Assessment of donor specific IgG Anti-HLA subclasses before and after kidney transplantation in Upper Egypt: A Single Center Study.

Donor specific antibodies (DSAs) are known as the leading cause of antibody mediated rejection (AMR), graft loss in kidney transplant (KT) recipients. DSAs characteristics, as immunoglobulin (Ig) classes, subclasses, and strength, are important to assess the immunological risk, early prediction of AMR, and therefor proper management. This longitudinal, case control study included 32 KT recipients at Assiut University Urology Hospital and 10 age and sex matched normal subjects as the control group. Total IgG, its subclasses and anti-human leukocyte antigen (anti-HLA) panel reactive antibody (PRA) were detected pre-transplantation (pre-TX), at 6-12- and 24-36-months post-TX. Rejection occurred in 4 recipients, 3 of them had high total IgG, IgG1 and/or IgG3. IgG2 and IgG4 were normal in all recipients. There were preformed anti-DSAs antibodies in 3/32 recipients (9.4%). Of these, two recipients became negative with no rejection occurred. The third recipient had high post-TX mean fluorescence intensity (MFI) and AMR occurred. The pre-TX PRA was negative in 29/32 recipients (90.6%). The PRA was negative in 8/29 recipients (27.6%) and the remaining 21/29 recipients (72.4%) developed de novo DSAs post-TX (MFI < 3000->10000). Rejection occurred with both low and high MFI. In 11 recipients, anti-HLA class I and II were not different between pre-TX, 3-6- and 24-36 months post-TX with no rejection occurred. The frequency and median levels of total IgG, IgG1 and IgG3 were increased in all recipients 24-36 months post-TX when compared with their levels pre-TX and 6-12 months post-TX in the 11 recipients and with the control group. The graft survival time significantly decreased in recipients with positive post-TX class I PRA. In conclusion, preformed DSAs may persist post-TX or turn negative. De novo DSAs developed post-TX even in non-sensitized recipients. Serum total IgG, IgG1 and IgG3 frequency increase 2-3 years post-TX.

The Prognostic Value of Different Levels of Cortisol and High-Sensitivity C-Reactive Protein in Early Acute Pancreatitis.

BACKGROUND: Acute pancreatitis (AP) ranges in severity from mild to severe with high mortality. Severe AP, similar to other critical illnesses, is associated with changes in cortisol level. Early increase of high-sensitivity C-reactive protein (hs-CRP) as an inflammatory marker could be an indicator of AP progression. We aimed to assess the level of cortisol and hs-CRP on initial diagnosis of AP and identify their prognostic value. METHODS: This case-control study included patients with AP and a control group of healthy subjects. Laboratory tests such as liver profile, kidney functions, blood picture, lactate dehydrogenase, blood glucose, and lipogram were evaluated, the severity of AP was determined, the duration of hospitalization, complications, and outcomes were identified, and the serum levels of cortisol and hs-CRP were assessed. RESULTS: There were 90 patients with AP and 60 controls with a higher percent of females in both groups. Serum cortisol and hs-CRP were significantly higher in AP relative to controls and were higher in severe AP relative to mild AP. Significant positive correlation was present between high cortisol and severity of AP (r = 0.520 and p<0.001) and negatively with pancreatic necrosis (r= - 0.303 and p = 0.007) and morality (r= - 0.432, p = 0.005) while hs-CRP did not show significant correlation. CONCLUSIONS: Different levels of serum cortisol in early AP should be considered on initial diagnosis. High cortisol level was a good prognostic indicator for AP with low mortality. This could have further implications on the appropriate initiation of steroid therapy to prevent necrotizing pancreatitis and lower the mortality. Meanwhile, hs-CRP has a low prognostic value in early AP.

Prevalence of Zinc Transporter 8 Auto Antibodies among Newly Diagnosed Type 1 Diabetic Cases Admitted to Assiut University Children Hospital.

Type 1 diabetes mellitus (T1DM) remains the most common form of diabetes in childhood. The incidence of type 1 diabetes is continuously increased. Zinc transporter protein 8 antibodies (ZnT8A) measurement can be helpful in detection of suspected new cases of type 1diabetes when other islet auto antibodies are negative. We evaluated the role of ZnT8A in diagnosis of new cases of T1DM in comparison to islet cell antibody (ICA), and assessed its prediction value among siblings. 31 of newly diagnosed T1DM patients and 55 age and sex matched healthy siblings were included. Measurements of ZnT8A and ICA was carried out by ELISA. ZnT8A had 45% sensitivity and 69% specificity while ICA had 64.5% sensitivity and 83.64% specificity. 22.6% of diabetic patients had high level of ZnT8A as compared to 20% of siblings (P < 0.001 and P < 0.001, respectively). 28.6% of diabetic patients with high titer ZnT8A had positive ICA (P < 0.04) as compared to 63.6% in sibling group (P < 0.001). It is concluded that ZnT8A and ICA play an important role in diagnosis and prediction of T1DM cases.

Circulating osteocyte-related biomarkers (vitamin D, sclerostin, dickkopf-1), hepcidin, and oxidative stress markers in early breast cancer: Their impact in disease progression and outcome.

Breast cancer (BC) is a major concern to female health worldwide. We assessed the circulating osteocyte-related biomarkers, hepcidin, and oxidative stress status among early-stage BC patients in aspects of clinical severity and impact on the outcome. The study incorporated 73 patients categorized into 57 early-stage BC and 16 benign breast diseases and 30 healthy controls. Serum 25-hydroxyvitamin D [25(OH)D], sclerostin (SOST), dickkopf-1(DKK1), and hepcidin were measured using ELISA, while, serum oxidative stress markers were assessed by spectrophotometry. Our results show that patients with BC showed significant increase in the mean levels of DKK1, SOST, hepcidin, and LPER and significant decrease in the mean levels of 25(OH)D, SOD, GPx, and Hb when compared with controls and benign breast diseases. Significantly higher DKK1, hepcidin, and SOD levels among benign breast diseases were found in comparison to control group. There were significantly lower levels of 25(OH)D, SOD, and Hb and significantly higher levels of SOST, DKK1, hepcidin, No, and LPER with advanced grade. Lower levels of 25(OH)D, SOD and higher levels of SOST, hepcidin were observed with increasing the malignant stage. Reduced levels of 25(OH)D, and SOD were significantly associated with poor prognosis and were strong predictors among BC. There were significant negative correlations between 25(OH)D with LPER, SOST, and hepicidin. We conclude that low 25(OH)D, high SOST, DKK1, and hepcidin, and dysregulated oxidative stress could be helpful in early detection and assessment of BC. 25(OH)D, and SOD were the most relevant to tumor progression and prognosis which indicate a significant role in the BC pathogenesis and could be promising targets in management. Our research paves the way to disrupt vicious circle between these biomarkers to obtain the best care of BC.

Impact of the etiology and Vitamin D receptor TaqI rs731236 gene polymorphism on the severity of acute pancreatitis.

BACKGROUND/PURPOSE: This work aimed to assess the impact of different etiologies of acute pancreatitis (AP) and vitamin D receptor (VDR) TaqI rs731236 gene polymorphism on the severity of AP. METHODS: This case-control study included 70 patients with AP and 40 healthy controls. Etiologies of AP were identified by imaging, ANA, cytomegalovirus (CMV) IgM, coxsackie B virus IgM, and IgG4. Genotyping of VDR TaqI rs731236 polymorphism, Laboratory tests and severity scores using Ranson, BISAP, Atlanta and APACHE II scores were determined. RESULTS: The age in AP patients was 36.03 ± 10.76, and females were 85.7%. The etiologies of AP were as follows: biliary (51.4%), coxsackievirus (22.9%), autoimmune (14.3%), post-ERCP (8.6%) and 2.9% were idiopathic. The TT genotype of VDR polymorphism was significantly more common in AP than control (P = .001) and allele T dominated in AP group (OR = 2; 95% CI: 0.665-5.64). Most cases showed low severity scores with significant differences among etiologies and VDR genotypes. Biliary pancreatitis showed highest percentages of severe AP. However, etiologies and VDR polymorphism were not predictors of severity. CONCLUSION: Etiology of AP could have impact on the disease severity. VDR gene polymorphism increases the risk of AP. Neither the etiology nor VDR gene polymorphism could predict AP severity.

Glypican-3 and Melanoma Antigen Genes 1 and 3 as Tumor Markers for Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the commonest liver cancer; its incidence and prevalence are continuously increased. Glypican3 (GPC3), melanoma antigen-1, 3 genes (MAGE1 and 3) are tumor markers used in HCC. We evaluated their role in HCC detection and assessed their relation to tumor parameters. Three groups, HCC group, liver cirrhosis group and a control group were studied. AFP, GPC3, and MAGE1 and 3 mRNA were determined in all study subjects. Tissue GPC3 was examined in patients with HCC only. Serum AFP and GPC3 were elevated in HCC group compared to other groups (P < 0.000 and P < 0.001, respectively). AFP at cutoff 44.4ng/ml and GPC3 at cutoff 5.6µg/L resulted in 81% and 90.1% sensitivity, 73.3% and 92.6% specificity, respectively. The combined measurement of both increased the sensitivity and the specificity to 100% and 93.3%, respectively. GPC 3 was detected in tissues of 81.0% of the cases. MAGE-1 and MAGE-3 genes expression were detected in 61.9% and 52.4%, respectively in HCC cases but not in other groups. GPC3, MAGE1and 3 were increased with advanced tumor stage, size, and nodule numbers. We concluded that GPC3 is a promising diagnostic marker for HCC, and MAGE 1 and 3 could be helpful in early detection of extrahepatic metastasis of HCC.