The immune system in neurological diseases: What innate-like T cells have to say.

The immune system classically consists of 2 lines of defense, innate and adaptive, both of which interact with one another effectively to protect us against any pathogenic threats. Importantly, there is a diverse subset of cells known as innate-like T cells that act as a bridge between the innate and adaptive immune systems and are pivotal players in eliciting inflammatory immune responses. A growing body of evidence has demonstrated the regulatory impact of these innate-like T cells in central nervous system (CNS) diseases and that such immune cells can traffic into the brain in multiple pathological conditions, which can be typically attributed to the breakdown of the blood-brain barrier. However, until now, it has been poorly understood whether innate-like T cells have direct protective or causative properties, particularly in CNS diseases. Therefore, in this review, our attention is focused on discussing the critical roles of 3 unique subsets of unconventional T cells, namely, natural killer T cells, γδ T cells, and mucosal-associated invariant T cells, in the context of CNS diseases, disorders, and injuries and how the interplay of these immune cells modulates CNS pathology, in an attempt to gain a better understanding of their complex functions.

Differentiation of Bone Marrow: Derived Mesenchymal Stem Cells into Hepatocyte-like Cells.

Cirrhosis is the end-stage liver fibrosis, whereby normal liver architecture is disrupted by fibrotic bands, parenchymal nodules and vascular distortion. Portal hypertension and hepatocyte dysfunction are the end results and give rise to major systemic complications and premature death. Mesenchymal stem cells (MSC) have the capacity of self-renew and to give rise to cells of various lineages, so MSC can be isolated from bone marrow (BM) and induced to differentiate into hepatocyte-like cells. MSC were induced to differentiate into hepatocyte-like cells by hepatotic growth factor (HGF) and fibroblast growth factor-4 (FGF-4). Differentiated cells were examined for the expression of hepatocyte-specific markers and hepatocyte functions. MSC were isolated. Flow cytometry analysis showed that they expressed the MSC-specific markers, reverse transcriptase-polymerase chain reaction (RT-PCR) demonstrated that MSC expressed the hepatocyte-specific marker cytokeratin 18 (CK-18) following hepatocyte induction. This study demonstrates that BM-derived-MSC can differentiate into functional hepatocyte-like cells following the induction of HGF and FGF-4. MSC can serve as a favorable cell source for tissue engineering in the treatment of liver disease.

BAALC and ERG Expression in Egyptian Patients with Acute Myeloid Leukemia, Relation to Survival and Response to Treatment.

AIM: Aim was to detect Brain and Acute Leukemia, Cytoplasmic (BAALC) and ETS-related gene (ERG) expression in patients with acute myeloid leukemia (AML) as well as to study their biologic and prognostic impact on the disease outcome and survival. PATIENTS AND METHODS: The current study was carried out on 44 patients with denovo acute myeloid leukemia, as well as 44 age and sex matched controls. The quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was performed for estimation of BAALC and ERG expression. RESULTS: The current study was carried out on 44 patients with denovo acute myeloid leukemia, as well as 44 age and sex matched controls. The quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR) assay was performed for estimation of BAALC and ERG expression. BAALC was expressed in 36 (81.82%) of AML cases versus 10 (22.72%) of the control group which was highly statistically significant (P < 0.001). While ERG was positive in 39(88.64%) of cases and 8(18.18 %) of controls and that was also highly statistically significant (P < 0.001). CONCLUSION: Further researches still needed to clarify the role of BAALC and ERG in the pathogenesis of leukemia and their importance as targets for treatment of AML.

Study of prognostic significance of marrow angiogenesis assessment in patients with de novo acute leukemia.

BACKGROUND: Angiogenesis is the highly ordered formation of new blood vessels from pre-existing vessels. It is seen throughout growth, in wound healing, menses, and is important in cancer, where pro- and antiangiogenic signals can be released by cancer cells, endothelial cells, stromal cells, blood, and the extracellular matrix. Aim of the study is to use standardized method for counting blood vessels to verify the significance and prognostic value of assessing marrow angiogenesis at diagnosis of de novo acute leukemia. SUBJECTS AND METHODS: The study included 70 newly diagnosed acute leukemia cases and a control group composed of 35 bone marrow biopsy sections obtained from breast cancer patients. Examination of CD34 immunohistochemically stained sections for the assessment of marrow angiogenesis by quantification of its microvessel density (MVD). RESULTS: MVD was significantly increased in acute leukemia patients in comparison to control group (P-value <0.001). Increased MVD was associated with unfavorable outcome. CONCLUSION: The study demonstrated an evidence of increased angiogenesis in acute leukemia detected by high bone marrow MVD which may play a significant role in leukemic process. Understanding its role may help in designing new therapeutic strategies for acute leukemia.

Prevalence of coagulation factor XIII and plasminogen activator inhibitor-1 gene polymorphisms among Egyptian women suffering from unexplained primary recurrent miscarriage.

Recurrent miscarriage (RM) is an obstetric challenge. Polymorphisms of factor XIII (FXIII) and plasminogen activator inhibitor-1 (PAI-1) may cause an imbalance between coagulation and fibrinolysis that can end in RM. The aim of the work was to determine the prevalence of FXIII Val34Leu and PAI-1 4G/5G gene polymorphisms in Egyptian women presenting with unexplained primary first trimester RM. Genotyping of 120 unexplained primary first trimester RM patients and 130 healthy controls by polymerase chain reaction (PCR) amplification of target genes followed by the allele-specific restriction enzyme digestion (RFLP technique). Among the cases, 67.5% of individuals had wild-type FXIII; 21.7% were heterozygous and 10.8% were homozygous for the FXIII Val34Leu polymorphism. Among controls, the proportions were 89.2%, 8.5% and 2.3% respectively. In addition, comparison between the two groups regarding Leu and 4G allele frequencies showed statistically significant differences (P values=0.0001 and 0.027 respectively). RM is more frequent in women with combined polymorphisms than in women with a single gene polymorphism (RR=3.91; OR=4.51; 95% CI=1.79-11.38; P=0.002). FXIII Val34Leu and PAI-1 4G/5G polymorphisms are prevalent in Egyptian women, with unexplained primary first trimester RM and combined polymorphisms statistically increasing the risk.

Immunoregulatory cytokines gene polymorphisms in Egyptian patients affected with acquired aplastic anemia.

The immune system is thought to play an important role in aplastic anemia (AA) in light of recent findings of hematologic reconstitution after immunosuppressive therapy. T cell activation, apoptosis, and the cytokines interferon- and TNF-α are suspected to play a role in the suppression of growth of progenitor cells and induced apoptosis in CD34 target cells, TGFß is a multifunctional peptide, usually produced in latent form and requiring activation to produce a biological response. Also, TGF-ß1 has been described as an important negative regulator of haemopoiesis. Over production of IL-6 is described in AA but is of unknown pathophysiological significance. To investigate the role of cytokine gene polymorphisms (IL-6/-174, TNF-α/-308, IFN-γ/+874, and TGFß1/-509) in patients with acquired AA to assess if genotypes associated with higher or lower production were more prevalent than in established control population and to study the possible association of these genotypes with the disease severity. Fifty AA patients were included in this study. Polymerase chain reaction-amplification refractory mutation system (PCR-ARMS) technique was used to detect INF-γ single nucleotide polymorphism -874A/T, and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to assess IL-6-174 C/G, TNF-α-308G/A, and TGFb1-509C/T gene polymorphisms. Genotypes associated with high production of TNF-α, TGF-ß and IFN-γ, and IL-6 were more frequent in patients than in control; no association was found between the presence of hypersecretory genotypes and the disease severity.

CD200 expression in B-cell chronic lymphoproliferative disorders.

BACKGROUND: Flow cytometry immunophenotyping (FCIP) is used for rapid, specific diagnosis of B-chronic lymphoproliferative disorders (BCLPDs). However, cases may deviate from the typical immunophenotype; therefore, there is a need for adding new marker(s) for differentiating BCLPDs.Lately, few researches highlighted CD200 expression in some BCLPDs. Our aim was to evaluate CD200 expression in different BCLPDs and whether adding CD200 to BCLPD-FCIP routine panels could improve the ability of their differential diagnosis. METHODS: We evaluated CD200 expression in 49 BCLPD patients and 26 age- and sex-matched control subjects. Flow cytometry immunophenotyping first panel included CD5, CD19, sIg, CD23, CD22, CD79b, and FMC7; for BCLPDs other than chronic lymphocytic leukemia (CLL) and mantle cell lymphoma, CD11c, CD103, CD25, and CD10 were evaluated. RESULTS: Using tricolor FCIP, CD200 showed high bright expression on CD5/19-positive clone in all B-CLL patients (100%), with a mean of 94% (SD, 11%); in the 2 cases of hairy cell leukemia, CD200 was brightly expressed on 96% and 99% of cells. In all other BCLPDs including mantle cell lymphoma, follicular lymphoma and splenic marginal zone lymphoma, CD200 expression (on CD19/22-positive cells) was less than 20% with a mean of 10% (SD, 8%) and a dim pattern. CD200 expression was significantly higher in CLL compared with non-Hodgkin lymphoma groups (P < 0.001). CONCLUSIONS: Evaluating CD200 expression has a great impact on accurate BCLPDs diagnosis and could be added to the BCLPD routine panels. The high expression of CD200 in B-cell CLL and hairy cell leukemia could open the option for targeted immune (anti-CD200) therapy.

Association between the monocyte chemoattractant protein-1 -2518G/A gene polymorphism and acute myocardial infarction patients among Egyptian population.

The aim of the present study was to investigate the possible association between the -2518G/A polymorphism of the monocyte chemoattractant protein-1 (MCP-1) gene and acute myocardial infarction (MI) in a sample of the Egyptian population. A total of 30 Egyptian patients with coronary artery disease (CAD) manifested as acute myocardial infarction (MI) for the first time and 25 unrelated healthy control individuals were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The proportion of G/A and G/G genotypes were significantly higher in the acute MI group than the control group (P < 0.05). The acute MI patients group showed a significant higher frequency of the G allele compared to the controls (P < 0.05). Analysis of the relationship between the G/A, G/G genotypes and A/A genotype acute MI group regarding the conventional risk factors showed statistical significant difference regarding age, total cholesterol, low-density lipoprotein and high-density lipoprotein (P < 0.05), but there was no significant relationship regarding sex, smoking, history of diabetes mellitus, hypertension, obesity, body mass index (BMI) and triglyceride, but we observed that the percentage of men was higher than the percentage of women in both G/A, G/G genotypes and A/A genotype acute MI patients. Also, among our patients, the percentage of smokers, diabetics, hypertensive, and obesity and the mean of BMI and triglyceride were higher in the G/A, G/G genotypes acute MI patients than that in A/A genotype acute MI patients. In conclusion, our study indicated that there was a significant association between the MCP-1 -2518G/A polymorphism and acute MI in the Egyptian population, but this significant association is dependent on the presence of MI risk factors.