5 pg/ml) but lower than rheumatoid arthritis patients (132.5±19.1 pg/ml). Levels of IL-33 were significantly increased in BD patients with skin lesions (Erythema nodosum & Acneiform lesions) and ocular lesions (retinal vasculitis) (P<0.05), and a positive correlation was found between BDCAF score and IL-33serum levels (r=0.9, P<0.001). In conclusions, serum IL-33 level is elevated in active BD patients with skin and ocular affection and correlates with disease activity.

Serum Level of Growth Arrest-Specific 6 (Gas6) Protein and Genetic Variations in the Gas6 Gene in Patients with Type 2 Diabetes Mellitus.

Growth arrest-specific protein 6 (Gas6) belongs to a family of vitamin K-dependent coagulation proteins. Plasma levels of Gas6 are associated to altered glucose tolerance. This study aimed at determining whether c.843+7G>A Gas6 polymorphism is associated with the development of type 2 diabetes mellitus. The study included 50 patients with type 2 diabetes and 40 matched controls. The Gas6 protein was measured in serum using ELISA and Gas6 gene polymorphism by polymerase chain reaction-Restriction Fragment Length Polymorphism. The GG genotype was the most prevalent in the diabetic patient. The frequency of A allele in the diabetic group was lower than the control group (P < 0.05). Serum concentrations of Gas6 were lower among type 2 diabetes patients than controls (P < 0.001). Since the AA genotype was expressed at a lower frequency in type2 diabetes patients compared to controls, a protective role for this Gas6 variant in type 2 diabetic patients may be concluded.

Interleukin-18 gene polymorphisms in systemic lupus erythematosus: relation to disease status.

Systemic lupus erythematosus (SLE) is a multisystem autoimmune connective tissue disorder characterized by loss of self-tolerance causing immune-mediated tissue destruction and various clinical presentations Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in chronic inflammation and autoimmune disorders. This study investigates polymorphisms of the IL-18 gene in SLE patients at positions -607 and -137 of the promoter to elucidate their possible roles in the activity and severity of this disease. Fifty SLE patients and fifty unrelated healthy control group were included. AII SLE patients underwent thorough clinical examination and SLE disease activity assessment using SLEDAI. Genomic DNA was extracted from peripheral venous blood. Sequence-specific primer PCR analysis were used to genotype the DNA samples for SNP-607and SNP-137, while plasma IL-18 concentrations of patients and control subjects were measured by enzyme-linked immunosorbent assay. The frequency of SNP-607/CC genotype showed significant increase (P < 0.05), while genotype SNP-607/CA showed significant decrease (P < 0.05) in SLE patients as compared to the control group. Significantly elevated levels of plasma IL-18 were found in patients compared to controls (P < 0.001) and those with genotype CC at -607 demonstrated the highest IL-18 level (331.74 +/- 36.48 pg/mL). Serum IL-18 levels showed significant positive correlations with the ESR 1st hr. (r = 0.89), protein/creatinine ratios (r = 0.88), anti-dsDNA titers (r = 0.44) and SLEDAI scores (r = 0.91). In contrast, significant negative correlations were found with HB% r = -0.68, creatinine clearance (r = -0.87) and C3 (r = -0.81). In addition, a statistically significant association was found between IL-18 of CC -607 genotype and lupus nephritis, arthritis and immunological disorders. In conclusion, IL-18 promoter gene polymorphisms at position -607 may contribute to SLE activity and accelerate SLE development by enhancing production of IL-18 protein in SLE patients.