Sanaa O. Abdallah

The role of microRNA-31 and microRNA-21 as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients

Abstract Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by familial aggregation and genetic predisposition. MicroRNAs (MiRNAs) serve as critical biomarkers in lupus patients because of their aberrant expression in different SLE stages. The study aimed to investigate the correlation of miR-31 and miR-21 with IL-2 in SLE patients as regulatory biomarkers in the activation of T lymphocytes of Egyptian lupus patients. Quantitative RT-PCR is carried out to estimate the expressions of miR-31 and miR-21, and IL-2 levels were determined using ELISA in plasma of 40 patients with SLE, 20 of their first-degree relatives and 20 healthy controls. The study also determined the systemic lupus erythematosus disease activity index (SLEDAI) score and proteinuria in SLE patients. The results revealed that miR-31 was lower expressed, while miR-21 was high expressed in SLE patients compared to their first-degree relatives and controls. MiR-31 was negatively correlated with SLEDAI and proteinuria in lupus patients, while miR-21 showed positive correlation with them. Also we found that there is a significant positive correlation between miR-31 and IL-2 in SLE patients, while miR-21 was negatively correlated with IL-2 level in patients. In conclusion, the study disclosed a significant association between miR-31 and miR-21 expression with IL-2 level in SLE patients. The regulatory biomarkers of miR-31 and miR-21 might have an impact on regulating IL-2 pathway expression and in turn on the activation of T lymphocytes in SLE.

Non-invasive predictive score of fibrosis stages in chronic hepatitis C patients based on epithelial membrane antigen in the blood in combination with routine laboratory markers

Aim:  The epithelial membrane antigen (EMA) could detect small deposits of liver malignant cells. However, no information exists regarding the use of EMA in patients with chronic hepatitis C (CHC). Therefore, we attempted to evaluate the diagnostic performance of EMA to distinguish patients with different liver fibrosis stages.

Perinatal transmission of hepatitis c antigens: envelope 1, envelope 2 and non-structural 4

Abstract Background: Perinatal exposure to hepatitis C virus (HCV) antigens during pregnancy may affect the developing immune system in the fetus. We aimed to study the perinatal transmission of HCV structural and non-structural antigens. Methods: Sera from 402 pregnant mothers were tested for anti-HCV antibody and HCV RNA. HCV antigens were determined in sera from 101 HCV-infected mothers and their cord blood. Results: In both serum and cord blood samples, HCV NS4 (non-structural 4) at 27 kDa, E1 (envelope 1) at 38 kDa and E2 (envelope 2) at 40 kDa were identified, purified and quantified using western blotting, electroelution and ELISA. Maternal sera and neonate cord blood samples had similar detection rates for NS4 (94.1%), E1 (90.1%) and E2 (90.1%). The mean maternal serum levels (optical density, OD) of HCV NS4 (0.87 ± 0.01), E1 (0.86 ± 0.01) and E2 (0.85 ± 0.01) did not differ significantly (p > 0.05) from those of neonatal cord blood (0.83 ± 0.01, 0.87 ± 0.01 and 0.85 ± 0.01, respectively). Also, strong correlations (p < 0.0001) were shown between sera and cord blood sample levels of HCV NS4, r = 0.77; E1, r = 0.76 and E2, r = 0.80. The vertical transmission of these antigens in vaginal delivery did not differ significantly (p > 0.05) from those in caesarean section. Conclusions: These findings indicate that vertical transmission of HCV NS4, E1 and E2 antigens was very high. Thus, exposure to these antigens may influence the developing immune responses to natural infection or future vaccination.

Combined use of epithelial membrane antigen and nuclear matrix protein 52 as sensitive biomarkers for detection of bladder cancer.

Background The advent of noninvasive urine-based markers as well as other novel modalities has yielded improved diagnostic accuracy. However, the new markers failed to reach higher sensitivity and specificity. We therefore evaluated the potential role of epithelial membrane antigen (EMA) and nuclear matrix protein 52 (NMP-52) singly and combined as noninvasive biomarkers for the detection of bladder cancer (BC). Methods A total of 160 individuals including 66 patients with BC, 54 patients with benign urologic disorders and 40 healthy volunteers were investigated. Urinary EMA at 130 kDa and NMP at 52 kDa were identified, purified and quantified by Western blot, electroelution and enzyme-linked immunosorbent assay (ELISA). The diagnostic performance of each biomarker and their combination were compared using area under receiver operating characteristic curves (AUC). Results Mean urinary EMA, 2.42 µg/mL, and NMP-52, 17.85 µg/mL, were significantly elevated in patients with BC compared to controls, 1.18 and 3.44 µg/mL, respectively (p<0.0001). The combined use of these markers yielded values which were increased 4.4- and 13.7-fold in the benign and malignant disease groups, respectively, with respect to the normal group. The values of EMA and NMP-52 were significantly higher in patients with higher-grade tumors than those with lower-grade tumors (p<0.0001). Moreover, this combination could predict all BC stages and grades with 0.91 AUC, 94% sensitivity and 80% specificity. Conclusions EMA and NMP-52 in combination could be promising noninvasive biomarkers for BC detection.

Clinical value of a diagnostic score for colon cancer based on serum CEA, CA19-9, cytokeratin-1 and mucin-1

Abstract Background: Although established markers such as CEA and CA19-9 are important for diagnosing early stages of colon cancer, they are not ideal. Developing promising markers include cytokeratin 1 (CK1) and mucin-1 (MUC1), but the combined value of each of these markers is unclear. We therefore evaluated the value of a combined laboratory-based score of these four markers in the diagnosis of colon cancer. Methods: Two hundred patients who had undergone colonoscopic examination (150 colon cancer, 50 benign growths) were recruited. The study was controlled by 35 healthy subjects. CEA, CA19-9, CK1 and MUC1 were measured by ELISA and evaluated for cancer diagnosis using area under the receiver operating characteristic curve (AUC). Results: Serum levels of all four markers were increased in the order colon cancer > benign disease > healthy controls (p < 0.001). In multivariate analysis, CA19.9 (p = 0.025), CK1 (p < 0.001) and MUC1 (p = 0.009) were significant independent predictors of colon cancer. A score that gave the greatest power of discrimination for colon cancer was defined as 1.06 + [0.001 × CA19.9 result] + [0.003 × CEA result] + [0.03 × CK1 result] + [0.05 × MUC1 result]. The colon score provided superior discrimination, AUC, and sensitivity and specificity for colon cancer versus benign growth than each of the individual markers. Similarly, the colon score provided superior AUC, and sensitivity and specificity that each individual marker for tumour stage, lymph node invasion and distant organ metastases than each individual marker. Conclusion: A colon score derived from serum CEA, CA19-9, CK1 and MUC1 is a potential valuable non-invasive index that could be used for detection and screening early stage colon cancer patients.