Cancer stem cell-targeted chimeric antigen receptor (CAR)-T cell therapy: Challenges and prospects

Cancer stem cells (CSCs) with their self-renewal ability are accepted as cells which initiate tumors. CSCs are regarded as interesting targets for novel anticancer therapeutic agents because of their association with tumor recurrence and resistance to conventional therapies, including radiotherapy and chemotherapy. Chimeric antigen receptor (CAR)-T cells are engineered T cells which express an artificial receptor specific for tumor associated antigens (TAAs) by which they accurately target and kill cancer cells. In recent years, CAR-T cell therapy has shown more efficiency in cancer treatment, particularly regarding blood cancers. The expression of specific markers such as TAAs on CSCs in varied cancer types makes them as potent tools for CAR-T cell therapy. Here we review the CSC markers that have been previously targeted with CAR-T cells, as well as the CSC markers that may be used as possible targets for CAR-T cell therapy in the future. Furthermore, we will detail the most important obstacles against CAR-T cell therapy and suggest solutions.

Imbalances in T cell-related transcription factors among patients with hashimoto's thyroiditis

Objectives: Imbalances in effector T cell functioning have been associated with a number of autoimmune diseases, including Hashimoto's thyroiditis [HT]. Differentiation of effector T helper [Th] 1, Th2, Th17 and regulatory T cell [Treg] lymphocytes is regulated by transcription factors, including Th1-specific T box [T-bet], GATA binding protein-3 [GATA3], retinoid-related orphan receptor [ROR]-alpha and forkhead box P3 [FOXP3]. This study aimed to investigate Th1/Th2, Th1/Treg, Th2/Treg and Th17/Treg balances at the level of these transcription factors

Methods: This study took place between October 2015 and August 2016. Peripheral blood mononuclear cells were collected from a control group of 40 healthy women recruited from the Zahedan University of Medical Sciences, Zahedan, Iran, and a patient group of 40 women with HT referred to the Hazrat Ali Asghar Hospital, Zahedan. Total ribonucleic acid extraction was performed and the gene expression of transcription factors was quantitated using a real-time polymerase chain reaction technique

Results: Expression of T-bet and GATA3 was significantly elevated, while FOXP3 expression was significantly diminished among HT patients in comparison with the controls [P = 0.03, 0.01 and 0.05, respectively]. Expression of RORalpha was higher among HT patients, although this difference was not significant [P = 0.15]. Expression of T-bet/FOXP3, GATA3/FOXP3 and RORalpha/FOXP3 ratios were increased among HT patients in comparison with the controls [P <0.02, <0.01 and <0.01, respectively]

Conclusion: These results indicate that HT patients have imbalances in Th1/Treg, Th2/Treg and Th17/Treg lymphocytes at the level of the transcription factors, deviating towards Th1, Th2 and Th17 cells. Correction of these imbalances may therefore be therapeutic

Increased concentrations of interleukin-33 in the serum and cerebrospinal fluid of patients with multiple sclerosis

Objectives: Interleukin [IL]-33 is a cytokine with both pro- and anti-inflammatory effects involved in the pathogenesis of some inflammatory diseases. The purpose of this investigation was to evaluate the serum and cerebrospinal fluid [CSF] IL-33 concentrations in patients with multiple sclerosis [MS]

Methods: Blood specimens were obtained from 140 patients with MS [46 males and 94 females] with various disease patterns and treatment plans and 140 healthy subjects [47 males and 93 females], who acted as a control group. CSF samples were collected from 20 MS group and 20 sex- and agematched patients with other neurological diseases of nonautoimmune etiology. The serum and CSF concentrations of IL-33 were measured by the enzyme-linked immunosorbent assay

Results: The serum and CSF IL-33 levels were significantly higher in the MS group compared to the control group [p<0.001 and p<0.050, respectively]. The serum IL-33 concentrations were also significantly higher in newly diagnosed [untreated] patients and patients treated with methylprednisolone or with interferon-beta and methylprednisolone compared to the healthy patient group [p<0.007, p<0.002, and p<0.010, respectively]. Moreover, the serum IL-33 concentrations in patients with relapsing-remitting [RRMS], primary progressive [PPMS], and secondary progressive [SPMS] forms of the disease were significantly higher than in the healthy control group [p<0.006, p<0.001, and p<0.020, respectively]

Conclusions: Our results showed increased concentrations of IL-33 in patients with MS including both untreated and treated MS patients and patients with the RRMS, SPMS, and PPMS forms. This suggests that IL-33 may be involved in the pathogenesis of all MS forms and treatment with methylprednisolone or both interferon-beta plus methylprednisolone has no influence on IL-33 concentrations

Ginger extract reduces the expression ofIL-17 and IL-23 in the seraand centralnervous system of EAEMice

Background: IL-17/IL-23 axis plays an important role in the pathogenesis of severalautoimmune diseases such as experimental autoimmune encephalomyelitis [EAE] andmultiple sclerosis [MS]. The immunomodulatory properties of ginger are reported in previous studies

Objective: To evaluate the effects of ginger extract on the expressionof IL-17 and IL-23 in a model of EAE

Methods: EAE was induced in C57BL/6 miceby immunization with myelin oligodendroglial glycoprotein and then treated with PBSor ginger extracts, from day +3 to +30. At day 31, mice were scarificed and theexpression of IL-17 and IL-23 mRNA in spinal cord were determined by using realtime-PCR. The serum levels of cytokines were measured by ELISA

Results: ThemRNA expression of IL-17, IL-23 P19 and IL-23 P40 in CNS and serum levels of IL-17 and IL-23 were significantly higher in PBS-treated EAE mice than non-EAE group[p<0.003, p<0.001, p<0.001, p<0.05 and p<0.01, respectively]. In 200 mg/kg gingertreatedEAE mice the mRNA expression of IL-17, P19 and P40 in CNS and serum IL-23 levels were significantly decreased as compared to PBS-treated EAE mice [p<0.05,p<0.001, p<0.001 and p<0.05, respectively]. Moreover, 300 mg/kg ginger-treated EAEgroup had significantly lower expression of IL-17, P19 and P40 in CNS and lowerserum IL-17 and IL-23 levels than PBS-treated EAE group [p<0.02, p<0.001, p<0.001,p<0.03 and p<0.004, respectively]

Conclusion: Ginger extract reduces the expressionof IL-17 and IL-23 in EAE mice. The therapeutic potential of ginger for treatment ofMS could be considered in further studies

Effects of garlic [Allium sativum] extract on the expression of receptor for advanced glycation end products and proinflammatory cytokines secretion in peripheral blood mononuclear cells from patients with type 2 diabetes mellitus

Background: receptor for advanced glycation end products [RAGE] plays a causative role in diabetes. Garlic [Allium sativum] belongs to compounds with anti-glycation activity that can be considered as probable therapeutic approaches in delaying or preventing the onset of diabetes complications. The aim of this study was to evaluate the influence of garlic on the RAGE expression and proinflammatory cytokines secretion in peripheral blood mononuclear cells [PBMCs] from patients with type 2 diabetes mellitus

Materials and Methods: the PBMCs were isolated from 20 patients with fasting blood sugar level above 126 mg/dl and treated with R10 fraction and whole garlic extract in presence or absence of glycated albumin. The expression of RAGE was detected using flow cytometry and the proinflammatory cytokines secretion was evaluated by ELISA

Results: glycated albumin increased RAGE expression and proinflammatory cytokines secretion. Treatment with whole garlic extract significantly reduced TNF-alpha and IL-1beta secretion and RAGE expression by PBMCs but R10 fraction augmented the proinflammatory cytokines and RAGE expression in absence or presence of glycated albumin

Conclusion: downregulation of RAGE expression was associated with decreased secretion of IL-1beta and TNF-alpha from PBMCs after treatment with whole garlic, while R10 fraction of garlic significantly augmented RAGE expression and proinflammatory cytokines secretion. These data indicates that modulation of RAGE expression may be one plausible reason for the garlic effects on proinflammatory cytokines secretion

Investigation of the association of ccl22 gene polymorphism rs4359426 with multiple sclerosis

Background: CCL22 is a chemokine that induces the migration of Th2- and regulatory T cells to the inflammatory sites. The aim of this study was to investigate the association of a single nucleotide polymorphism [SNP], rs4359426, in CCL22 gene, with multiple sclerosis [MS] in patients from southeast of Iran

Materials and Methods: the blood samples collected from 150 patients with MS and 150 healthy subjects as a control group. The serum levels of CCL20 measured by ELISA and the DNA analyzed for CCL22 polymorphism using PCR-RFLP method

Results: there were no significant differences in the frequencies of genotypes and alleles at SNP rs4359426 in CCL22 gene between MS patients and controls. No significant differences also observed between controls and patients with RRMS, SPMS, PPMS and PRMS patterns regarding the genetic variation of rs4359426. In both MS and control groups, no significant differences were observed between subjects with CC, CA and AA genotypes or between subjects with C and A alleles concerning rs4359426 with respect to the serum levels of CCL22

Conclusion: these results do not show any association between the investigated genotypes and alleles at rs4359426 in CCL22 gene with MS or its patterns in MS patients. The serum levels of chemokine did not also influence by genetic variation of SNP rs4359426

Lower circulating levels of chemokine CXCL10 in Helicobacter pylori- infected patients with peptic ulcer: influence of the bacterial virulence factor CagA

Alterations in CXCL10 [a Th1 chemokine] expression have been associated with various diseases. The aim of this study was to evaluate the serum CXCL10 levels in H. pylori- infected patients with peptic ulcer [PU], H. pylori- infected asymptomatic [AS] subjects and healthy H. pylori-negative subjects, and also to determine its association with bacterial virulence factor cytotoxin-associated gene A [CagA]. Serum samples from 90 H. pylori infected patients with PU [70 were anti-CagA[+], 20 were anti-CagA[-]], 65 AS carriers [40 were anti-CagA[+], 25 were anti-CagA[-]] and 30 healthy H. pylori-negative subjects [as a control Group] were tested for concentrations of CXCL 10 by using the ELISA method. The mean serum levels of CXCL10 in PU patients [96.64 +/- 20.85 pg/mL] were significantly lower than those observed in AS subjects [162.16 +/- 53.31 pg/mL, P < 0.01] and the control group [193.93 +/- 42.14 pg/mL, P < 0.02]. In the PU group, the serum levels of CXCL10 in anti-CagA[+] subjects was significantly higher in comparison to anti-CagA[-] patients [P < 0.04]. These results showed that the mean concentrations of CXCL10 in H. pylori-infected-PU patients was lower than AS carriers and control group. In the PU group, the serum levels of CXCL10 were associated with bacterial factor CagA

Higher serum levels of rheumatoid factor and anti-nuclear antibodies in helicobacter pylori-infected peptic ulcer patients

H. pylori infection has been associated with some autoimmune disorders. The aim of this study was to evaluate the serum concentrations of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected peptic ulcer patients, H. pylori-infected asymptomatic carriers and a healthy control group. A Total of 100 H. pylori-infected peptic ulcer patients, 65 asymptomatic carriers and 30 healthy H. pylori-negative subjects [as a control group] were enrolled into study. Serum samples of participants tested for the levels of rheumatoid factor and anti-nuclear antibodies by use of ELISA. The mean serum levels of rheumatoid factor and anti-nuclear antibodies in peptic ulcer group was significantly higher in comparison to the control group [p<0.05]. Although, the mean serum levels of rheumatoid factor and anti-nuclear antibodies in the asymptomatic carriers group was higher than those in the control group, the difference was not statistically significant. No significant differences were observed between peptic ulcer patients and asymptomatic carriers groups regarding the mean serum levels of rheumatoid factor and anti-nuclear antibodies. The mean serum levels of rheumatoid factor in men with peptic ulcer was significantly higher compared to the group of healthy men [p<0.05]. Although in female of peptic ulcer patients or asymptomatic carriers groups, the mean serum levels of rheumatoid factor was higher than that in healthy women, but the differences were not statistically significant. Also, no significant differences were observed between men and women with peptic ulcer, asymptomatic carriers control groups based on the serum levels of anti-nuclear antibodies. The results showed higher serum levels of rheumatoid factor and anti-nuclear antibodies in H. pylori-infected patients with peptic ulcer disease which represent the H. pylori-related immune disturbance in these patients. Additional follow-up studies are necessary to clarify the clinical significance of these autoantibodies in patients with H. pylori infection

Helicobacter pylori seropositivity in patients with type 2 diabetes mellitus in South-East of Iran

It has been also reported that that H. pylori infection may be responsible for some endocrine disorders, such as autoimmune thyroid diseases, diabetes mellitus and primary hyperparathyroidism. H. pylori which express cytotoxin-associated gene A [CagA] may be more virulent than those that do not. The aim was to evaluate the seroprevalence of anti-H. pylori IgG and anti-CagA antibodies in patients with type 2 diabetes mellitus [type 2 DM] and healthy individuals from Rafsanjan city [Iran]. A total of 100 patients with type 2 diabetes and 100 age-matched healthy individuals were enrolled to study. A blood sample was collected from each participant. The type 2 DM established according to the fasting blood glucose level of 126 mg/dl. The sera were tested for the presence of anti-H. pylori IgG antibodies and antibody to CagA by use of enzyme linked immunosorbent assay. The seroprevalence of anti-H. pylori antibodies in diabetic patients [76%] was similar to that observed in healthy subjects [75%]. The mean titer of anti-H. pylori IgG in healthy control group [131.63 +/- 11.68 U/ml] was significantly higher than diabetic group [54.43 +/- 4.50 U/ml; P<0.0001]. The prevalence of serum anti-CagA IgG antibodies was 78.9% in infected diabetic patients and 77.3% in healthy control group with mean titer of 75.02 +/- 4.54 U/ml and 84.34 +/- 5.85 U/ml, respectively. No significant differences were observed between diabetic and healthy control groups regarding the prevalence and the mean titer of anti-CagA IgG antibodies. In the diabetic group, the seropositive rate of anti-H. pylori IgG was higher in women as compared to men, but the difference was not statistically significant. These results show that H. pyloriseropositivity rate was similar in type 2 DM patients and non-diabetics control group. No association was also found between CagA-positive strains of H. pylori and type 2 DM

Non-association of IL-12 +1188 and IFN-gamma +874 polymorphisms with cytokines serum level in occult HBV infected patients

Occult hepatitis B infection [OBI] is identified as a form of hepatitis in which despite the absence of detectable HBsAg, HBV-DNA is observed in peripheral blood of patients. The main aim of this study has been to investigate the association between polymorphisms in +874 of IFN-gamma and +1188 of IL-12 with their serum level in patients suffering from OBI. In this experimental study, plasma samples of 3700 blood donors were tested for the presence of hepatitis B surface antigen [HBsAg] and anti-HBc by ELISA. The HBsAg[-]/anti-HBc[+] samples were selected and screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases and ARMS-PCR techniques were performed to examine the two known polymorphisms within IL-12 and IFN-gamma. In addition, the serum levels of IL-12 and IFN-gamma were also determined by ELISA. Results of this study demonstrated that, 352 [9.5%] out of 3700 blood samples were HBsAg[-]/anti-HBc[+]and HBV-DNA was detected in 57/352 [16.1%] of HBsAg[-]/anti-HBc[+] samples. Our results showed that groups showed significant difference in CC allele of +1188 region of IL-12 and no difference was observed in the other evaluated genes. Our results also showed that the alleles of +1188 region of IL-12 and alleles of +874 of IFN-gamma were also not associated with serum level of cytokines. According to the results of this study, it may be concluded that the polymorphisms in +1188 region of IL-12 and +874 region of IFN-gamma would not affect the expression of both cytokines at serum level in OBI patients

IL-10, TNF-alpha and IFN-gamma levels in serum and stomach mucosa of helicobacter pylori-infected patients

H. pylori is a human pathogen that colonizes the epithelium of the stomach. The host immune response may influence the disease process, where cytokines play important roles in the development of disease. In this study, the concentrations of selected cytokines in the gastric antrum and stomach body mucosa and also in the serum were evaluated. Eighty patients according to their rapid urease test were divided into two groups: H. pylori positive [n=39] and H.pylori-negative [n=41]. The concentrations of cytokines in biopsies and serum were determined by ELISA method. The mean TNF-alpha and IFN-gamma levels in the infected group were significantly higher than that of uninfected patients. In contrast, IL-10 level in most patients was undetectable. The mean antral of stomach TNF-alpha and IFN-gamma levels were significantly higher than that of the stomach body. IFN-gamma serum level showed positive correlation with antrum and stomach body levels, whereas no correlation was found in TNF-alpha in different samples. Higher levels of TNF-alpha and IFN-gamma in antral indicate that the colonization of bacteria in the antrum may be higher than stomach body [culture results from two sites support this statement]. Increased serum level of IFN-gamma indicates the activation of circulating-T cells against infection. Induced H. pylori-related TNF-alpha is concentrated is gastric mucosa and this pathogen does not cause any significant change in the serum level of this cytokine. Therefore H. pylori by inducing certain inflammatory cytokines but not IL-10 may contribute the process of disease development

High serum levels of rheumatoid factor and anti-phosphatidylserine antibody in patients with ischemic heart disease

Immunopathological and inflammatory processes play important roles in the initiation and development of Ischemic Heart Disease [IHD]. The aim of this study was to evaluate the serum levels of several autoantibodies including rheumatoid factor [RF], anti-nuclear antibodies [ANA], anti-small nuclear ribonucleoprotein [anti-Sm], anti-phosphatidylserine [anti-PS] and anti-cardiolipin [anti-CL] antibodies in patients with IHD. A total of 120 patients with IHD with acute myocardial infarction [AMI; n=60] or unstable angina [UA; n=60] and 60 sex- and age-matched healthy subjects were enrolled in this study. Serum samples of participants were tested for the ANA, anti-Sm, anti-PS and anti-CL antibodies by ELISA. Serum level of RF was measured by a turbidometric method. The mean serum levels of RF and anti-PS antibodies in AMI group and UA group were significantly higher than those observed in the control group [p<0.0001]. The mean serum levels of RF and anti-PS antibodies in AMI patients were significantly higher than the UA group [p<0.01 and p<0.001, respectively]. The mean serum levels of RF in men with AMI or UA diseases were significantly higher as compared to healthy control men [p<0.0001 and p<0.003, respectively]. The differences of the serum levels of ANA, anti-Sm and anti-CL antibodies were not significant between AMI, UA and the control groups. There was no difference in the serum levels of RF, ANA, anti-Sm, anti-PS or anti-CL antibodies in patients with traditional risk factors, including hypertension, dyslipidemia, diabetes and smoking, and those without a certain risk factor. Higher serum levels of RF and anti-PS antibody in patients with IHD may be considered as independent risk factors for IHD

Impact of opium on the serum levels of TGF-beta in diabetic, addicted and addicted-diabetic rats

Several cells of immune system such as regulatory T cells and macrophages secrete transforming growth factor-beta [TGF-beta] in response to different stimuli. This cytokine has inhibitory effect on immune system and diminished production of this cytokine is associated with autoimmune disorders. The aim of this study was to evaluate the influence of opium addiction on serum level of TGF-beta in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium addicted, diabetic and addicted-diabetic male and female rats. Serum level of TGF-beta was measured by ELISA. The results of our study indicated that the mean serum level of TGF-beta in female addicted rats was significantly increased compared to control group [p<0.004]. Conversely, in male addicted rats the mean serum level of TGF-beta was lower compared with control [p<0.065]. Our results suggest that opium and its derivatives have differential inductive effects on the cytokine expression in male and female rats

[Evaluation of expression rate of chemokines receptor CCR5 on peripheral blood CD8[+] T cells of occult hepatitis B infected patients]

Occult hepatitis B infection [OBI] is defined as a form of hepatitis B that despite absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. Genetic and immunological differences appear to play important roles in producing OBI. Therefore, this project was aimed to examine the expression of a chemokine receptor [CCR5] on CD8[+] T cells of OBI patients. In this experimental study, 3,700 HBsAg- plasma samples were collected. Samples were tested for anti-HBc antibody and all of HBsAg-/anti-HBc[+] samples were screened for HBV-DNA by PCR. HBV-DNA positive samples were assigned as OBI cases. Also, flow cytometry analysis was performed to examine the expression of CCR5 on CD8[+] T cells of OBI patients. Results of current study showed that 352 [9.5%] cases of samples were positive for anti-HBc. Examination of HBsAg/anti-HBc[+] samples for HBV-DNA by PCR showed that 57 [16.1%] cases had HBV-DNA. Flow cytometric studies indicated lymphocytosis in these patients; however, the number of cells which expressed CD8[+] and CCR5 is decreased significantly in patients, compared to healthy control. In addition to CD8[+] T cells, the expression of CCR5 is also decreased on all immune cells. One of the chemokine receptors which are expressed by CD8[+] T cells is CCR5 and these cells are recruited to infected tissues, including liver by CCR5. Therefore, based on results of this investigation, one may conclude that due to the decreased expression of CCR5, the CD8[+] T cells are unable to respond to the chemokines [CCR5 ligands] and, hence, can not immigrate to the infected liver and incorporate in clearance of hepatitis B virus

Expression of stromal derived factor alpha [SDF-1a] by primary hepatocytes following isolation and heat shock stimulation

Stromal derived factor-alpha [SDF-1-alpha] is a CXC chemokine which has been demonstrated as a recruitment factor for leukocytes to the site of inflammation, infection, injury and following stress. This chemokine has been shown to be expressed by liver cells and in liver diseases. Hence, the aim of this study was to examine the expression of SDF-1 by hepatocytes in responses to the stress imposed during isolation by collagenase perfusion and under heat shock stimulation. In this study hepatocytes [2-5 x 10[6]] were isolated from male Sprague Dawley rat liver and cultured in plates that were pre-coated with collagen Type-I matrix. The western and northern blotting analysis were employed to detect SDF-1 at protein and mRNA levels in isolated and cultured hepatocytes in response to isolation and heat shock stresses. The SDF-1 is expressed by isolated rat hepatocytes immediately after isolation and early culture and decreased with time. SDF-1 protein was highly expressed in freshly isolated cells and decreased by time [27h] [P < 0.05]. mRNA was also expressed in freshly isolated cells [0h] but decreased after 24h of culture [P < 0.01]. This results also demonstrated that expression of SDF-1 by hepatocytes was increased in response to heat shock at different time points comparing with control [P < 0.01]. These results demonstrated that the isolation and heat shock stresses induced the expression of SDF-1 in hepatocytes in a time-dependent manner. Accordingly, it seems that hepatocytes mimic the experiences that liver experience after injury in vivo and therefore, produce stress related agents like chemokines to overcome such a injurious condition

High sensitivity C-reactive protein and immunoglobulin G against chlamydia pneumoniae and chlamydial heart shock protein-60 in ischemic heart disease

Inflammation and infectious agents such as Chlamydia pneumoniae have been associated with cardiovascular disease. To evaluate the serum high sensitivity C - reactive protein [hs-CRP] and antibodies against Chlamydia pneumoniae and Chlamydial heat shock protein-60 [Cp-HSP60] in patients with ischemic heart disease [IHD]. 62 patients with IHD having either acute myocardial infarction [AMI; n=31] or unstable angina [UA; n=31] and 31 sex- and age- matched healthy subjects as a control group were enrolled in this study. Serum samples of participants were tested for the presence of hs-CRP and antibodies against C. pneumoniae and Cp-HSP60 using ELISA method. The seroprevalence of anti-C. pneumoniae antibody in AMI group [93.5%] or UA group [90.3%] was significantly higher than the control group [61.3%; p<0.001]. The seroprevalence of anti-Cp-HSP60 IgG was 22.6% in healthy subjects with mean end titer of 43.1 +/- 6.32. The seropositive rates of anti-Cp-HSP60 were 48.4%, 54.8% and 51.6% in AMI, UA and the overall IHD groups with mean end titers of 94 +/- 22.86, 113.8 +/- 24.25 and 103.9 +/- 16.57, respectively. Both the seroprevalence and the mean titer of anti-Cp-HSP60 in patients groups were significantly higher than those observed in the control group [p<0.04 and p<0.03, respectively]. Moreover, the mean serum hs-CRP levels was significantly higher in the IHD group as compared to the control group [21.6 Mu g/ml +/- 3.73 vs 2.5 Mu g/ml +/- 0.52; p<0.00001]. The mean serum hs-CRP levels of AMI [30.3 Mu g/ml +/- 6.07] or UA [12.9 Mu g/ml +/- 3.85] groups were also significantly higher than those observed in the control group [p<0.00001 and p<0.001, respectively]. Furthermore, the difference of the mean serum hs-CRP levels between AMI and UA groups was also significant [p<0.02]. These results showed that the seroprevalence of antibodies against C. pneumoniae and Cp-HSP60 and the serum levels of hs-CRP and anti-Cp-HSP60 IgG were higher in patients with IHD

[Occult HBV infection in Rafsanjanese blood donors]

Occult hepatitis B infection is a form of hepatitis in which despite of absence of detectable HBsAg, HBV-DNA is present in peripheral blood of patients. This clinical form of B hepatitis creates some problems for the Iranian blood transfusion services. Therefore, the aim of this study was the evaluation of status of occult hepatitis B infection in the Rafsanjanese blood donors. In this cross-sectional study, total of 3700 blood donor samples were collected and tested for HBsAg and anti-HBs using ELISA. The HBsAg negative and anti-HBc positive samples were selected and screened for HBV-DNA using PCR. Results of current study indicated that 352 [9.5%] of 3700 blood samples were HBsAg- and anti-HBc+. HBV-DNA was detected in 57 [16.1% of HBsAg- and anti-HBc+ and 1.54% of total samples] samples. Results of this study are in agreement with our previous studies in the prevalence of OBI. Therefore, it seems that occult hepatitis B infection rate is high in the Iranian blood donors and probably is one of the main causes of post-transfusion hepatitis

[Evaluation of some immune system components in hyperthyroid women]

The immune system and the endocrine system are, respectively, to defend the body against infections and to regulate physiologic activities of the body.Experimental as well as clinical evidence support the close interaction and bi-directional communication between the endocrine and immune systems. Some disorders in immune system were observed in experimental thyroid abnormalities. The aim of this study is to evaluate some immunological factors in hyperthyroid females. In this descriptive study, blood samples were collected from 50 females with hyperthyroid disease and a control group consisting of 50 sex - and age - matched euthyroid subjects. Thyroid function was assesed according to measurent of T3, T4 and TSH levels. The following parameters were studied in both groups: total and differential white blood cell counts [determined on stained-blood smear], serum concentration of immunoglobulins including: IgG, IgA, IgM [measured by SRID method] and IgE [quantitated by ELISA technique], seropositivity rates of CRP [determined by latex agglutination method], C3 and C4 complement components measured by SRID method. The mean serum concentrations of IgG, IgA, IgM and IgE were 2312.4 +/- 584 mg/dl, 296 +/- 87 mg/dl, 118.8 +/- 28 mg/dl and 301 +/- 264 IU/ml in hyperthyroid females and were 1539 +/- 974 mg/dl, 243 +/- 116 mg/dl, 140.1 +/- 68.9 mg/dl and 109.8 +/- 115 IU/ml in euthyroid subjects, respectively. Statistical analyses showed that the mean serum levels of IgG, IgA and IgE were significantly higher in hyperthyroid group as compared to euthyroid group. The seropositive rate of CRP was 20% and 4% in hyperthyroid and euthyroid groups, respectively. The seropositive rate of CRP was also significantly higher in hyperthyroid group as compared to euthyroid group. However, IgM, C3 and C4 levels and white blood cell counts were similarly expressed in two groups. The results indicate that some immunological alterations such as elevation of serum IgG, IgA and IgE levels and higher seropositive rate of CRP occur in hyperthyroid women

Expression of IP-10 chemokine is regulated by pro-inflammatory cytokines in cultured hepatocytes

Chemokines are classified in four distinct groups as CXC, CC, CX3C and C, depending on the presence or absence of a motif called ELR [Arg-Leu-Glu] before the first cysteine residue in their structure. CXC chemokines are also subdivided into ELR+and ELR-. Increasing evidence has indicated the existence of a chemokine network in the liver which is involved in both physiological responses and, under certain circumstances, pathological and repair processes following hepatic injury. The CXC chemokines play a major role in both these processes, and much attention has been focused on their therapeutic applications to liver disease. The aim of this study was to examine the response of cultured hepatocytes to exogenous inflammatory cytokines [TNF-alpha and IFN-gamma] regarding expression of IP-10 and growth regulatory oncogen [Gro] chemokines. In this study we employed western and northern analysis to measure chemokines at the level of protein and mRNA by hepatocytes in response to pro-inflammatory cytokines. We found that, the pro-inflammatory cytokines, TNF-alpha and IFN-gamma, selectively stimulated expression of IP-10 but were without effect on Gro. This confirms a potential direct involvement of these cytokines in chemokine production by hepatocytes. Thus, IFN-gamma and TNF-alpha may play a role in hepatic injury and inflammation and produce some of their biological effects by localized induction of chemokines by hepatocytes. Given the similarity to an acute phase response, we were able to show that IFN-gamma and TNF-alpha mimicked the effects of cell isolation and culture on induction of IP-10 expression. Further, evidence for linkages between IFN-gamma and TNF-alpha and liver injuries is seen in hepatitis C and hepatitis B in which increased levels of TNF-alpha and its soluble receptor were reported

Evaluation of Serum Interleukin-18 levels in Helicobacter Pylori-infected peptic ulcer patients and its Association with Bacterial CagA Virulence Factor

Helicobacter pylori infection is one of the most common gastrointestinal infections worldwide. Predominant T-helper 1 [Th1] responses with increased gamma interferon [IFN- gamma] levels have been proposed to play an important role in H. pylori-induced peptic ulcer. However, bacterial factors contributing to the initiation of Th1 polarization of H. pylori-specific immune responses have not been characterized. Comparing serum concentrations of IL-18 in H. pylori-infected peptic ulcer [PU] patients, H. pylori-infected asymptomatic [AS] carriers and healthy control group and its association with bacterial virulence factor CagA. Thirty H. pylori-infected PU patients [20 patients were positive for anti-CagA antibody and 10 patients were negative for anti-CagA antibody], 30 H. pylori-infected [AS] carriers [15 subjects with positive test for anti-CagA antibody and 15 subjects with negative test for anti-CagA antibody] and 20 healthy uninfected subjects were included in this study. Serum concentration of IL-18 was measured by ELISA method. The mean serum levels of IL-18 in PU patients [333.2 pg/ml +/- 158], was significantly higher than those found in AS [146.5 pg/ml +/- 90.1; P<0.001] and healthy control [82.2 pg/ml +/- 45.7; P<0.0001]. In both PU and AS groups, mean serum IL-18 levels in subjects with positive test for anti-CagA antibody were significantly higher than those observed in subjects with negative test for anti-CagA antibody. No significant difference was observed between serum IL-18 levels of healthy uninfected control and AS carriers with negative test for anti-CagA antibody. The results of the present study showed higher serum concentrations of IL-18 in peptic ulcer patients compared with H.Pylori carriers and healthy controls. This difference in cytokine levels may be explained by differential expression of H.Pylori CagA gene during the course of the infection