Genetic profile variation in vaccine strains and clinical isolates of bordetella pertussis recovered from iranian patients

Background: Re-emergence of pertussis has been reported in Iran despite a high rate of vaccination coverage. Low efficacy of the vaccine might be due to the genetic divergence between clinical versus vaccine strains. In the current study, the genetic profiles of clinical isolates and vaccine strains of Bordetella pertussis (B. pertussis) were assessed by using Pulsed Field Gel Electrophoresis (PFGE). Methods: Following phenotypic and molecular identification of isolates, XbaIdigested genomic DNA of 5 clinical isolates, 2 vaccine strains and a Tohama I strain were analyzed by PFGE along with B. parapertussis as a control. Results: Seven distinct PFGE profiles were found among all examined isolates/ strains. In 5 clinical isolates, 4 profiles were identified whereas the vaccine strains displayed 2 distinct profiles. The reference strain, Tohama I had a distinct profile. Vaccine and clinical profiles had low similarity, with relatedness of approximately 40. Conclusion: The genetic profiles of B. pertussis were different between circulating isolates and vaccine strains used in the national vaccination programs. Since new genetic profiles of B. pertussis can be disseminated periodically, the profiles of isolates circulating in the population should be monitored over the course of the re-emergence. © 2014, Avicenna Journal of Medical Biotechnology. All rights reserved

Fc receptor-like 1-5 molecules are similarly expressed in progressive and indolent clinical subtypes of B-cell chronic lymphocytic leukemia

Fc receptor-like (FCRL) 1-5 molecules are exclusively expressed in B-cells and have recently been considered as potential targets for immunotherapy of B-cell malignancies. In this study, the expression pattern of FCRL1-5 molecules was investigated in Iranian patients with B-cell chronic lymphocytic leukemia (B-CLL). Our RT-PCR results have demonstrated that all FCRL molecules, except FCRL4, were expressed in the vast majority of the patients with B-CLL. However, comparison of the relative mRNA expression levels of FCRL between B-CLL (n = 86) and elderly normal subjects (n = 10) revealed significantly lower expression levels of FCRLl (p < 0.0001), FCRL3 (p = 0.01) and FCRL4 (p = 0.002), but not FCRL2 or FCRL5, in cases with B-CLL. No significant differences were observed between the indolent and progressive subtypes of patients with B-CLL. Comparison between the mutated and unmutated subtypes revealed a significantly higher expression level of FCRL3 (p = 0.017) in patients with mutated CLL. Surface and intracytoplasmic expression of FCRL1, 2, 4 and 5 in leukemic cells of 12 patients by flow cytometry revealed similar results to those obtained by RT-PCR with a few exceptions. Thus, while FCRL4 was expressed in only 2 samples at intracytoplasmic level, FCRL1 and 2 were expressed in the majority of samples, both at surface and intracytoplasm. FCRL5 protein was also detected in 10 samples, but surface expression was confirmed in only 2. Analysis of B-cells from 5 normal subjects by flow cytometry revealed higher expression levels of FCRL molecules compared to CLL. Our results indicate differential expression of FCRL molecules in B-CLL and suggest the potential implication of FCRL1 and 2 for immunotherapeutic interventions. © 2008 Wiley-Liss, Inc

Overexpression of orphan receptor tyrosine kinase Ror1 as a putative tumor-associated antigen in Iranian patients with acute lymphoblastic leukemia

Receptor tyrosine kinases (RTKs) are a group of enzymes involved in a variety of physiological and pathological processes. The human Ror1 is a member of the RTK family with unknown ligand and biological function. Overexpression of Ror1 has recently been reported in B-cell chronic lymphocytic leukemia. The aim of this study was to explore the expression profile of Ror1 in acute lymphoblastic leukemia (ALL) cells. Therefore, leukemic cells were isolated from the bone marrow and/or peripheral blood (PB) of 57 ALL patients. Immunophenotyping was performed by flow cytometry and mRNA expression was detected by RT-PCR. Overexpression of Ror1 mRNA was detected in 23 of 57 (40) ALL patients. A similar expression pattern was observed in ALL cell lines, with 4 of 12 (33) being positive. Stimulation of normal PB mononuclear cells with pokeweed mitogen and phorbol myristate acetate induced substantially higher Ror1 mRNA expression compared to unstimulated cultured cells. There has been neither a significant association between Ror1 expression and the immunophenotypic profile of the leukemic cells, nor with other clinical or hematological features of the patients. In conclusion, our findings propose Ror1 as a new tumor-associated antigen and a potential tool for targeted immunotherapy and monitoring of minimal residual disease in ALL. Copyright © 2008 S. Karger AG

Serum IL-17, IL-23, and TGF-β levels in type 1 and type 2 diabetic patients and age-matched healthy controls

Type 1 diabetes is recognized as an autoimmune inflammatory disease and low grade inflammation is also observed in type 2 diabetic patients. Interleukin 17 (IL-17) is a new player in inflammation. Th17 cells, as the main source of IL-17, require transforming growth factor β (TGF-β) and interleukin 23 (IL-23). The aim of this study was to investigate serum IL-17, IL-23 and TGF-β levels in diabetic patients and controls. In this case-control study, serum levels of IL-17, IL-23, and TGF-β were measured in 24 type 1 diabetic patients and 30 healthy controls using the ELISA method. Simultaneously, the same methodology was used to compare serum concentration of these three cytokines in 38 type 2 diabetic patients and 40 healthy controls. There was no significant difference between serum levels of IL-17 and IL-23 cytokines between cases and controls. However, TGF-β was significantly lower in type 1 diabetic patients (P<0.001). Serum IL-17 and IL-23 levels demonstrate no association with type 1 and type 2 diabetes, but, in line with previous studies, TGF-β levels were lower in type 1 diabetic patients. © 2014 Azam Roohi et al

Th1-Th17 ratio as a new insight in rheumatoid arthritis disease

The Th17, Th1 and dual Th17/Th1 cells are important players in rheumatoid arthritis (RA) disease. To assess their roles, the frequency and impact of these cells were investigated in patients with different disease activity. In 14 new cases and 41 established RA patients in comparison with 22 healthy controls, the percentages of Th17, Th1 and dual Th17/Th1 cells were determined by flow-cytometry and their correlations were investigated with disease activity score (DAS28). Moreover, serum levels of IL-6 and IL-17 as inducer and functional cytokines for Th17 were investigated. Finally, serum levels of anti citrullinated protein antibody (ACPA) and rheumatoid factor (RF) were assessed. Percentage of Th17 cells in RA patients were increased in comparison with healthy controls (p<0.01). In correlation with this finding, IL-17 and IL-6 cytokines in RA patients also increased (p<0.01). The Th1 cells in RA patients were less than healthy group (p<0.05) and showed negative correlation with disease activity (r=-0.328, p<0.01). Dual Th17/Th1 cell only in new cases of RA were more than healthy control groups (p<0.01). The Th1/Th17 ratio in RA patients is statistically different with healthy control group (p<0.01) and it has negative correlation with disease activity (r=-264, p<0.05). The levels of ACPA and RF were increased with disease progression. Decreasing of Th1/Th17 ratio in RA patient suggested a new paradigm in the field of autoimmune disease and indicated that imbalance or plasticity between these subsets can be important in progress, diagnosis and therapy of RA disease. © February 2018, Iran J Allergy Asthma Immunol. All rights reserved

Expression profile of galectin-1 and galectin-3 molecules in different subtypes of chronic lymphocytic leukemia

Galectin-1 (Gal-1) and galectin-3 (Gal-3) molecules are involved in many vital, biological, and pathological processes. In this study the expression pattern of these two molecules was investigated in leukemic cells from 85 Iranian chronic lymphocytic leukemia (CLL) patients, classified into indolent, progressive, mutated, and unmutated subtypes by semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) and flow cytometry methods. Our results showed significant downregulation of Gal-3, but not Gal-1, in CLL patients compared with normal subjects (p < .001). Higher representation of Gal-3 mRNA was observed in indolent patients compared with the progressive group (p < .05). Our findings imply a regulatory role for Gal-3 gene in initiation and/or progression of CLL. Copyright © 2010 Informa Healthcare USA, Inc

Expression profile of orphan receptor tyrosine kinase (ROR1) and Wilms' tumor gene 1 (WT1) in different subsets of B-cell acute lymphoblastic leukemia

Recent molecular investigations have demonstrated over-expression of a large number of tumor associated antigens (TAAs) in a variety of malignancies. Over-expression of ROR1 gene, a member of the receptor tyrosine kinase family, has recently been reported in B-cell chronic lymphocytic leukemia. Wilms' tumor gene 1 (WT1) has long been known as a universal TAA expressed in a variety of solid and hematopoietic malignancies. In the present study, the expression profile of ROR1 and WT1 was investigated in different immunophenotypic subsets of B-cell acute lymphoblastic leukemia (B-ALL) patients. RT-PCR method was used to determine the ROR1 and WT1 genes expression in bone marrow (BM) and peripheral blood (PB) samples from 51 newly diagnosed Iranian B-ALL patients. Isolated tumor cells from all patients were immunophenotyped by flow cytometry. Based on immunophenotypic results, our B-ALL patients were classified in four differentiation subsets; Pro-B (n = 7), Pre-B I (n = 29), Pre-B II (n = 13) and Immature/mature B-ALL (n = 2). Although ROR1 was over-expressed in more mature subsets (16.7, 42.9, 45.5 and 100, respectively), WT1 was more represented in immature subsets of B-ALL patients (57.1, 64.3, 38.5 and 0, respectively). Comparison of the frequency of ROR1 and WT1 positive samples at each immunophenotypic subtype revealed statistically significant difference only in Pre B I subtype (p = 0.02). Our results suggest that expression of ROR1 and WT1 in B-ALL is associated with the differentiation stage of the leukemic cells

Evaluation of Antibody Response to Polysaccharide Vaccine and Switched Memory B Cells in Pediatric Patients with Inflammatory Bowel Disease

Background/Aims: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. Methods: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. Results: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9±32.5 μg/mL vs 219.8±59.0 μg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. Conclusions: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods. (Gut Liver 2014;8:24-28)