Search Results (17)

Background/Objectives: Hepatitis A virus (HAV) yearly causes over 150 million new infections and around 40,000 deaths. Current vaccines are based on strains that grow poorly in cell culture, leading to high production costs and limited availability. This study aimed to compare the immunogenic properties of a novel HAV vaccine candidate based on the fast-growing HM175-HP strain with those of the parental slow-growing HM175-L0 strain, which derives from the cytopathic HM175 strain, like the prototype strain used in certain existing vaccines. Methods: The humoral and cellular immune response elicited by either HM175-HP or HM175-L0 vaccines was assessed in female BALB/c mice. Results: Both HM175-HP and HM175-L0 vaccines induced comparable levels of anti-HAV IgG, as well as similar numbers of antibody-secreting cells and cellular proliferation rates in immunized mice. Importantly, anti-HAV antibodies developed by HM175-HP-immunized mice were able to neutralize the HM175-L0 strain. In addition, both vaccines induced anti-HAV IgG1 antibodies, which are associated with Th2 immune response, but the HM175-HP vaccine showed a tendency to produce a greater IgG2a response, suggesting that it might elicit a higher Th1 response, which is of utmost importance for host defense against viruses. Conclusions: Our findings indicated that the fast-growing HM175-HP strain has similar immunogenic properties to the vaccine prototype-like HM175-L0, making it a promising candidate to reduce the elevated costs and time-consuming procedures of producing the current HAV vaccines. The novel HM175-HP-based vaccine would therefore facilitate mass vaccination programs and prevent vaccine shortages. Full article

Background: Torquetenovirus (TTV) viremia is increasingly recognized as a marker of immune competence. In the context of COVID-19, TTV viral load (VL) has been shown to predict anti-Spike antibody levels in severely immunocompromised patients. This study aimed to evaluate whether pre-vaccine TTV VL could predict humoral and cellular immune responses to SARS-CoV-2 mRNA vaccines in people living with HIV (PLWH) and healthy individuals (HP). Methods: TTV VL was measured via real-time PCR in serum samples collected before the second and third doses of mRNA vaccines in 93 PLWH and 48 HP (second dose) and 255 PLWH and 48 HP (third dose). Immune responses were assessed through anti-SARS-CoV-2 receptor-binding domain (RBD) IgG, neutralizing antibodies, and IFN-γ release. Statistical analyses included correlation studies between TTV VL and vaccine-induced immune responses. Results: TTV VL did not significantly correlate with anti-RBD IgG or neutralizing antibody levels in either cohort; highlighting its limited predictive value for humoral responses in relatively immunocompetent populations. However, a strong inverse correlation was observed between TTV VL and IFN-γ release after the third, but not the second, vaccine dose. These findings suggest that higher TTV VL, indicative of reduced immune competence, may impair T-cell-mediated immunity to vaccines. Conclusions: In virologically suppressed PLWH and HP, TTV VL is not a reliable predictor of humoral immune responses to COVID-19 vaccines. However, its inverse relationship with cellular responses warrants further investigation in more immunosuppressed populations. These results reinforce the continuum model of TTV VL as a biomarker, with predictive utility increasing alongside the degree of immunosuppression Full article

Background: Increased demand of the serological biomarker test (GastroPanel^®) in non-invasive diagnosis of gastric cancer (GC) risk conditions, i.e., atrophic gastritis (AG) and Helicobacter pylori (Hp) infection, prompted the design of GastroPanel^® Quick test (GPQT) (Biohit Oyj, Helsinki, Finland) for point-of-care (POC) settings. Objective: This study validated the diagnostic accuracy (DA) of GPQT in diagnosis of AG and Hp among gastroscopy referral patients. Methods: Altogether, 266 patients were enrolled among the consecutive gastroscopy referrals at the Department of Gastroenterology, Fortis Hospital (Punjab, India). All patients underwent gastroscopy with biopsies (n = 249) classified using the Updated Sydney System (USS) and finger prick blood sampling for GPQT testing. Results: Biopsy-confirmed AG was found in 15.3% (38/249) of the patients. The overall agreement between the GPQT and the USS classification was 71.4% (95% CI 65.4–77.0%), with the weighted kappa (κ_w) of 0.823 (95% CI 0.773–0.862). In ROC analysis for moderate/severe AG of the corpus (AGC) endpoint, AUC = 0.990 (95% CI 0.979–1.000) and AUC = 0.971 (95% CI 0.948–0.995) for PGI and PGI/PGII, respectively. Hp IgG Ab test detected biopsy-confirmed Hp with AUC = 0.836 (95% CI 0.783–0.889). Conclusions: The GPQT favourably competes in accuracy with the ELISA test version (unified-GP) in diagnosis of AG and Hp in patients referred for diagnostic gastroscopy. Full article

Helicobacter pylori (H.p.) is a Gram-negative bacterium endowed with gastric tropism. H.p. infection is widely spread throughout the world, accounting for various pathologies, such as peptic ulcer, gastric cancer, mucosa-associated lymphoid tissue lymphoma, and extra-gastric manifestations. This bacterium possesses several virulence factors, e.g., lipopolysaccharides (LPS), the toxins CagA and VacA, and adhesins, which elicit a robust immune response during the initial phase of the infection. Of note, the lipid A moiety of the LPS exhibits a lower endotoxic potency than that of other LPSs, thus facilitating infection through a mechanism of immune escape. H.p. colonization of the gastric mucosa induces an initial protective immune response with innate immune cells, e.g., neutrophils, monocytes, and macrophages, which engulf and kill bacteria. Moreover, the same cells, along with gastric epithelial cells, secrete cytokines and chemokines, which recruit T cells [T helper (h)1 and Th17 cells] to the site of infection, thus leading to H.p. eradication. In a large subset of individuals, the perturbation of such an immune equilibrium leads to a harmful response, with an expansion of T regulatory (TREG) cells, which suppress the protective immune response. In fact, TREG cells, via the production of interleukin (IL)-10, downregulate Th1- and Th17-related cytokines, thus allowing H.p. survival and the perpetuation of inflammation. As far as the humoral immune response is concerned, B cells, upon H.p. stimulation, produce autoreactive antibodies, and IgG anti-Le^x antibodies are harmful to the gastric mucosa. In this review, the structure and function of H.p. antigenic components and immune mechanisms elicited by this bacterium will be described in relation to gastric damage. Full article

Helicobacter pylori (H. pylori) has been implicated in colorectal carcinogenesis. Here, the association of immune responses to bacterial exposure with advancing stages of colorectal neoplasia was assessed by multiplex serology. Immunoglobulin (Ig) A and G antibody responses to thirteen proteins of H. pylori were measured by a Luminex-based multiplex assay in plasma from patients with colorectal cancer (CRC, n = 25), advanced adenoma (n = 82), or small polyps (n = 85) and controls (n = 100). Multivariable logistic regression was used to assess the association of bacterial seropositivity with colorectal neoplasia. The threshold for overall seropositivity required subjects to be positive for at least 4 out of the 13 tested antigens. In a cohort subset with matched data (n = 34), H. pylori seropositivity was correlated with bacterial abundance in both neoplastic and matched normal tissue. While no association was found between H. pylori seropositivity and the presence of CRC, IgA seropositivity to CagA was associated with a decreased risk of advanced adenoma (odds ratio, OR = 0.48, 95% confidence intervals, CIs: 0.24–0.96). Regarding IgG, higher antibody responses to HpaA was associated with advanced adenoma occurrence (OR = 2.46, 95% CI: 1.00–6.01), while responses to HP0395, CagA and Catalase were associated with polyp development (OR = 2.65, 95%, CI: 1.31–5.36, OR = 1.83, 95% CI: 1.01–3.32, and OR = 2.16, CI: 1.09–4.29, respectively). Positive correlations were found between H. pylori abundance in the normal mucosa and levels of both the IgA and IgG antibody response to Catalase and VacA antigens (r = 0.48, p < 0.01; r = 0.37, p = 0.04; r = 0.51, p < 0.01; and r = 0.71, p = 0.04, respectively). Conversely, H. pylori abundance was negatively correlated with levels of IgA antibody response to HpaA and with IgG antibody response to HP0231 in the diseased tissue (r = −0.34, p = 0.04 and r = −0.41, p = 0.01, respectively). The association between levels of H. pylori antigens and colorectal neoplasia risk gradually decreased with the adenoma progression, implicating the early activation of the immune response at the polyp stage. Thus, the evaluation of antibody response to certain bacterial antigens may indicate the presence of early-stage colorectal neoplasia. Further studies are needed to clarify the role H. pylori or the immune response to its antigens may have in colorectal carcinogenesis stages. Full article

Hypersensitivity pneumonitis (HP) represents the third common interstitial lung disease caused by an exaggerated immune response following the inhalation of organic and/or chemical environmental antigens. The aim of this study was to determine the cut-off values of specific IgG antibodies (named precipitins) and their association with clinical data in the diagnosis of HP. In this 10-year retrospective study, the IgG concentrations against six antigens, Penicillium chrysogenum/notatum, Aspergillus fumigatus, Alternaria alternata, Aspergillus niger, Micropolyspora faeni, and pigeon droppings, were retrieved. The controlled group was made of 1516 healthy subjects without diagnosis of lung pathologies, while the case group consisted of 54 individuals affected by HP. Considering all six IgG antibodies together and the 97.5% percentiles determined in the control group, 30 of 54 subjects (56%) had one or more positive precipitins. In these patients, the major frequencies found were IgG antibodies against pigeon droppings, followed by Penicillium chrysogenum/notatum and Aspergillus niger. Although the sensitivity of serum precipitins depends on the population enrolled and the method used, the cut-off values determined in this study can be a valuable tool for clinicians in the diagnosis of HP, in eliminating the antigens responsible from the environment, and in establishing more specific IgG panels. Full article

Hantavirus pulmonary syndrome (HPS) is a rodent-borne zoonotic disease that is endemic throughout the Americas. Agricultural activities increase exposure to wild rodents, especially for sugarcane cutters. We carried out a survey of the epidemiological aspects of HPS and investigated the prevalence of hantavirus infection in the sugarcane cutter population from different localities in the Brazilian Midwest region. We conducted a retrospective study of all confirmed HPS cases in the state of Goiás reported to the National HPS surveillance system between 2007 and 2017, along with a seroepidemiological study in a population of sugarcane cutters working in Goiás state in 2016, using the anti-hantavirus (Andes) ELISA IgG. A total of 634 serum samples from cane cutters were tested for hantavirus antibodies, with 44 (6.9%) being IgG-reactive according to ELISA. The destination of garbage was the only statistically significant variable (p = 0.03) related to the detection of hantavirus IgG (p < 0.05). We described the epidemiological profile of reported hantavirus cases in Goiás—a highly endemic area for HPS, and where the seroepidemiological study was conducted. Our results increase our knowledge about hantavirus infections in Brazil and highlight the vulnerability of sugarcane cutters to a highly lethal disease that, to date, has no specific treatment or vaccination. Full article

Inappropriate prescription of proton pump inhibitors (PPI) has been widely reported, often lacking initial exclusion of Helicobacter pylori (HP) infection and evaluation of gastric functional status. The aim of this study was to evaluate the utility of gastric functional tests to define the acid output, as well as HP status, in order to better direct PPI therapy prescription. Dyspeptic patients without alarm symptoms from a primary care population were evaluated. For each patient, serum Pepsinogen I (PGI) and II (PGII), gastrin 17 (G17) and anti-HP IgG antibodies (Biohit, Oyj, Finland) were determined. For each subject, data were collected regarding symptoms, past medical history of HP infection, and PPI use. Therapeutic response to PPIs was determined according to PGI and G17 values, where G17 > 7 in the presence of elevated PGI and absence of chronic atrophic gastritis (CAG) was considered an adequate response. Among 2583 dyspeptic patients, 1015/2583 (39.3%) were on PPI therapy for at least 3 months before serum sampling, and were therefore included in the study. Active HP infection and CAG were diagnosed in 206 (20.2%) and 37 (3.6%) patients, respectively. Overall, an adequate therapeutic response to PPIs was observed in 34.9%, reaching 66.7% at the highest dose. However, 41.1% and 20.4% of patients showed low (G17 1-7) or absent (G17 < 1) response to PPI, regardless of the dosage used. According to gastric functional response, most patients currently on PPI maintenance therapy lack a proper indication for continuing this medication, either because acid output is absent (as in CAG) or because gastrin levels fail to rise, indicating absence of gastric acid negative feedback. Lastly, HP eradication is warranted in all patients, and gastric function testing ensures this pathogen is sought for and adequately treated prior to initiating long-term PPI therapy. Full article

Phosphorylcholine (PC) is one of the main oxLDL epitopes playing a central role in atherosclerosis, due to its atherogenic and proinflammatory effects. PC can be cleared by natural IgM antibodies and low levels of these antibodies have been associated with human vein graft (VG) failure. Although PC antibodies are recognized for their anti-inflammatory properties, their effect on intraplaque angiogenesis (IPA) and intraplaque hemorrhage (IPH)—interdependent processes contributing to plaque rupture—are unknown. We hypothesized that new IgG phosphorylcholine antibodies (PC-mAb) could decrease vulnerable lesions in murine VGs.Therefore, hypercholesterolemic male ApoE3*Leiden mice received a (donor) caval vein interposition in the carotid artery and weekly IP injections of (5 mg/kg) PCmAb (n = 11) or vehicle (n = 12) until sacrifice at day 28. We found that PCmAb significantly decreased vein graft media (13%), intima lesion (25%), and increased lumen with 32% compared to controls. PCmAb increased collagen content (18%) and decreased macrophages presence (31%). PCmAb resulted in 23% decreased CD163+ macrophages content in vein grafts whereas CD163 expression was decreased in Hb:Hp macrophages. PCmAb significantly lowered neovessel density (34%), EC proliferation and migration with/out oxLDL stimulation. Moreover, PCmAb enhanced intraplaque angiogenic vessels maturation by increasing neovessel pericyte coverage in vivo (31%). Together, this resulted in a 62% decrease in IPH. PCmAb effectively inhibits murine atherosclerotic lesion formation in vein grafts by reducing IPA and IPH via decreased neovessel density and macrophages influx and increased neovessel maturation. PC-mAb therefore holds promise as a new therapeutic approach to prevent vein graft disease. Full article

Background: Molecular mimicry between Helicobacter pylori (Hp) and the host components resulting in induction of cross-reacting antibodies has been suggested as accessory mechanism in the development of coronary heart disease (CHD). A potential target for antibodies induced during Hp infection by the components of these bacteria might be amino acid sequence TVLLPVIFF (P1) of tumor necrosis factor receptor (TNFR), which is exposed on vascular endothelium and immunocompetent cells, driving inflammation. Aim: To examine whether anti-P1 IgG are induced during Hp infection in CHD patients. Methods: Sera from CHD patients infected with Hp (54) vs. sera of uninfected healthy donors (22) were tested by the ELISA for anti-H. pylori antibodies, anti-P1 IgG, and for antibodies towards control sequence IAKEGFEKIS (P2). Sera of Caviae porcellus infected experimentally with Hp (30) or uninfected (10) were included into this study. The same serum samples, which were positive for anti-P1 IgG, were adsorbed with Hp and then subjected to the ELISA. The biological activity of anti-P1 IgG was assessed in complement (C1q) binding assay. Results: Sera of 43 CHD patients seropositive for anti-Hp IgG contained anti-P1 IgG binding C1q. Additionally, 10 serum samples of animals seropositive for anti-Hp IgG contained anti-P1 IgG. Anti-P1 IgG in tested sera were neutralized by their adsorption with Hp. Conclusion: In CHD patients infected with Hp, antibodies cross-reacting with TNFR common sequence are produced. Further studies are necessary to define immunogenic Hp determinants and to confirm possible cellular effects of cross-reacting antibodies. Full article

Helicobacter pylori infections causing gastroduodenal disorders are a common medical problem. The aim of this study was to determine the specific motives of infrared spectroscopy (IR) spectra of sera from H. pylori-infected and uninfected children applied to investigate quantitatively-selected soluble biomarkers correlated with H. pylori infection in children and presumable consequent delayed growth. Sera from 41 children infected with H. pylori (Hp(+)) and 43 uninfected (Hp(−)) under the care of the Polish Mother’s Hospital in Lodz, Poland, were analyzed. The H. pylori status was confirmed by gastroscopy, ¹³C urea breath testing, and anti-H. pylori IgG antibodies. Infrared spectra were measured using an FTIR/FT-NIR Spectrum 400 spectrometer (PerkinElmer). The IR spectrum was measured in the wavenumber range 3000–750 cm⁻¹ and subjected to mathematical calculation of the first derivative. Based on the chi-square test, 10 wavenumbers of spectra correlating with H. pylori infection were selected for use in designing an artificial neural network. Ten parts of the IR spectra correlating with H. pylori infection were identified in the W2 and W3 windows associated mainly with proteins and the W4 window related to nucleic acids and hydrocarbons. Artificial neural networks for H. pylori infection were developed based on chemometric data. By mathematical modeling, children were classified towards H. pylori infection in conjunction with elevated levels of selected biomarkers in serum potentially related to growth retardation. The study concludes that IR spectroscopy and artificial neural networks may help to confirm H. pylori-driven growth disorders in children. Full article

Previously, we demonstrated that Heat Shock Protein 27 (HSP27) reduces the inflammatory stages of experimental atherogenesis, is released by macrophage (MΦ) exosomes and lowers cholesterol levels in atherosclerotic plaques. Recently, we discovered that natural autoantibodies directed against HSP27 enhance its signaling effects, as HSP27 immune complexes (IC) interact at the cell membrane to modulate signaling. We now seek to evaluate the potential role of the HSP27 IC on MΦ exosomal release and cholesterol export. First, in human blood samples, we show that healthy control subjects have 86% more exosomes compared to patients with coronary artery disease (p < 0.0001). Treating human THP-1 MΦ with rHSP27 plus a validated anti-HPS27 IgG antibody increased the abundance of exosomes in the culture media (+98%; p < 0.0001) as well as expression of Flotillin-2, a marker reflective of exosomal release. Exosome cholesterol efflux was independent of Apo-A1. THP-1 MΦ loaded with NBD-labeled cholesterol and treated with the HSP27 IC showed a 22% increase in extracellular vesicles labeled with NBD and a 95% increase in mean fluorescent intensity. In conclusion, exosomal abundance and secretion of cholesterol content increases in response to HSP27 IC treatment, which may represent an important therapeutic option for diseases characterized by cholesterol accumulation. Full article

Introduction: Helicobacter pylori infection is a well-established etiological factor for a variety of diseases such as peptic ulcer and gastric cancer. On the other hand, there is ongoing research suggesting that H. pylori might have a beneficial effect through a pivotal influence in the immunological response especially in asthma. The aim of the current case-control study was to evaluate the prevalence of H. pylori infection in asthmatic children. Methods: Twenty-seven children with exacerbation of persistent asthma, aged 8.6 ± 4.5 years (18 males, 9 females) and 54 age-sex-matched non-asthmatic controls were enrolled. Clinical examination and laboratory investigations were performed. Detection of H. pylori antigen (HpSA) in stool samples was performed by a commercial kit (bioNexia® kit, BioMérieux). Serum specific IgG antibodies were detected by a rapid chromatographic immunoassay (DIAsourceImmunoAssays). Serum IgE concentration was determined by electrochemiluminescence (ECL) (Roche Elecsys) and IgE levels ≥ 90 IU/mL were considered significantly elevated. Results: In 3 (11.1%) of the 27 asthmatic children H. pylori infection (based on both detection of HpSA and specific IgG-Abs) was established, whereas as many as 16 of the 54 (29.6%) non-asthmatic ones were found infected (odds ratio 0.1; 95%CI, 0.039–0.305, p = 0.026). Conclusions: Our findings reveal an inverse relationship between H. pylori infection and children's persistent asthma in Greece. Full article

Hemoglobin-based oxygen carriers (HBOCs) represent a propitious type of blood substitute to transport oxygen throughout the body while acting as a carrier in biomedical applications. However, HBOCs in blood are recognized and rapidly scavenged by the body’s innate immune systems. To overcome this problem, HBOCs require a surface modification that provides protection against detection and elimination in order to prolong their circulation time after administration. In this study, we investigated different surface modifications of hemoglobin submicron particles (HbMPs) by double/triple precipitation, as well as by adsorption of human serum albumin (HSA), hyaluronic acid (HA), and pluronic (Plu) to discover how diverse surface modifications influence the oxygen binding capacity and the binding of anti-hemoglobin (Hb) antibodies, immunoglobulin G (IgG), and haptoglobin (HP) to HbMPs. The particle size and zeta potential of the six types of HbMP modifications were analyzed by zeta sizer, confocal laser scanning microscopy, and transmission electron microscopy (TEM), and were compared to the unmodified HbMPs. The results revealed that all surface-modified HbMPs had a submicron size with a negative charge. A slight decrease in the oxygen binding capacity was noticed. The specific binding of anti-Hb antibodies, IgG, and HP to all surface-modified HbMPs was reduced. This indicates a coating design able to protect the particles from detection and elimination processes by the immune system, and should lead to a delayed clearance and the required and essential increase in half-life in circulation of these particles in order to fulfill their purpose. Our surface modification method reflects a promising strategy for submicron particle design, and can lead the way toward novel biomedical applications. Full article

Bird Fancier’s Lung (BFL) is a rare, nonatopic immunologic response to repeated or intense inhalation of avian (bird) proteins/antigens found in the feathers or droppings of many species of birds, which leads to an immune-mediated inflammatory reaction in the respiratory system. Although this is the most common type of hypersensitivity pneumonitis (HP) reported in adults, it is one of the classifications of a rare subtype of interstitial lung disease that occurs in the pediatric age group of which few case reports are available in the literature. The pathophysiology of HP is complex; numerous organic and inorganic antigens can cause immune dysregulation, leading to an immune-related antigen–antibody response (immunoglobulin G—IgG- against the offending antigen). Diagnosing BFL in the pediatric age group is challenging due to the history of exposure usually being missed by health care providers, symptoms and clinical findings in such cases being nonspecific and often misdiagnosed during the acute illness with other common diseases such asthma or acute viral lower respiratory tract infection, and the lack of standardization of criteria for diagnosing such a condition or sensitive radiological or laboratory tests. Treatment, on the other hand, is also controversial. Avoidance of the offending antigen could be the sole or most important part of treatment, particularly in acute mild and moderate cases. Untreated cases can result in irreversible lung fibrosis. In this case report, we highlight how children presenting with an acute viral lower respiratory tract infection can overlap with the acute/subacute phase of HP. Early intervention with pulse steroids markedly improves the patient’s clinical course. Full article