Genome-wide association study for systemic lupus erythematosus in an egyptian population.

Systemic lupus erythematosus (SLE) susceptibility has a strong genetic component. Genome-wide association studies (GWAS) across trans-ancestral populations show both common and distinct genetic variants of susceptibility across European and Asian ancestries, while many other ethnic populations remain underexplored. We conducted the first SLE GWAS on Egyptians-an admixed North African/Middle Eastern population-using 537 patients and 883 controls. To identify novel susceptibility loci and replicate previously known loci, we performed imputation-based association analysis with 6,382,276 SNPs while accounting for individual admixture. We validated the association analysis using adaptive permutation tests (n = 109). We identified a novel genome-wide significant locus near IRS1/miR-5702 (Pcorrected = 1.98 × 10-8) and eight novel suggestive loci (Pcorrected < 1.0 × 10-5). We also replicated (Pperm < 0.01) 97 previously known loci with at least one associated nearby SNP, with ITGAM, DEF6-PPARD and IRF5 the top three replicated loci. SNPs correlated (r 2 > 0.8) with lead SNPs from four suggestive loci (ARMC9, DIAPH3, IFLDT1, and ENTPD3) were associated with differential gene expression (3.5 × 10-95 < p < 1.0 × 10-2) across diverse tissues. These loci are involved in cellular proliferation and invasion-pathways prominent in lupus and nephritis. Our study highlights the utility of GWAS in an admixed Egyptian population for delineating new genetic associations and for understanding SLE pathogenesis.

Diagnostic value of the serum Midkine in patients with rheumatoid arthritis.

Early diagnosis and detection of rheumatoid arthritis (RA) activity which is a potential therapeutic target, depends mainly on clinical presentation. However, laboratory tests may contribute to diagnosis and disease activity assessment of RA. This study aims to evaluate the accuracy of serum Midkine as serological marker for RA diagnosis and its activity detection. All patients with RA were recruited during the period from January 2016 to August 2018 in addition to healthy subjects as control. Serum Midkine level was estimated using enzyme immunoassay. The accuracy was determined for serum Midkine against the used American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA diagnosis and disease activity score derivative for 28 joints-erythrocyte sedimentation rate (ESR) score for assessment of RA disease activity. A total of 211 of patients with RA (group I) were enrolled in this study with 112 healthy subjects (group II). Patients with RA were divided into two subgroups according to the disease activity; patients with active RA (group IA) and RA in remission (group IB). We detected that the area under curve (AUC) of serum Midkine level (AUC=0.851) was significantly lower than that of rheumatoid factor IgM and anti-cyclic citrullinated peptide IgG for RA diagnosis. However, Midkine presents a significantly higher diagnostic accuracy (AUC=0.939) in detecting RA activity than that offered by C reactive protein (CRP) or ESR. Our study suggested that serum Midkine is a potential serological marker for detection of active inflammatory state with higher diagnostic accuracy than other inflammatory markers as CRP or ESR. Therefore, it can be used as an inflammatory marker for detection of disease activity rather than diagnosis of RA.

Systemic lupus erythematosus, hypoparathyroidism, and hemolytic anemia in a patient with Wilson's disease.

The authors report a female case of systemic lupus erythematosus (SLE) that was diagnosed as Wilson's disease (WD) when neurological manifestations were evident three years after the first admission. The brain imaging studies showed bilateral symmetrical basal ganglia involvement, slit lamp examination revealed Kayser-Fleischer ring of the cornea, and 24-hour urinary copper and serum ceruloplasmin also confirmed the diagnosis. The patient also had hemolytic anemia and hypoparathyroidism, which are rare presenting features of WD. SLE may be associated with WD, and presence of neurological, behavioral, or liver function abnormalities should raise the suspicion, even without apparent features of WD.

Adipocytokines, inflammatory, epigenetic instability & angiogenesis biomarkers in type 2 diabetic Egyptian women with breast cancer.

Obesity is the main determinant of type 2 diabetes. Some adipocytokines play important roles in diabetic complications. Lipid transport is an important aspect of lipid metabolism in cancer. Present study aimed to evaluate the effect of some adipocytokines, inflammatory, epigenetic instability & angiogenesis biomarkers in type 2 diabetic Egyptian women with breast cancer. Study Design was performed on eighty females divided into 20 healthy subjects (Group I), 20 patients with type 2 diabetes (Group II), 20 patients with breast cancer (Group III) & 20 patients with diabetes and breast cancer (Group IV). Demographic data & body mass index have been collected. Biochemical analysis included fasting & postprandial blood glucose, lipid profile, fatty acid-binding proteins-4 (FABP-4), tumor necrosis factor-α (TNF-α), vascular endothelial growth factor (VEGF), 8-hydroxy-2'-deoxyguanosine (8-OHdG) & thioredoxin reductase (TrxR) activity. Results revealed significant increase in FABP-4, TNF-α, VEGF, 8-OHdG and significant decreased TrxR activity in diabetic patients with breast cancer in comparison with other groups. These changes were evident in breast cancer subjects than diabetic and healthy cases and in diabetic than healthy cases. Conclusion: This study confirmed the role of FABP-4 in pathogenesis of type 2 diabetes & breast cancer via enhancing angiogenesis, inflammatory and epigenetic instability biomarkers.

2-D speckle-tracking assessment of left and right ventricular function in rheumatoid arthritis patients with and without disease activity.

OBJECTIVES: Disease activity has been considered as independent cardiovascular risk factor in rheumatoid arthritis (RA) patients. We aimed to evaluate the effect of RA disease activity on left ventricular (LV) and right ventricular (RV) functions by speckle tracking echocardiography (STE). METHODS: 120 patients with RA without evidence of cardiovascular disease and 40 healthy control subjects were included. Disease activity was evaluated according to Simplified Disease Activity Index (SDAI) score and Disease Activity Score 28 (DAS28). LV and RV functions were assessed using conventional echocardiography and global longitudinal strain (GLS) technique measured by STE. RESULTS: 81 patients had active disease while 39 patients were in remission. The LV and RV GLS value for active RA patients was reduced compared to RA patients in remission and control group (p = <0.001). There was a significant correlation between RA disease activity scores level and LV GLS value, increasing levels of disease activity was associated with worse LV GLS (r = -0.802, p value = <0.001) and r = -0.824, p value = <0.001) for SDAI and DAS28 scores respectively. Also, there were significant correlations between RA disease activity scores level and RV GLS value as the disease activity level increases the RV GLS value become worse (r = -0.682, p value = <0.001) and r = -0.731, p value = <0.001) for SDAI and DAS28 scores respectively Receiver operating characteristic (ROC) curve analysis showed that SDAI score and DAS28 were predictive for reduced LV GLS with a cut off value of >7 and >2.8 respectively with sensitivity of 77.6%, specificity of 85.0% and area under ROC curve = 90.4 for SDAI score and with sensitivity of 89.7%, specificity of 71.7% and area under ROC curve = 89.4 for DAS28 score. Also, SDAI score and DAS28 were predictive for reduced RV GLS with a cut off value of >11 and >3 respectively with sensitivity of 73.1%, specificity of 93.5% and area under ROC curve = 91.6 for SDAI score and with sensitivity of 84.6%, specificity of 80.4% and area under ROC curve = 90.8 for DAS28 score. CONCLUSION: Disease activity in patients with rheumatoid arthritis is associated with lower left and right ventricular function. Disease activity scores can predict subclinical left and right ventricular dysfunction.

Assessment of leptin and resistin levels in non-obese multiple myeloma patients and their relation with Ig level and disease stage.

INTRODUCTION: Multiple myeloma (MM) accounts for approximately 0.8% of all cancer diagnoses and 0.9% of cancer deaths. Leptin receptors were expressed on CD34(+) cells. Resistin receptors were expressed on inflammatory cells and pro-inflammatory cytokines increase the expression of resistin on monocytes. AIM OF WORK: To assess the level of leptin and resistin in non-obese multiple myeloma patients and to study their relation with Ig level and disease stage. SUBJECTS & METHODS: 32 subjects were included; 16 patients diagnosed with MM and 16 healthy individuals served as control. All were subjected to history taking, clinical examination, routine laboratory investigations and leptin & resistin blood level. Laboratory investigations were done for diagnosis and staging for MM patients. RESULTS: Leptin was significantly higher in MM patients compared with the control group, unlike resistin which showed no significant difference between the two groups. A significant positive relation was found between IgG level & leptin. Similarly, a significant difference in leptin level has been observed between stage I & stage II (higher in II). CONCLUSIONS: Leptin may play a role in the pathogenesis of MM and its level may be changed in different stages.