Clinical Association of a Soluble Triggering Receptor Expressed on Myeloid Cells-1 (sTREM-1) in Patients with Systemic Lupus Erythematosus.

A triggering receptor expressed on myeloid cells-1 (TREM-1) is a member of the immunoglobulin superfamily with an established role in innate and adaptive immune response. We aimed to determine the plasma concentrations and clinical association of sTREM-1 in Systemic Lupus Erythematosus (SLE) patients. Plasma from 79 SLE patients and 35 normal healthy subjects were assayed for sTREM-1 and IL-6 levels using Enzyme Linked Immunosorbant Assay (ELISA). The clinical disease characteristics and serological data were prospectively assessed. Disease activity was scored using the SLE disease activity index. We detected significantly higher levels of sTREM-1 in plasma of SLE patients than the healthy control group. We also detected high sTREM-1 levels in subgroups of patients with neuropsychiatric manifestations (NPLE) and patients with the total high disease activity and NPLE activity. In addition, sTREM-l levels were significantly correlated with parameters of disease activity, i.e. SLEDAI score, IL-6, hypoalbuminemia. On the other hand, we did not find significant differences in sTREM-1 levels in relation to age, disease duration, medications, ESR, other organ system involvement, or the presence of anti-dsDNA. Our preliminary data indicated that sTREM-1 levels may be an additional useful marker of disease activity in SLE. It also highlights its importance in patients with NPLE. An additional prospective longitudinal study should be carried out to support these findings.

Glutathione S transferase (GSTP 1, GSTM 1, and GSTT 1) gene polymorphisms in Egyptian patients with acute myeloid leukemia.

BACKGROUND: The super family of glutathione S-transferases (GSTs) is composed of multiple isoenzymes with significant evidence of functional polymorphic variation. GSTs detoxify potentially mutagenic and toxic DNA-reactive electrophiles, including metabolites of several chemotherapeutic agents, some of which are suspected human carcinogens. Polymorphisms within the phase II metabolizer enzymes GST T1, GST M1, and GST P1 affect the body's ability to detoxify a range of potential leukemogens encountered in the environment. AIM OF WORK: To address how differences in the human GST isoenzyme expression patterns influence cancer susceptibility, prognosis, and treatment. PATIENTS AND METHODS: A total of 50 patients with acute myeloid leukemia (AML), as well as 50 age and sex matched apparently healthy volunteers were genotyped for GSTP 1, GSTM 1, and GSTT 1 gene polymorphisms using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and conventional polymerase chain reaction (PCR), respectively. RESULTS: For GSTP1 313 A → G (GSTP1 Ile105Val) polymorphism, It was found that the wild genotype (AA) was significantly higher among control subjects (P value = 0.0277), while the frequency of heteromutant genotype (AG) and mutant G allele (AG + GG) was significantly higher among patients (P value = 0.0402, P value = 0.0277, respectively). For GSTM1 and GSTT1gene, we found statistically significantly higher frequency among patients regarding homozygous gene deletion (P value = 0.0005). CONCLUSION: We demonstrated that GSTM1 null or GSTT1 null genotypes may be considered independent risk factors for AML with no impact on prognosis and GSTP1 * 105 genotype is a prognostic factor, adding independent information to the routine laboratory parameters and cytogenetic and molecular alterations of the tumor cells.

Monoclonal gammopathy among patients with chronic hepatitis C virus infection.

BACKGROUND: An association between monoclonal gammopathies and chronic liver diseases has been previously reported. Hence, the objective of this study was to determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection in Egypt. METHODS: This is a prospective study of 200 HCV-positive and 100 HCV-negative patients with chronic liver diseases recruited consecutively at the Kasr El Aini Hospital Departments of Internal Medicine and Hematology, Cairo University. Clinical data were gathered, serum protein electrophoresis was performed and immunoelectrophoresis was carried out for the detection of monoclonal component. Histological examination of bone marrow was performed in patients with monoclonal gammopathy. RESULTS: A monoclonal band was detected in 2% of the HCV-positive patients and in 0% of the HCV-negative patients (P > 0.05). CONCLUSIONS: In this study, 4 cases of monoclonal gammopathy of undetermined significance were observed in the HCV-positive group, whereas none was observed in the HCV-negative group, which supports prior observations that HCV infection is associated with an excess risk for monoclonal gammopathy of undetermined significance.

Methylenetetrahydrofolate reductase gene polymorphisms (677C > T and 1298A > C) in Egyptian patients with non-Hodgkin lymphoma.

BACKGROUND: Folate metabolism plays an essential role in Deoxyribonucleic acid (DNA) synthesis and methylation processes. Deviations in the flux of the folate may affect the susceptibility to various cancers including lymphoma. AIM: The aim of this study was to investigate the genetic polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C/T and 1298A/C) and to evaluate its associations with the risk of Non Hodgkin lymphoma. MATERIALS AND METHODS: The study included 50 patients with diffuse large B cell lymphoma (DLBCL) as well as 50 age matched apparently healthy volunteers (as control). All the subjects included in the study were genotyped for the detection of the MTHFR gene polymorphisms (677C > T and 1298A > C) by using restriction fragment length polymorphism (PCR-RFLP). RESULTS: There were highly statistically significant differences between the 2 groups with respect to results of PCR-RFLP for MTHFR 677C→T polymorphism for CC genotype (P value = 0.001), statistically significant differences for CT (P value = 0.048) and TT (P value = 0.038) genotypes; however, no statistically significant differences regarding CC/CT or TT/CT alleles (P value = 0.052). Also, there were highly statistically significant differences between the patient and control groups with regards to the results of MTHFR1298 A/C polymorphism for the AA, AC genotypes as well as the AA/AC and CC/AC alleles (P value < 0.0001), and statistically significant difference regarding CC genotype (P value 0.0192). CONCLUSION: In conclusion, this study demonstrated a significant association between the MTHFR polymorphisms and the risk of DLBCL. Thus the study could support that folate intake together with the genetic basis may help in modifying the risk to lymphoma.

Role of soluble P-selectin and methylenetetrahydrofolate reductase gene polymorphisms (677C>T) in Egyptian patients with venous thromboembolism.

Venous thromboembolism (VTE) is a significant problem for surgical and medical hospitalized patients, leading to the possibility of serious illness and risk of death. The aim of the present study was to investigate soluble P-selectin levels and genetic polymorphisms in 5, 10-methylenetetrahydrofolate reductase (MTHFR 677C/T) and to evaluate its associations with VTE was the aim of work. The study involved 49 patients diagnosed as having VTE (as a patients group) as well as 24 apparently healthy volunteers (as controls group). All the participants included in the study were assessed for soluble serum P-selectin levels using the enzyme-linked immunosorbant assay technique. All the participants included in the study were genotyped for detection of MTHFR gene polymorphisms (677C > T) by restriction fragment length polymorphism. Concerning the results of soluble P-selectin, there were statistically significant differences between the two groups (P = 0.0210). Concerning the results of MTHFR gene polymorphisms, there were no statistically significant differences between the two groups regarding CT allele (P = 0.8790), but there were highly statistically significant differences between the two groups regarding CC, TT alleles as well as CC/CT and TT/CT alleles (P < 0.0001). According to our study, elevated soluble P-selectin levels as well as MTHFR gene polymorphisms are to be considered as independent risk factors for development of VTE, so it may be recommended to include P-selectin assay and detection of MTHFR gene polymorphisms when considering patients with thromboembolism even in the absence of any other predisposing factors.

Placental protein 13 as an early predictor in Egyptian patients with preeclampsia, correlation to risk, and association with outcome.

INTRODUCTION: Placental protein 13 (PP13) is a protein expressed only in the placenta. It is involved in gluing the placenta to the uterus and remodeling the maternal arteries to expand them. Women who subsequently develop preterm preeclampsia have low first trimester maternal serum. AIM OF WORK: The aim of this work was to assess the value of PP13 as an early marker for screening of preeclampsia and to correlate it with the PP13 messenger RNA (mRNA). PATIENTS AND METHODS: As a part of the Antenatal Screening Project, 100 women in the first trimester of pregnancy were selected and subdivided into 2 groups: 50 women who developed preeclampsia in their third trimester (patient group) and 50 women who completed normal uncomplicated pregnancy until full term (control group). Placental protein 13 level was measured using the commercially available enzyme-linked immunosorbent assay kit and PP13 mRNA was tested using reverse transcription polymerase chain reaction. RESULTS: The maternal serum PP13 level in the preeclamptic group was (157.9 ± 45.5 pg/mL), which is significantly lower than that of the control group (225.3 ± 67.3 pg/mL), with highly statistically significant difference (P < 0.0001). The frequency of maternal PP13 mRNA expression was lower in the preeclamptic group (28%) compared to that in the control group (76%), with highly statistically significant difference (P < 0.0001). CONCLUSION: Combined serum PP13 level assay and PP13 mRNA expression are reliable markers for early detection of preeclampsia, and we recommend doing it as a routine investigation during the first trimester.

Prevalence of occult hepatitis C virus in egyptian patients with chronic lymphoproliferative disorders.

Background. Occult hepatitis C virus infection (OCI) was identified as a new form of Hepatitis C virus (HCV), characterized by undetectable HCV antibodies and HCV RNA in serum, while HCV RNA is detectable in liver and peripheral blood cells only. Aim. The aim of this study was to investigate the occurrence of OCI in Egyptian patients with lymphoproliferative disorders (LPDs) and to compare its prevalence with that of HCV in those patients. Subjects and Methods. The current study included 100 subjects, 50 of them were newly diagnosed cases having different lymphoproliferative disorders (patients group), and 50 were apparently healthy volunteers (controls group). HCV antibodies were detected by ELISA, HCV RNA was detected in serum and peripheral blood mononuclear cells (PBMCs) by reverse transcription polymerase chain reaction(RT-PCR), and HCV genotype was detected by INNO-LiPA. Results. OCI was detected in 20% of patients group, compared to only 4% OCI in controls group. HCV was detected in 26% of patients group with a slightly higher prevalence. There was a male predominance in both HCV and OCI. All HCV positive patients were genotype 4. Conclusion. Our data revealed occurrence of occult HCV infection in Egyptian LPD patients at a prevalence of 20% compared to 26% of HCV.

Egyptian experience of reliability of 4T's score in diagnosis of heparin induced thrombocytopenia syndrome.

To evaluate the utility of the 4Ts clinical scoring system as a pretest probability method for detection of heparin-induced thrombocytopenia (HIT). Medical and surgical inpatients and outpatients at Kasr El Eini hospital. This single-centre series of 50 HIT testing referrals assessed combination of clinical score (thrombocytopenia, timing, thrombosis, other causes of thrombocytopenia not evident; 4T's), Heparin platelet factor 4 (H-PF4) rapid particle gel immunoassay (PaGIA) and 14C serotonin release assay (SRA) to develop a practical and well tolerated diagnostic strategy for HIT. Sixteen patients (32%) had a low 4T's score, 26 (52%) had an intermediate score and only eight (16%) had a high score. A positive H-PF4 by PaGIA was seen in seven patients (14%). As might be anticipated, the likelihood of obtaining a positive H-PF4 by PaGIA increased with an increasing clinical score, with positive H-PF4 by PaGIA results in low, intermediate and high scoring patients of 6.25, 7.7 and 50%, respectively. The positive predictive value of a positive PaGIA was 92%. The negative predictive value was 100%. Five patients (10%) in our cohort had a positive SRA. All patients with a positive SRA were included in the intermediate (two of 26 patients, 7.7%) or high (three of eight patients, 37.5%) score groups. The negative predictive value of a low 4T's score was 100%, effectively ruling out HIT. A low 4Ts score supports low probability of HIT based on the results of the PaGIA and SRA. Overall, the interrater reliability of the scoring system was fair.