This study reports for the first time a quantitative proteome analysis for PMP from patients with HCV-induced cirrhosis and HCC. Data are available via ProteomeXchange with identifier PXD005777.

a faculty of medicine, department of clinical Pathology, alexandria university, alexandria, egypt; b chru de montpellier and université de montpellier, irmB, laboratoire de Biochimie Protéomique clinique, montpellier, france; c faculty of medicine, department of neuropsychiatry, alexandria university, alexandria, egypt; d faculty of medicine, department of anesthesia and surgical care, alexandria university, alexandria, egypt ABSTRACT Background: Multiple sclerosis (MS) is a highly heterogeneous disease affecting the central nervous system (CNS). Cerebrospinal fluid (CSF) has been preferred over other body fluids when studying this disease since it is the closest sample related to MS pathological changes. The aim of this study was to investigate differences of CSF protein expression in MS patients by twodimensional polyacrylamide gel electrophoresis (2-DE) in order to identify candidate biomarkers with potential clinical utility. Methods: We analysed the CSF protein expression of seven remitting-relapsing MS patients and seven control subjects using 2-DE. As a complementary step, the CSF of patients was pooled and compared to control-pooled CSF using 2-DE in order to minimise the inter-individual variations. Statistically significant spots were identified by mass spectrometry. Results: In the analysis of the individual samples, a consistent up-regulation of four statistically significant spots was noticed in the CSF of the patients. In the analysis of the pooled samples, 4 spots were up-regulated in the control pool, while 12 spots were up-regulated in the patient pool. Using matrix-assisted laser desorption ionisation with two time of lights (MALDI-TOF/TOF), we did not yield any results for the identification of proteins but with liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), we were able to reach the identity of four proteins which were alpha-1-antichymotrypsin, prostaglandin-H2 D-isomerase, desmoplakin and hornerin. Conclusion:The results of this study support the presence of changes in the CSF proteome of MS patients. There is a need to investigate the role of these candidate CSF spots in a larger number of MS patients.

To assess the possible association between the protein tyrosine phosphatases non-receptor 22 (PTPN22) gene 1858 CT polymorphism and the predisposition to systemic lupus erythematosus (SLE) in Egyptian patients and its influence on clinical and laboratory parameters. PTPN22 gene 1858 CT polymorphisms were analyzed in forty SLE patients and 20 normal controls by real-time polymerase chain reaction (PCR) technology, using the TaqMan 5-allele discrimination assay. Detailed history, clinical examination, and investigations were done to detect various organ involvement. The homozygous genotype TT was absent in both SLE and controls. The CC genotype was observed in 47.5% SLE and 80% controls; the CT genotype was found in 52.5% patients and 20% controls. The frequencies of the C and T alleles were 74 and 26% in SLE and 90 and 10% in controls, respectively. The presence of CT genotype increased the risk for developing SLE by 4.42. Renal involvement was significantly higher in SLE patients with CT (76.2%) compared to those with CC genotype (42.1%).

Advances in immunosuppressive therapy allowed renal transplantation to become the treatment of choice for suitable candidates with (end stage renal disease) ESRD. The post-transplant therapeutic strategy is difficult due to narrow therapeutic indices for the currently used immunosuppressive drugs. Inter-individual differences in drug bioavailability are related to genetic and non genetic factors. The idea of targeted and personalized therapy is to achieve therapeutic success. The empirical dose has lost its value in the post-transplant therapy and an individualized dosage regimen must be established. Interindividual heterogeneity in expression of ABCB1 and CYP3A4 has been suspected to be one of the factors resulting in cyclosporine (CsA) pharmacokinetic variation. This study aimed to investigate the impact of inter-individual CYP3A4 rs4646437C>T and MDR1 G2677T/A polymorphisms on cyclosporine dose requirements among a sample of renal transplant Egyptian recipients. Fifty adult Egyptian patients on CsA were genotyped for CYP3A4 rs4646437C>T and MDR1 G2677T/A and correlated with CsA dose requirement and dose-adjusted CsA (C0) blood levels at 3, 6, and 9 months post transplantation. CYP3A4 rs4646437C>T influenced significantly cyclosporine kinetics, the T carriers requiring higher cyclosporine dose. Daily dose requirements were also significantly higher in T allele MDR1 2677G>T GG genotype as compared to GT/TT genotypes at 3, 6, and 9 months post transplantation. Genotyping of both CYP3A4 and MDR1 SNPs may be helpful in providing pre-transplant pharmacogenetic information to individualize CsA dosing. Heterozygous CT genotype is the most frequent CYP3A4 rs4646437C>T genotype in the studied group of Egyptian population (48 %) followed by CC genotype and TT genotype. Daily dose requirements were significantly higher in T allele MDR1 2677G>T GG genotype as compared to GT/TT genotypes at 3, 6, and 9 months post transplantation.

Sickle cell haemoglobinopathy is a genetic disorder caused by the presence of haemoglobin S (HbS) including sickle cell disease (SCD) (sickle cell anemia, HbS/β -thalassaemia and HbSC disease) and sickle cell trait. In Siwa Oasis, most remote oasis town in Egypt, the prevalence rate of sickle cell haemoglobinopathy is approaching 20%. The 1 polymorphism was reported to increase the HbF level ameliorating the severity of the SCD. The present study aims mainly to investigate the genotype frequency of -158Gγ (C→T) Xmn1 polymorphism in Siwa Oasis, Egypt and to study, if possible, any association with increased HbF expression. This study was performed on 62 sickle cell carriers (AS), three cases of sickle cell anaemia (SS) detected during a screening programme conducted on primary school children in Siwa Oasis by Alexandria Faculty of Medicine in 2011-2012. Sixty-five age-matched and sex-matched healthy controls (AA) were included. All enrolled children were subjected to PCR-RFLP for the detection of -158Gγ (C→T) Xmn1 polymorphism using the Xmn1 restriction enzyme. Genotyping of the -158Gγ (CvT) Xmn1 polymorphism revealed that among AS, 85.5% were homozygous for the wild-type allele (CC) and 14.5% were heterozygous (CT). However, among SS, two cases were homozygous for the wild-type allele (CC) and one case was heterozygous (CT). The genotype frequencies among AA were 83.1% homozygous for the wild-type allele (CC) and 16.9% heterozygous (CT). None of the studied cases or controls was homozygous for the mutant allele (TT). Among both AS and AA, there was no significant difference between the wild-type and heterozygous genotypes regarding HbF level. Studying genotype frequency of the1 γG globin polymorphism (-158C>T ) in Siwa Oasis, Egypt can be considered as a starting point for further research targeting this community sector. However, in our studied cohort, there were only three sickle cell anaemia patients. Further, none of the tested cases or controls was found to be homozygous for the mutant allele (TT). In the absence of any homozygous genotype for the mutant allele (TT) in the studied cohort, any reasonable conclusion on the effect of polymorphism on increase in HbF could not be established. Further studies with a larger sample size are needed for better understanding of the possible association.