Frequency analysis of HLA class I alleles in Iranian patients with progressive and non-progressive chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is a malignant disorder of B cell origin, with low incidence in Asian populations. In this study we investigated the HLA-class I A and B allele frequencies in 87 Iranian CLL patients and 64 healthy controls using sequence specific primer-polymerase chain reaction (SSP-PCR) technique. Our results showed increased frequencies of HLA-A11:01 (p=0.02) and HLA-B35:01 (p=0.002) alleles and HLA-A11:01/B35:01 haplotype (p=0.036) and decreased frequencies of HLA-A01:01 (p=0.02), HLA-A26:01 (p=0.03), HLA-B65:01 (p=0.03) and HLA-B53:01 (p<0.00001) alleles in CLL patients compared to the control group. Classification of the patients into non-progressive and progressive groups did not reveal significant differences for the frequency of any of the HLA-A and -B alleles or haplotypes between these two subtypes. Comparison between patients with immunoglobulin heavy chain variable region genes (IGHV) mutated (n=56) and unmutated (n=31) subtypes showed a significant increase in HLA-A32:01 (p=0.05) and HLA-A33:01 (p=0.05) alleles in IGHV unmutated patients compared to IGHV mutated patients. Similarly, a higher frequency of HLA-B52:01 (p=0.037) alleles was observed in CD38+ compared with CD38- patients. Our results obtained from an Iranian population indicate that CLL is associated with distinct HLA class I alleles and haplotypes some of which are linked to disease prognostic factors.Tehran University of Medical SciencesMinistry of Health and Medical Education of IranManuscrip

Immune Profiling of SARS-CoV-2; What We Know and What We Don’t Know

Coronavirus disease 2019 (COVID-19), described as World War 3, is the current worldwide health challenge and nearly all countries have so far faced this disaster. There is still no cure because of the complicated pathogenesis, however, there are several studies on track investigating different aspects of the immune response to the virus. In this review, we will provide an overview of recent investigations that have analyzed immune cells in patients with COVID-19. We will then discuss the differences in immune profiles between healthy controls and various clinical presentations, including asymptomatic, mild, moderate, and severe cases

Differential Responses of Anopheles stephensi (Diptera: Culicidae) to Skin Emanations of a Man, a Cow, and a Guinea Pig in the Olfactometer

Background: Biting habit of mosquitoes plays an important role in the epidemiology of mosquito-borne diseases. Mosquitoes use a set of elaborate sensory modalities to find their preferred hosts by exploiting cues emanating from a nearby host. It has been suggested that the chemical profile of skin can provide further support for anthropophilic mosquito species to find their suitable hosts. This study aimed at revealing the value of skin emanation for a zoophilic species like Anopheles stephensi as a model. Methods: Skin emanations of a man, a cow and a Guinea pig were collected by ethanol soaked cottons. Upwind responses of mosquitoes to 100 and 200 mu l of filtered skin materials were non-competitively explored in a dual-choice olfactometer. L-lactic acid and other chemical content of the skin samples were identified by an enzymatic kit and GC-MS, respectively. Results: Unexpectedly, only human skin emanation was resulted in the statistically significant activation and attraction responses of An. stephensi in the wind tunnel. L-lactic acid content of this skin sample was 10 and 29 times more than the cow and the Guinea pig, respectively. The possible role of lactic acid and a few other identified compounds have been discussed here. Conclusion: Anopheles stephensi showed higher and more specific upwind responses to human skin emanation in the olfactometer. Undoubtedly, the thorough explanation of this unexpected finding needs further investigation. But, if new data verify this result, then, it may be necessary to reconsider the role of skin emanation and thence the human blood index and vectorial capacity of this zoophilic mosquito

Immunophenotypic characterization of the leukemic B-cells from Iranian patients with chronic lymphocytic leukemia : association between CD38 expression and disease progression

Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have hetero-geneous clinical courses, thus several biological parameters need to be added to the cur-rent clinical staging systems to predict disease outcome. Recent immunophenotypic stud-ies performed mainly in Western populations have demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL. Objectives: To investigate the expression pat-tern of a variety of membrane antigens on leukemic cells from Iranian patients with CLL and to find out if there are any differences in the expression of these markers between in-dolent and progressive groups. Methods: In the present study, peripheral blood samples from 87 Iranian patients with B-CLL were analysed by flow cytometry. Results: In all cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast ma-jority of the cases expressed CD23, but failed to stain for CD3 or CD14. The leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87, 83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the indolent (n=42) and progressive (n=37) patients revealed significantly higher frequency and inten-sity of CD38 expression in progressive group (40.5%) compared to indolent (11.9%) pa-tients (p<0.05). None of the other membrane antigens were differentially expressed in these two groups of patients. Conclusion: Our results obtained in an Asian ethnic popula-tion confirm and extend previous findings obtained from Western populations regarding the association of CD38 expression and disease progression in B-CLL.Tehran University of Medical Sciences and the Ministry of Health and Medical Education of Iran.Publishe

Fabrication of an olfactometer for mosquito behavioural studies

Background & objectives: Olfaction is the major sensory modality involved in the resource searching behaviour of insects including vector mosquitoes (Diptera: Culicidae). To date, our current country-wide knowledge on the host-seeking behaviour of Iranian mosquitoes is mainly confined to host preference which has exclusively come from field studies. Olfactometer is a scientific tool by which more naive aspects of man-vector contact can be clarified under controlled and less biased conditions. Methods: The wind tunnel and stimulus delivery system was constructed from acrylic materials based on previously introduced models with some modifications. Air supply and required light were ensured by a powerful compressor and incandescent bulbs, respectively. Desired level of temperature was maintained by controllable heating radiators. For humidity production a unique in-built piezo system was devised in the course of the air flow. Fine regulators facilitated the continuous generatation of the humidity at a preset level. Results: Titanium tetrachloride smoke plus monitoring of the wind speed revealed that the flow of air was proper and invariable. A desired level of humidity and temperature could be set up in just 10 and 15-45 min, respectively. These physical parameters varied only +/-2% (humidity) and +/-0.15 degrees C (temperature) in a typical 20 min duration. Conclusion: The first sophisticated olfactometer in the field of medical entomology in Iran is reported here. Fast set up and stability of physical parameters are its salient features. It is expected that with the aid of this olfactometer further information on the physiological principles of the host-seeking behaviour of mosquitoes become available soon

Immunophenotypic characterization of the leukemic B-cells from Iranian patients with chronic lymphocytic leukemia

Background: Patients with B-cell chronic lymphocytic leukemia (B-CLL) have heterogeneous clinical courses, thus several biological parameters need to be added to the current clinical staging systems to predict disease outcome. Recent immunophenotypic studies performed mainly in Western populations have demonstrated the prognostic value of CD38 and ZAP-70 expression in B-CLL. Objectives: To investigate the expression pattern of a variety of membrane antigens on leukemic cells from Iranian patients with CLL and to find out if there are any differences in the expression of these markers between indolent and progressive groups. Methods: In the present study, peripheral blood samples from 87 Iranian patients with B-CLL were analysed by flow cytometry. Results: In all cases, the neoplastic cells displayed B-CLL phenotype (CD5+/CD19+/sIg+). The vast majority of the cases expressed CD23, but failed to stain for CD3 or CD14. The leukemic cells of most patients expressed CD27 (84/87, 95.4%) and CD45RO (74/87, 83.9%) molecules, suggesting a memory B-cell phenotype. Comparison between the indolent (n=42) and progressive (n=37) patients revealed significantly higher frequency and intensity of CD38 expression in progressive group (40.5%) compared to indolent (11.9%) patients (p<0.05). None of the other membrane antigens were differentially expressed in these two groups of patients. Conclusion: Our results obtained in an Asian ethnic population confirm and extend previous findings obtained from Western populations regarding the association of CD38 expression and disease progression in B-CLL.Tehran University of Medical sciences, Tehran, IranPublishe

Construction and characterization of a new chimeric antibody against HER2

Aim: Immunotherapy with anti-HER2 antibodies has shown promising results in patients with HER2-positive breast cancer. We have recently reported characterization of a mouse monoclonal antibody (mAb) against HER2, which binds to an epitope different from that recognized by trastuzumab and specifically inhibits proliferation of tumor cells overexpressing HER2. In the present study we report chimerization of this antibody. Materials & methods: The immunoglobulin variable region heavy and light chain genes of 1T0 hybridoma cells were amplified and ligated to human -1 and constant region genes using splice overlap extension PCR. The chimeric antibody was subsequently expressed and characterized by ELISA, western blot and flow cytometry. Results: The purified chimeric antibody specifically binds to recombinant HER2 and HER2-overexpressing tumor cells and inhibits proliferation of these cells. The binding affinity of the chimeric mAb was comparable with the parental mouse mAb. Conclusion: This chimeric anti-HER2 mAb is a potentially valuable tool for targeted immunotherapy.noneManuscrip

The influence of feeding linoleic, gamma-linolenic and docosahexaenoic acid rich oils on rat brain tumor fatty acids composition and fatty acid binding protein 7 mRNA expression

<p>Abstract</p> <p>Background</p> <p>Experimental studies indicate that gamma linolenic acid (GLA) and docosahexaenoic acid (DHA) may inhibit glioma cells growth but effects of oral consumption of these fatty acids on brain tumor fatty acid composition have not been determined in vivo.</p> <p>Methods</p> <p>GLA oil (GLAO; 72% GLA), DHA oil (DHAO; 73% DHA) were fed to adult wistar rats (1 mL/rat/day) starting one week prior to C6 glioma cells implantation and continued for two weeks after implantation. Control group were fed same amount of high linoleic acid safflower oil (74–77% linoleic acid). Fatty acid composition of tumor samples was determined in a set of 8–12 animals in each group and serum fatty acid in 6 animals per each group. Gene expression of tumor fatty acid binding protein 7 (FABP7), epidermal growth factor receptor (EGFR), peroxisome proliferator activated receptor γ (PPAR-γ) and retinoid × receptor-α (RXR-α) were determined in a set of 18 animals per group.</p> <p>Results</p> <p>DHAO feeding increased EPA of brain tumors and decreased ratio of n-6/n-3 fatty acids. Serum levels of EPA were also increased in DHAO group. A similar trend in serum and tumor levels of DHA were observed in DHAO group but it did not achieve statistical significance. GLAO increased serum concentration of GLA but had no significant effect on tumor GLA or dihomo-gamma linolenic acid (DGLA) concentrations. Gene expression of FABP7 was up-regulated in tumors of DHAO group but no other significant effects were observed on EGFR, PPAR-γ or RXR-α expression, and expression of these genes in tumors of GLAO were not different from SFO group.</p> <p>Conclusion</p> <p>Dietary supplementation of DHA containing oil could be an effective way to increase levels of long chain n-3 fatty acids in brain tumors and this increase may be mediated partly by up-regulation of FABP7 expression.</p

Comparative expression profile of orphan receptor tyrosine kinase ROR1 in Iranian patients with lymphoid and myeloid leukemias

It has recently been shown that ROR1, a member of the receptor tyrosine kinase family, is overexpressed in leukemic B cells of Chronic Lymphocytic Leukemia (CLL) and a subset of Acute Lymphoblastic Leukemia (ALL). In this comparative study the expression profile of ROR1 mRNA was investigated in Iranian patients with CLL and Acute Myelogenous Leukemia (AML) and the results were compared with those previously reported in our Iranian ALL patients. RT-PCR was performed on bone marrow and/or peripheral blood samples of 84 CLL and 12 AML patients. CLL samples were classified into immunoglobulin heavy chain variable region (IGHV) gene mutated (n = 55) and unmutated (n = 29) and also indolent (n = 42) and progressive (n = 39) subtypes. ROR1 expression was identified in 94% of our CLL patients, but none of the AML patients expressed ROR1. No significant differences were observed between different CLL subtypes for ROR1 expression. Taken together the present data and our previous results on ROR1 expression in ALL, our findings propose ROR1 as a tumor-associated antigen overexpressed in a large proportion of lymphoid (CLL and ALL), but not myeloid (AML) leukemias. Expression of ROR1 seems to be associated to lineage and differentiation stages of leukemic cells with a potential implication for immunotherapy.Tehran University of Medical SciencesPublishe

Comparative expression profile of orphan receptor tyrosine kinase ror1 in iranian patients with lymphoid and myeloid leukemias

It has recently been shown that ROR1, a member of the receptor tyrosine kinase family, is overexpressed in leukemic B cells of Chronic Lymphocytic Leukemia (CLL) and a subset of Acute Lymphoblastic Leukemia (ALL). In this comparative study the expression profile of ROR1 mRNA was investigated in Iranian patients with CLL and Acute Myelogenous Leukemia (AML) and the results were compared with those previously reported in our Iranian ALL patients. RT-PCR was performed on bone marrow and/or peripheral blood samples of 84 CLL and 12 AML patients. CLL samples were classified into immunoglobulin heavy chain variable region (IGHV) gene mutated (n=55) and unmutated (n=29) and also indolent (n=42) and progressive (n=39) subtypes. ROR1 expression was identified in 94% of our CLL patients, but none of the AML patients expressed ROR1. No significant differences were observed between different CLL subtypes for ROR1 expression. Taken together the present data and our previous results on ROR1 expression in ALL, our findings propose ROR1 as a tumor-associated antigen overexpressed in a large proportion of lymphoid (CLL and ALL), but not myeloid (AML) leukemias. Expression of ROR1 seems to be associated to lineage and differentiation stages of leukemic cells with a potential implication for immunotherapy.Tehran University of Medical Sciences and the Ministry of Health and Medical Education of Iran.Publishe