Interleukin 16 polymorphism and susceptibility of rheumatoid arthritis disease in Egyptian population.

Rheumatoid arthritis (RA) is a systemic and multiple-stage disorder characterized by chronic inflammation with extensive synovitis. The genetic and environmental factors are associated with the risk for RA development. In RA, the induced IL-16 may play a role in initiating, sustaining and increasing the inflammatory response and development of synovitis, nevertheless IL-16's actual role in RA pathogenesis must be studied further. This study intended to investigate the association of IL-16 gene polymorphism and RA disease, to determine the genetic role of IL-16 polymorphism and predict the risk of RA development and clinical disease activity. One hundred and Fifty RA patients and 150 apparently healthy control subjects were included in this case-control study. RA disease activity and functional status were evaluated for all RA patients. IL-16 gene polymorphism (SNP rs11556218 T/G) was genotyped using real-time polymerase chain reaction. The difference in IL-16 (rs11556218 T/G) genotype frequencies between RA patients and controls was not statistically significant. However, the G allele was frequently presented in RA patients as compared to controls (p=0.047). Moreover, G allele carriers had two times more risk to develop RA disease than T allele carriers (OR=2.598; 95%CI=1.078-6.825) with dominant genetic association. Alternatively, the G/G genotype was associated with high CDAI, RADAS-5 and HAQ disability index in comparing to other genotypes (T/T-T/G). In conclusion, there was an association between allele G of IL-16 polymorphism (rs11556218 T/G) and risk of RA disease development. In addition, there was an association between genotype G/G and increased clinical disease activity and health disability.

Biochemical Analysis of C-X-C Motif Chemokine Ligand 10 (CXCL10) as a Biomarker in Patients with Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is characterized by chronic inflammation and synovial hyperplasia that eventually leads to the destruction of the joints. CXCL10 has been originally identified as a pro-inflammatory chemokine that mediate leukocyte trafficking and modulate innate and adaptive immune responses. It plays a critical role in the inflammatory response and is involved in several biological processes. The aim of the study was to assess the diagnostic efficacy of serum CXCL10 levels in early RA patients. Patients and methods: The study included 60 RA patients; 30 of them were early diagnosed, and 30 longstanding RA and 30 healthy controls. Clinical examination was done for all patients. Measurement of serum CXCL10 level was done by ELISA, while assessment of disease activity in patients was done using disease activity score (DAS-28). Serum levels of CXCL10 were significantly higher in RA patients than controls (P < 0.001), and was more elevated in early diagnosed than longstanding RA patients, with a a significant positive correlation with DAS-28 ESR (r=0.361, P=0.005), number of tender joint (r=0.319, P=0.013), and number of swollen joint (r=0.280, P=0.030). A cutoff at 470.0 pg/ml was able to recognize longstanding RA with a sensitivity of 88.3% and a specificity of 90% , while a cutoff of 793 pg/ml was able to diagnose early RA with 65% sensitivity and 77% specificity (P=0.009). in conclusion, serum CXCL10 may be a useful biomarker for diagnosis of early RA and determination of disease activity.

25-hydroxyvitamin D Deficiency and Predictive Factors in Patients with Diabetic Nephropathy in Type 2 Diabetes Mellitus.

Diabetes mellitus is a metabolic disease that is characterized by chronic hyperglycemia. Type 2 diabetes is a global health problem and leading to many dangerous complications. Diabetic nephropathy is a significant microvascular complication resulting from diabetes mellitus that is affecting up to 50% of patients with end stage renal disease. Vitamin D deficiency may occur due to many different factors and is associated with many serious diseases as diabetic nephropathy. To investigate the 25-hydroxyvitamin D deficiency and predictive factors in patients with diabetic nephropathy in type 2 diabetes mellitus. One hundred type 2diabetic patients were divided into two groups according to Alb/creat ratio to diabetic patients with and without nephropathy and 50 non-diabetic controls. We measured the serum 25-hydroxyvitamin D levels in all the study populations. The mean serum level of 25 (OH) D was significantly decreased in patients with diabetic nephropathy (13.41±4.99 ng/ml, P=0.002). There was a significant correlation with vitamin D deficiency and the patients residency and also a significant positive correlation with eGFR (r = 0.317, P = 0.025) and a significant negative correlation with Alb/creat Ratio(r = -0.323, P = 0.022). The significant best-fitting predictors of vitamin D deficiency were living in rural area (OR=4.030, P < 0.021) and eGFR < 60 (OR=5.412, P < 0.034). In conclusion, vitamin D deficiency is prevalent in patients with diabetic nephropathy living in rural areas. Low eGFR < 60, Alb/creat ratio more than 30 mg/24h and HbA1c > 9 could be considered as predictive factors of vitamin D deficiency in these patients.

Clinical significance of suppressor of cytokines signalling-3 mRNA expression from patients with non-Hodgkin lymphoma under chemotherapy.

INTRODUCTION: To date, little is known about blood immune marker changes that may be related to the development of Non Hodgkin Lymphoma (NHL) and treatment response with few serum biomarkers that could be useful in follow- up of the patients. OBJECTIVE: To quantify the expression of suppressor of cytokine signalling-3-(SOCS-3) gene at the mRNA level in the peripheral blood of patients with NHL and correlate with clinical pathological features and response to treatment. METHODS: Thirty patients with NHL and 20 healthy controls were enrolled in the study. The SOCS-3 mRNA level in peripheral blood (PB) was detected by semi-quantitative real-time polymerase chain reaction. Quantification of cytokines such as interleukin 6 and tumour necrosis factor alpha (IL-6 & TNF-α) were performed using sandwich enzyme-linked immunosorbent assays (ELISA). RESULTS: Increased expression of SOCS-3 mRNA in peripheral blood plus increased serum levels of IL-6 and TNF alpha from NHL cases with no complete remission after therapy. Higher levels of expression of SOCS-3 are associated with advanced disease, bone marrow involvement, extranodal involvement, poor performance status, B cell symptoms (fever, night sweats and weight loss) and high serum lactate dehydrogenase level which are evaluated by international prognostic index (IPI). Complete responses occur in 60% of patients with normal expression of SOCS-3 gene. Increased expression of SOCS-3 is common in diffuse large B cell lymphoma, CLL/small lymphocytic B cell lymphoma and follicular lymphoma. CONCLUSIONS: Over-expression of SOCS-3 mRNA from peripheral blood of NHL patients correlates with advanced disease and poor response to treatment. SOCS-3 mRNA expression in peripheral blood from NHL patients might be used to monitor response during treatment.