Serum level of fetuin-A in systemic lupus erythematosus patients: association with atherosclerosis and disease activity.

OBJECTIVES: We aimed in this study to determine the level of serum fetuin-A level in systemic lupus erythematosus patients, assess the correlation between serum fetuin-A level and the activity of disease and the frequency of musculoskeletal manifestations, and detect the frequency of atherosclerosis among these patients by using carotid ultrasonography. METHODS: This case-control study was carried out on 31 SLE patients attending the inpatient and outpatient clinics of Rheumatology and Rehabilitation Department, Faculty of Medicine, Zagazig university hospitals and 31 apparently healthy age- and sex-matched controls between January 1,2017, and December 31, 2018. RESULTS: There is a highly significant difference between the two studied groups as regard fetuin-A and carotid intima-media thickness. There is a strong positive significant correlation between fetuin-A with C3 and a negative significant correlation between fetuin-A with Anti-dsDNA, SLEDAI, and carotid intima-media thickness in case group. CONCLUSION: Fetuin-A levels were decreased in SLE patients, and these levels were inversely correlated with carotid intima-media thickness. Key Points • Fetuin-A level is a biomarker of atherosclerosis and asses disease activity in SLE patients.

Incidence of Philadelphia-chromosome in acute myelogenous leukemia and biphenotypic acute leukemia patients: And its role in their outcome.

BACKGROUND: Philadelphia-chromosome positive acute myeloid leukemia (Ph+ AML) is a rare entity and patient prognosis is poor, with short median survival. Biphenotypic acute leukemia (BAL) is a rare disorder that is difficult to diagnose and it displays features of both myeloid and lymphoid lineage. The aim of this study was to highlight the incidence of Philadelphia chromosome and its presence in cases of acute myeloid and biphenotypic leukemia and determine its role in the outcome of these leukemias. SUBJECTS AND METHODS: This study examined 464 subjects with newly diagnosed acute myeloid leukemia: 312 were males and 152 were females. All individuals were subjected to immunophenotyping and conventional karyotyping. FISH was used in failed cases of conventional cytogenetics analysis to quantify disease and to prove positive BCR-ABL fusion gene. RESULTS: the incidence of Ph+ chromosome was found to be higher in BAL (38.4%) than in AML (1.99%). There was statistically significant difference according to the age and the median survival time between the two groups. CONCLUSION: Detection of specific chimeric transcripts in AML and BAL at the time of diagnosis was crucial since it plays an important role for accurate risk stratification and treatment management.

CD40 ligand, Bcl-2 and apoptosis in B-chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is a haematopoetic neoplasm caused primarily by defects in apoptosis mechanisms and complicated by progressive marrow failure, immunosupression and increased resistance to chemotherapy. The CD40-CD40 ligand (CD40L) interaction has been shown to significantly increase antigen presentation in normal and malignant B-cells and it is a powerful regulator of cell survival. Bcl-2 expression is common in CLL and is associated with decreased overall survival. Our objective was to asses CD40 ligand (CD154) and Bcl-2 expressions and their correlation with clinical and laboratory features in CLL patients. This study was conducted on 40 subjects, including 10 healthy volunteers as the control group and 30 patients presented with de novo chronic lymphocytic leukemia (CLL), all of them were subjected to thorough history taking, full clinical examinations, routine laboratory investigations and flowcytometric assessment of CD40L and Bcl-2 on lymphocytes. There was a highly significant increase in TLC, absolute lymphocytic count, serum LDH, B2-microglobulin and Bcl-2 expression (P<0.001); there was a significant increase in CD40L expression (P<0.05); whereas there was a highly significant decrease in hemoglobin concentration and platelets count between the study group (P<0.001). There was no significant difference as regard direct Coombs' test between both groups. There was no significant relation between CD154 expression and clinical findings, Rai staging system and other laboratory parameters. CD40L expression is increased with staging of Modified Rai staging system but not reaching the significant level. There was no significant correlation between CD154 expression and some of clinical and laboratory parameters, whereas there was only significantly negative correlation between Bcl-2 expression and both haemoglobin concentration and platelets count (P<0.001). Combination of Bcl-2 antisense oligonucleotide with conventional chemotherapeutic drugs may enhance the cytotoxicity of these drugs and induces apoptosis.

Impact of CD4+CD25high regulatory T-cells and FoxP3 expression in the peripheral blood of patients with systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by various immunological abnormalities. Regulatory T cells (Tregs) CD4+CD25+ play an important role in maintaining tolerance to self-antigens controlling occurrence of autoimmune diseases. It has been shown that the transcription factor forkhead box P3 (FoxP3) is specifically expressed on CD4+CD25+T cells. FoxP3 has been described as the master control gene for the development and function of Tregs. A decrease in the number of CD4+CD25highFoxP3+ regulatory T cells can play a key role in the loss of tolerance to self antigens. The study was designed to assess expression levels of FoxP3 in peripheral CD4+CD25+ regulatory T cells in patients with SLE and to evaluate the level of some cytokines that are implicated in the extent of the disease activity. The study was carried out on 30 SLE patients, they were 27 females and 3 males, 10 age and sex matched healthy volunteers were studied as a control group. They were divided into two groups: group I: had active disease (12 patients) and group II: had inactive disease (18 patients) according to Systemic Lupus Erythematosus Disease Activity Index. All individual were subjected to CBC, ESR, s.creatinine, RF, CRP, C3, ANA, anti ds-DNA and flowcytometeric assay of CD4+CD25+ (Tregs) and FoxP3 for patients and controls. Quantitative determination of serum interleukin 10 (IL-10) and transforming growth factor-beta1 (TGF-beta1) concentrations in serum samples by ELISA technique. The results revealed a significant decrease of CD4+CD25high cells in peripheral blood in active lupus patients when compared with patients with inactive lupus and those in healthy controls. Intriguingly, the percentage level of FoxP3 on CD4+CD25high cells was significantly decreased in SLE patients with active disease (2.9 +/- 1.05) when compared with those with inactive SLE (3.5 +/- 0.8) and control groups (4.7 +/- 1.2) (P < 0.05). As regard cytokines levels; the level of IL-10 was significantly increased in patients with active and inactive disease (158.8 +/- 50.8, 82.8 +/- 14.08 respectively) when compared with the control group (P < 0.001). While, the level of TGF-beta1 was significantly decreased in patients with active and inactive disease (22.5 +/- 7.03, 29.07 +/- 10.14 respectively), when compared with the control group (P < 0.05). Our data revealed impaired production of Tregs in SLE patients, which may play a reciprocal role with some cytokines to affect the activity of the disease. Tregs cells should be the target to determine the clinical effectiveness of novel therapy to modulate Tregs in vivo besides the conventional treatments.