Occult hepatitis B virus (HBV) infection: a global challenge for medicine.

Hepatitis B virus (HBV) is a serious risk as a disease that can be spread through blood transfusion. Occult hepatitis B infection (OBI) is defined in a patient with the presence of HBV-DNA but a lack of HBsAg in the serum and hepatocytes. OBI can be considered as a high potential risk factor for inducing post transfusion hepatitis (PTH), hepatocellular carcinoma (HCC), cirrhosis, and reactivation of the HBV. Recently, several investigations from various regions of the world have reported PTH as well as HCC and cirrhosis among blood recipients with diseases such as thalassemia and other disorders requiring regular hemodialysis. This form of hepatitis also causes complications for individuals that are co-infected with other viruses such as HCV and HIV. Because of its extreme disease potential, OBI can be considered a high risk for PTH, HCC, and cirrhosis. Therefore, an understanding of the prevalence of OBI among blood donors is a critical strategy in most transfusion services. This review addresses the recent information regarding the prevalence of OBI worldwide, with an additional focus on Iranian blood donors.

Association of -592 region of IL-10 polymorphisms with asthma in south-eastern Iranian patients.

BACKGROUND: Cytokines are considered important factors for the pathogenesis of asthma as they play a key role in the regulation of immune responses. The aim of this study was to investigate the association between this disease and polymorphisms in the -592 region of the IL-10 gene. METHODS: This study was carried out on 100 asthmatic patients and 100 healthy controls. PCR-RFLP was applied to examine the polymorphisms in the -592 region of the IL-10 gene. RESULTS: Our results showed a significant difference between patients and controls in terms of genotypes and alleles of the -592 region of the IL-10 gene. CONCLUSIONS: According to our results, it can be concluded that the IL-10 promoter polymorphisms may play a crucial role in the pathogenesis of asthma.

T helper and B cell escape mutations within the HBc gene in patients with asymptomatic HBV infection: a study from the South-Eastern region of Iran.

BACKGROUND: Escape mutations potentially allow viruses to avoid detection and clearance by the host immune system and may represent a mechanism through which infections may persist in some patients. The association of the mutations in the HBcAg gene with Hepatitis B asymptomatic carriers (ASC) has not been studied adequately. The current study was aimed to investigate HBcAg18-27 CTL epitope mutations in ASC patients in the South-Eastern region of Iran. METHODS: 100 ASC patients were selected for this study and screened for HLA-A2 using flow cytometry. HBV-DNA was extracted from the HLA-A2 positive patients and the HBc gene was amplified using PCR. Direct double sequencing was performed to analyse mutations in the HBc gene of HBV isolates from patients with ASC. RESULTS: Overall, 25 (25%) of individuals were HLA-A2 positive. Direct double sequencing indicated no mutations in the HBcAg18-27 epitope. However, four mutations within the T helper and three mutations within the B cell epitopes of ASC patients were identified. CONCLUSIONS: The lack of mutations within the HBcAg18-27 epitope suggests that the antigenicity of this region is not altered in HBV isolates of our patients and therefore antigen presentation would occur normally to the patient's immune system through HLA-A2. However, in the course of this study we revealed some novel mutations within the T helper and B cell epitopes that may affect the efficiencies of immune response of ASC patients against these novel HBV epitopes.

Characterising frailty, metrics of continuous glucose monitoring, and mortality hazards in older adults with type 2 diabetes on insulin therapy (HARE): a prospective, observational cohort study.

BACKGROUND: To our knowledge, no previous study has examined the inter-relationship between frailty, dysglycaemia, and mortality in frail older adults with type 2 diabetes who are on insulin therapy. We used continuous glucose monitors (CGMs) to profile this patient population and determine the prognostic value of CGM metrics. We hypothesised that incremental frailty was associated with increased hypoglycaemia or time below range (TBR). METHODS: HARE was a multicentre, prospective, observational cohort study with mortality hazard analysis carried out in four hospitals in Hong Kong. Eligible participants were community-living adults aged 70 years and older; had had type 2 diabetes for 5 years or more; were on insulin therapy; were frail; and were not hospitalised at the time of frailty assessment and CGM recording. Glucose control was characterised according to the Advanced Technologies and Treatments for Diabetes 2019 international consensus clinical targets. Frailty index was computed, and comprehensive frailty assessments and targeted serum metabolic profiling were performed. The Jonckheere-Terpstra test for trend was used to analyse frailty index tertiles and variables. Inter-relationships between CGM metrics and frailty, glycated haemoglobin A1c (HbA1c), and serum albumin were characterised using adjusted regression models. Survival analysis and Cox proportional hazard modelling were performed. FINDINGS: Between July 25, 2018, and Sept 27, 2019, 225 participants were recruited, 222 of whom had CGMs fitted and 215 of whom had analysable CGM data (190 were frail, 25 were not frail). Incremental frailty was associated with older age, greater HbA1c, worse renal function, and history of stroke. Eight of 11 CGM metrics were significantly associated with frailty. Decreased time in range (TIR; glucose concentration 3·9-10·0 mmol/L) and increased time above range (TAR) metrics were strongly correlated with increased frailty and hyperglycaemia, whereas TBR metrics were marginally or not different between frailty levels. Glucose-lowering agents did not significantly affect regression estimates. In patients with HbA1c of 7·5% or more, reduced serum albumin was associated with level 2 TAR (glucose concentration >13·9 mmol/L) and dysglycaemia. During a median follow-up of 28·0 months (IQR 25·3-30·4), increased level 2 TAR was predictive of mortality explainable by frailty in the absence of detectable interaction. Each 1% increment of level 2 TAR was associated with 1·9% increase in mortality hazard. INTERPRETATION: In older adults with type 2 diabetes who are on insulin therapy, incremental frailty was associated with increased dysglycaemia and hyperglycaemia rather than hypoglycaemia. Mortality hazard was increased with severe hyperglycaemia. Future clinical studies and trials targeting actionable CGM metrics highlighted in this study could translate into improved care and outcomes. FUNDING: Health and Medical Research Fund, Food and Health Bureau, The Government of the Hong Kong Special Administrative Region of China.

Seminal levels of IL-10, IL-12, and IL-17 in men with asymptomatic chlamydia infection.

Chlamydia trachomatis, as an obligate intracellular parasite, usually causes asymptomatic genital tract infections in both men and women with several complications. The role of C. trachomatis infection in the secretion of a number of interleukins (ILs) from epithelial cells has been established by in vitro studies performed on various cell lines. The aim of this study was to detect the seminal levels of IL-10, IL-12, and IL-17 in men with asymptomatic chlamydia infection. Our case group study included 50 semen samples being PCR-positive for C. trachomatis from 585 semen samples and the ELISA method was applied for detection of IL-10, IL-12, and IL-17. Our results demonstrated that the semen levels of IL-10 and IL-17 were significantly increased, while IL-12 was decreased in C. trachomatis-infected patients. According to these results, it may be concluded that the increased and decreased semen levels of IL-10 and IL-12, respectively, lead to impaired immune responses against C. trachomatis. Increased semen levels of IL-17 may also be associated with the pathogenesis of C. trachomatis infection.

Effect of aqueous extract of Achillea millefolium on the development of experimental autoimmune encephalomyelitis in C57BL/6 mice.

OBJECTIVE: Achillea millefolium (A. millefolium) is widely used as an anti-inflammatory remedy in traditional and herbal medicine. In this study, we investigated the effect of an aqueous extract from A. millefolium on experimental autoimmune encephalomyelitis (EAE) and on the serum cytokine levels in C57BL/6 mice. MATERIALS AND METHODS: EAE was induced in 63 C57BL/6 mice weighing 20-25 g (8 weeks old). Following immunization, the treatment protocol was initiated by using different doses of an aqueous extract from A. millefolium (1, 5, and 10 mg/mouse/day). Histopathologic assessments were performed by hematoxylin and eosin (H and E) and luxol fast blue (LFB) staining. Behavioral disabilities were recorded by a camera. Serum levels of interleukin (IL)-10, IL-12, and transforming growth factor (TGF)-ß were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: On average, mice developed classical behavioral disabilities of EAE, 13.2 ± 1.9 days following immunization. Treatment of mice with A. millefolium led to delay the appearance of behavioral disabilities along with reduced severity of the behavioral disabilities. Treatment with A. millefolium prevented weight loss and increased serum levels of TGF-ß in immunized mice with MOG35-55. EAE-induced mice, which were treated with A. millefolium, had less cerebral infiltration of inflammatory cells. CONCLUSION: The results demonstrated that treatment with aqueous extract of A. millefolium may attenuate disease severity, inflammatory responses, and demyelinating lesions in EAE-induced mice. In addition, following treatment with A. millefolium, serum levels of TGF-ßwere increased in EAE-induced mice.

Interleukin-10 Serum Levels after Vaccination with In Vivo Prepared Toxoplasma gondii Excreted/Secreted Antigens.

OBJECTIVES: Toxoplasma gondii is a worldwide prevalent zoonotic parasite which causes toxoplasmosis. An appropriate vaccine for animals could interrupt the circle between animals and humans. Our previous study showed that excreted/secreted antigens (E/SA), derived from the peritoneum of mice infected with T. gondii tachyzoites could be considered as a good candidate for animal vaccination. Interleukin-10 (IL-10) inhibits proliferation of B and T lymphocytes and induces homeostasis in immune system responses. However, since IL-10 has also been shown to suppress the killing of T. gondii by human macrophages, the aim of this study was to evaluate IL-10 serum levels after vaccination with T. gondii E/SA prepared in vivo. METHODS: T. gondii tachyzoites were inoculated in the peritoneum of mice and harvested E/SA were used as a vaccine, with and without adjuvant, in T. gondii infected and un-infected mice. IL-10 serum levels were evaluated using the ELISA technique. RESULTS: The data showed that although serum levels of IL-10 were not changed at the early phases, they were elevated at the end phases of vaccination with T. gondii E/SA. CONCLUSION: Based on these and our previous results, it can be concluded that in vivo prepared T. gondii E/SA could be considered as a good candidate for animal vaccination.

Downregulation of CCR5 expression on the peripheral blood CD8+ T cells of southeastern Iranian patients with chronic hepatitis B infection.

Studies indicated that CC receptor 5 (CCR5), as a receptor for CC ligand 3, CCL4, and CCL5, plays important roles in the recruitment of T cytotoxic lymphocytes to the liver of chronic HBV (CHB)-infected patients. The main purpose of this study was to investigate the expression levels of CCR5 on the CD8(+) T lymphocytes of CHB patients. This clinical study was performed on 63 CHB patients and 96 healthy controls. Flow cytometric analysis was performed to examine the expression of CCR5 on CD8(+) T cells of CHB patients. Real-time PCR was also used for HBV-DNA quantification. The results of our study demonstrated that CCR5 expressing T cytotoxic cells were decreased significantly in CHB patients in comparison to healthy control. Based on our results, it can be concluded that the percent of CCR5(+)/CD8(+) T cells in Iranian CHB patients is significantly decreased, hence their migration to the infected liver, and HBV eradication from the hepatocytes is disrupted.

The IL-10 promoter polymorphism at position -592 is correlated with susceptibility to occult HBV infection.

Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which detectable amounts of HBV-DNA can be monitored in the peripheral blood of patients whereas the hepatitis B surface antigen is undetectable. The main aim of this study was to investigate whether there is a relationship between OBI and single nucleotide polymorphisms in the -592 region of the IL-10 gene. In this study, the polymorphism at position -592 of the IL-10 promoter of 57 OBI cases was compared and correlated to that of 100 healthy controls by PCR-RFLP techniques. Our results showed that patient and control groups had significant differences regarding genotypes and alleles of the -592 polymorphism in the IL-10 gene. Based on our results, it can be concluded that the -592 polymorphism within the promoter of the IL-10 gene is associated with OBI.

Interleukin (IL)-10 gene polymorphisms are associated with type 2 diabetes with and without nephropathy: a study of patients from the southeast region of Iran.

The impact of several environmental and genetic factors on diabetes and its complications is well documented. It has also been established that cytokines play a key role in the regulation of immune responses which have been shown to be important in the pathogenesis of diabetes. Studies showed that single-nucleotide polymorphisms within the -592 region of interleukin-10 (IL-10) are associated with the regulation of its expression. In this study, we aimed to find polymorphisms of this region that may be associated to type 2 diabetic (T2D) patients with and without nephropathy. In this study, peripheral blood samples were collected from 100 T2D patients without nephropathy, 100 T2D patients with nephropathy, and 100 healthy controls. DNA was extracted, and a polymerase chain reaction-restriction fragment length polymorphism technique was performed to examine the polymorphisms within the -592 region of the IL-10 gene. Our results showed a significant difference between the genotypes and alleles of the -592 region of IL-10 in nephropathic and non-nephropathic patients in comparison to the healthy controls. The differences between the two patient groups in relation to genotypes and alleles were not significant. Results of this study suggest that the functional gene polymorphism of IL-10 reported here may play an important role in the pathogenesis of diabetes, but it seems that these polymorphisms do not have an effect on the nephropathic complications of the disease.

The SDF-1 3'a genetic variation of the chemokine SDF-1α (CXCL12) in parallel with its increased circulating levels is associated with susceptibility to MS: a study on Iranian multiple sclerosis patients.

Immune system-related factors are important in pathogenesis of multiple sclerosis. The CXC chemokine SDF-1α (CXCL12) is involved in the immune responses. Hence, the aim of this study was to investigate the association between serum levels of SDF-1α (CXCL12) and its gene polymorphisms at position +801 with multiple sclerosis. In this experimental study, blood samples were collected from 100 multiple sclerosis patients and 100 healthy controls on EDTA pre-coated tubes. DNA was extracted and DNA samples were analyzed for SDF-1α (CXCL12) polymorphisms using PCR-RLFP in patients and controls. The serum levels of SDF-1α (CXCL12) were measured by ELISA. Demographic data were also collected by a questionnaire which was designed specifically for this study. Our results showed a significant difference between the A/A, A/G, and G/G genotype and A and G alleles of polymorphisms at position +801 of SDF-1α (CXCL12). Our results also showed that serum levels of SDF-1α (CXCL12) were markedly higher in patients than healthy controls, but no association was observed between SDF-1α (CXCL12) polymorphism and its serum levels. The results of this study might suggest the serum levels of SDF-1α (CXCL12) and its polymorphism play an important role in pathogenesis of multiple sclerosis. It is also worth noting that these factors could probably use as pivotal biological markers in the diagnosis of MS.

The status of humoral immunity in occult HBV infection in south-eastern Iranian patients.

BACKGROUND: Occult hepatitis B infection (OBI) is characterized as a form of hepatitis in which, despite of absence of detectable HBsAg, HBV-DNA is present in patient's peripheral blood. The aim of this study was to investigate components of humoral immunity during OBI as a possible measure of how patients respond to Hepatitis B viral infections. MATERIAL AND METHODS: In this study, HBsAg-/anti-HBc+/HBV-DNA+ samples were assigned as OBI cases and SRID techniques were performed to measure levels of circulating antibodies (IgG, IgM and IgA) as well as C3, C4. In addition, complement system function was assessed by CH50. RESULTS: Our results showed that the serum levels of IgG and C4 were significantly lower in OBI patients, while IgM and C3 were higher in patients when compared to healthy controls. Serum levels of IgA and CH50 were not significantly different between OBI patients and controls. DISCUSSION: Based on these results, it could be concluded that although OBI patients produced elevated levels of IgM there may be a problem converting and progressing this response to generate enough IgG to overcome HBV infection.