Elrefaei, Mohamed

HLA‐C*03:648 differs from HLA‐C*03:04:02 by one nucleotide substitution at Codon ‐23 (CGG > CTG) in exon 1.

HLA‐B*57:168 differs from HLA‐B*57:01:01:01 by one nucleotide substitution at codon 325 (TGC > TCC) in exon 7.

Abstract Hepatocellular carcinoma (HCC) is the most common primary malignant tumor of the liver. This study aimed to assess serum hTERT level and its relation to the progression of liver disease. Also, it aimed to assess the effect of HCV core protein on memory T-cells in HCV patients with or without HCC, and the correlation between memory cells phenotype and the progression of the disease in the same patients. hTERT level in serum was assessed through relative quantitative RT-PCR. Flow cytometric analysis was used to assess T-cells responsiveness (as IFN-γ secretion) before and after stimulation with HCV core protein, and memory CD8+ cells phenotype using several differentiation markers. hTERT was found to be increased in a stepwise manner upon comparing its level in controls, chronic hepatitis patients, cirrhotic patients, and HCC patients. T-cells showed a similar manner of stepwise decrease in response (decreased IFN-γ secretion) in HCC patients compared to HCV patients without HCC and controls. Also, late differentiated memory cells (CD8+ CD27- CD28- CD45RA+CCR7-) were depleted in HCC patients compared to HCV patients without HCC. In conclusion, these results suggest a negative correlation between hTERT and IFN-γ secretion by T- cells in HCV patients and that this relationship along with the depletion of late differentiated memory cells could help the progression of liver disease to HCC.

AbstractBackgroundHistologic acute graft pyelonephritis (HAGPN) after kidney transplantation (KT) has been assessed less frequently than urinary tract infections (UTIs) or clinical acute graft pyelonephritis. Risk factors for HAGPN, its association with graft loss, and measures that might prevent it are not known.MethodsWe performed a retrospective review of HAGPN cases identified from KT occurring between January 2008 and December 2017 at our institution. We compared the HAGPN cases to a randomly selected control group of KTs to identify risk factors using univariate and multivariate Cox regression models. The association between HAGPN and graft loss was also assessed, similarly.ResultsHAGPN was identified in 46 of 1391 patients (cumulative incidence, 5% [95% CI, 3%–7%]) undergoing KT at a single center from January 2008 through December 2017 (median time to diagnosis, 241 days after KT; interquartile range, 122–755 days). Indications for biopsy were follow‐up of treated rejection (n = 20 [43%]), KT protocol biopsy (n = 19 [41%]), and acute kidney injury (n = 7 [15%]). Histologic rejection, UTI, and asymptomatic bacteriuria (ASB) were present in 23 (50%), 9 (20%), and 16 (35%). Multivariate Cox proportional hazards models comparing KT recipients with or without HAGPN (n = 46 and n = 138, respectively) showed that HAGPN was associated with urologic complication by day 30, delayed graft function, previous UTI or ASB, and a history of rejection. In the univariate and multivariate analyses, HAGPN was associated with an increased risk of graft loss.ConclusionHAGPN is an infrequent, unanticipated, and clinically significant complication of KT.

AbstractPurposeInduction immunosuppression has improved the long‐term outcomes after lung transplant. This is the first report exploring the association of induction immunosuppression with the development of de novo donor‐specific human leukocyte antigen (HLA) antibodies (DSA) in lung transplant recipients (LTR).MethodsSixty‐seven consecutive primary LTR were followed for 3 years posttransplant. A total of 41/67 (61%) LTR‐received induction immunosuppression using a single dose of rabbit Antithymocyte Globulin (rATG; 1.5 mg/kg) within 24 h of transplant. All recipients had a negative flow cytometry crossmatch on the day of transplant. Serum samples at 1, 3, 6, and 12 months posttransplant were assessed for the presence of de novo HLA DSA.ResultsDe novo HLA DSA were detected in 22/67 (32.8%) LTR within 1‐year posttransplant. Of these, 9/41 (21.9%) occurred in the induction therapy group and 13/26 (50%) in the noninduction group. Class II DSA were detected in 3/41 (7.3%) LTR who received induction compared to 9/26 (34.6%) LTR without induction immunosuppression (p = .005). Differences in overall survival or freedom from chronic lung allograft dysfunction rates between the two groups were not statistically significant.ConclusionInduction immunosuppression utilizing a modified regimen of single‐dose rATG is associated with a significant reduction in de novo DSA production in LTR.

Numerous risk factors for breast cancer (BC) have been identified. High-risk human papilloma virus (HR-HPV) is the etiological agent of cervical cancer and in some cases of head and neck cancer, specifically oropharyngeal cancer, but the role of HR-HPV in evoking neoplasia in BC is still unclear. In this study, all women above the age of 18 visiting the oncology clinic at Al-Azhar university hospital and Ain Shams specialized hospital between the period of February 2017 and March 2018 were invited to participate. We determined the prevalence of HR-HPV genotypes 16, 18, and 31 in breast tissue samples from 72 women with treatment-naïve BC and 15 women with benign breast lesions (BBL) by quantitative real-time PCR (qRT-PCR) and primer sets targeting the E6 and E7 regions. High-risk human papilloma virus DNA was detected in 16 of 72 (22.2%) BC cases (viral load range = 0.3-237.8 copies/uL) and 0 of 15 women with BBL. High-risk human papilloma virus was detected in 14 of 16 (87.5%), 2 of 16 (12.5%), and 0 of 16 (0%) for genotypes 16, 18, and 31, respectively. Forty-three age-matched healthy Egyptian women were enrolled as controls for assessment of local risk factors that can be used to initiate a strategy of BC prevention in Egypt. Assessment of the risk factors demonstrated that low education level, passive smoking, lack of physical activity, family history of cancer, and use of oral contraception were significant risk factors for BC. In conclusion, our results lead us to postulate that HR-HPV infection may be implicated in the development of some types of BC in Egyptian women. In addition, identification of local risk factors can support practical prevention strategies for BC in Egypt.

Abstract Background Histologic acute graft pyelonephritis (HAGPN) is a complication of kidney transplantation (KT) diagnosed serendipitously by renal biopsy. A retrospective review of 1391 patients who underwent KT at our institution between 2008 and 2017 identified 46 cases (cumulative incidence 5%). Rejection was present in 50% of biopsies demonstrating HAGPN, complicating management. The aims of this study were to identify risk factors and outcomes of HAGPN. Methods Recipient, donor, operative and post-transplant characteristics of 46 cases of HAGPN and 138 controls randomly selected from the 1345 patients who underwent KT between 2008 and 2017 were assessed in univariable and multivariable Cox regression models. Associations of HAGPN with death or graft failure were assessed in univariable models. Results In univariable analysis, characteristics associated with increased risk of HAGPN in order of decreasing hazard ratio (HR) were rejection (HR 10.82, 5.66-20.72), urinary tract infections (UTI) or asymptomatic bacteriuria (ASB) (HR 6.28, 3.43-11.50), urologic malfunction (UM) within 30 days of KT, (HR 5.34, 2.85-10.02), less than 4 matches at HLA A/B/DR loci (HR 3.74, 1.19-11.76), delayed graft function (DGF) (HR 2.1, 1.47-3.00), basiliximab induction (HR 1.59, 1.05-2.42), diabetes mellitus (DM) at KT (HR 1.52, 1.07-2.16), operative time (HR 1.11, 1.03-1.19) and cold ischemic time (CIT) (HR 1.05, 1.02-1.06). UM, rejection and UTI or ASB were the most significant risk factors based on clinical and statistical importance, and after adjusting for them, DM, transplant type, CIT, ureteral stent placement and DGF remained significant risk factors. In univariable analysis, ureteral stent placement at transplant (HR 0.60, 0.43-0.88) and living-related donor (HR 0.18, 0.04-0.78) were each associated with reduced risk of HAGPN which persisted after multivariable analysis. In univariable analysis, HAGPN was associated with death (HR 17.04, 7.93-39.31) and graft failure (HR 3.77, 1.73, 8.20). Conclusion HAGPN is an infrequent, unanticipated, clinically significant complication of renal transplantation. Post-transplant dysfunction of the allograft collection system may be a modifiable risk factor. Disclosures All Authors: No reported disclosures

Several subsets of regulatory CD4+ T cells (CD4+ Tregs) have been described in peripheral blood and tumor microenvironment of breast cancer (BC) patients and may play a role in the progression of BC. High-risk human papilloma virus (HR-HPV) has a causal role in cervical, head, and neck tumors but the role of HR-HPV in evoking neoplasia in BC is still unclear. In this study we assessed the prevalence of CD4+CD25+ FOXP3+ regulatory T cells (CD4+Tregs) and CD3+ CD8+ T cells by flow cytometry in peripheral blood from a total of 55 Egyptian women, including 20 treatment-naïve BC, 15 with breast benign lesions (BBL), and 20 healthy volunteers (HV). HR-HPV genotypes type 16, 18, and 31 were investigated in breast tissue from all BC and BBL patients using Real-Time PCR. HR-HPV was detected in 4/20 (20%) and 0/15 (0%) BC and BBL patients respectively. The frequency of CD4+ Tregs was significantly higher in BC compared to BBL and HV, ( P < 0.001). In addition, we observed a significantly higher frequency of CD3+ CD8+ T cells in peripheral blood of patients with late stage III BC compared to early stage I and II BC ( P = 0.011). However, there was no significant association between the ratio of CD8+ T cell to CD4+ Tregs frequencies and the expression of Estrogen Receptor (ER), Progesterone Receptor (PR), and Human Epidermal Growth Factor Receptor 2 (HER2). These results lead us to postulate that the association between the frequency of CD4+ Tregs and CD8+ T cells in the peripheral blood may be a prognostic or predictive parameter in Egyptian women with BC. In addition, HR-HPV infection may be implicated in the development of some types of BC in Egyptian women.