Immune Response In Individuals Research Articles

Prevalence of specific immunoglobulin E and G against Aspergillus fumigatus in patients with asthma.

Background and Purpose: Aspergillus fumigatus as a ubiquitous fungus can be found in the respiratory tract of the asthmatic and healthy people. The inhalation of Aspergillus spores leads to an immune response in individuals with asthma and results in the aggravation of the clinical symptoms. The present study aimed to investigate the prevalence of specific immunoglobulin E and G (IgE and IgG) against A.fumigatus in asthmatic patients.Materials and Methods:This study was conducted on 200 consecutive patients with moderate to severe asthma referring to Masih Daneshvari hospital Tehran, Iran, from January 2016 to February 2018. Skin prick test (SPT) was performed in all subjects with Aspergillus allergens. Moreover, all patients underwent specific IgE testing for Aspergillus using Hycor method. Enzyme immune assay was applied to measure total IgE and Aspergillus-specific IgG.Results:According to the results, the mean age of the patients was 45.8 years (age range: 18-78 years). The mean levels of total IgE and Aspergillus specific IgE in asthmatic patients were obtained as 316.3 (range: 6-1300 IU/ml) and 1.5 (range: 0.1-61.3 IU/ml), respectively. Out of 200 patients, 27 (13.5%), 65 (32.5%), 22 (11.0%), and 86 (43.0%) cases had positive Aspergillus SPT, total IgE of > 417 IU/ml, Aspergillus-specific IgE, and IgG, respectively. The level of these variables in patients with severe asthma were 16 (16.5%), 36 (37.1%), 15 (15.5%), and 46 (47.4%), respectively.Conclusion:As the findings indicated, reactivity to Aspergillus is a remarkable phenomenon in asthmatic patients. It is also emphasised that the climatic condition may affect the positive rate of hypersensitivity to Aspergillus.

A modified anthrax toxin-based enzyme-linked immunospot assay reveals robust T cell responses in symptomatic and asymptomatic Ebola virus exposed individuals.

BackgroundEbola virus (EBOV) caused more than 11,000 deaths during the 2013–2016 epidemic in West Africa without approved vaccines or immunotherapeutics. Despite its high lethality in some individuals, EBOV infection can produce little to no symptoms in others. A better understanding of the immune responses in individuals who experienced minimally symptomatic and asymptomatic infection could aid the development of more effective vaccines and antivirals against EBOV and related filoviruses.Methodology/Principle findingsBetween August and November 2017, blood samples were collected from 19 study participants in Lagos, Nigeria, including 3 Ebola virus disease (EVD) survivors, 10 individuals with documented close contact with symptomatic EVD patients, and 6 control healthcare workers for a cross-sectional serosurvey and T cell analysis. The Lagos samples, as well as archived serum collected from healthy individuals living in surrounding areas of the 1976 Democratic Republic of Congo (DRC) epidemic, were tested for EBOV IgG using commercial enzyme-linked immunosorbent assays (ELISAs) and Western blots. We detected antibodies in 3 out of 3 Lagos survivors and identified 2 seropositive individuals not known to have ever been infected. Of the DRC samples tested, we detected antibodies in 9 out of 71 (12.7%). To characterize the T cell responses in the Lagos samples, we developed an anthrax toxin-based enzyme-linked immunospot (ELISPOT) assay. The seropositive asymptomatic individuals had T cell responses against EBOV nucleoprotein, matrix protein, and glycoprotein 1 that were stronger in magnitude compared to the survivors.Conclusion/SignificanceOur data provide further evidence of EBOV exposure in individuals without EVD-like illness and, for the first time, demonstrate that these individuals have T cell responses that are stronger in magnitude compared to severe cases. These findings suggest that T cell immunity may protect against severe EVD, which has important implications for vaccine development.

Waterborne Cd2+ weakens the immune responses of blood clam through impacting Ca2+ signaling and Ca2+ related apoptosis pathways

Exposure to heavy metals such as Cadmium (Cd) may exert detrimental impacts on the immune responses of marine bivalve species. However, the immunotoxicity of Cd on blood clams remains unknown to date. Furthermore, though Cd2+ is known to compete with calcium (Ca2+) ions for their binding sites in cells and inhibit Ca2+ influx, whether Cd2+ weakens the immune responses of marine bivalves through inducing intracellular Ca2+ disorders still remains unclear. Therefore, the immunotoxicity of Cd2+ at different waterborne Ca2+ concentrations on blood clam, Tegillarca granosa, were investigated in the present study. Results obtained demonstrated that the total number, phagocytic activity, and red granulocytes ratio of the haemocytes were all significantly reduced after 10 days exposure of individuals to 25 μg/L Cd2+. However, when the waterborne Ca2+ concentrations were elevated by 10% and 20% (approximately 370 and 410 mg/L, respectively), mitigation effects on the immune responses of individuals were detected. In addition, though the expressions of genes from the Ca2+ signaling and Ca2+-related apoptosis pathways were significantly altered by Cd2+ exposure, the expression patterns of these genes were similar to that of the control when the waterborne Ca2+ concentrations were elevated, suggesting a relieving effect of waterborne Ca2+ on Cd2+ induced toxicity to haemocytes. The results obtained in the present study revealed that waterborne Cd2+ may hamper the immune responses of T. granosa through influencing Ca2+ signaling and Ca2+-related apoptosis pathways, which can be partially mitigated by elevating the waterborne Ca2+ concentrations.

A mutation in the progesterone receptor predisposes to HEV infection in HIV-positive patients.

Background and AimsInfection with Hepatitis E virus (HEV) can cause chronic liver disease in immunocompromised hosts. In transplant recipients, the use of certain immunosuppressants and food habits has been proposed as risk factors for HEV. In individuals infected with the human immunodeficiency virus (HIV), risk factors for HEV infection are less clear. We aimed to study the association between a mutation in the progesterone receptor (PR) named PROGINS and HEV‐infected in HIV‐positive individuals.MethodsWe evaluated the presence of the SNP PROGINS via KASP in serum samples of 64 HIV‐positive individuals and 187 healthy controls. We performed ELISA tests to address the serum levels of IL‐10 and IL‐12, as well as T‐cell stimulation assays in peripheral blood to address immune response in individuals with PROGINS.ResultsWe found a significant association between the presence of PROGINS mutation and HEV seroprevalence in individuals infected with HIV (30% in HIV+/HEV+ versus 2% in HIV+/HEV, respectively, P = .009). Moreover, we found that HIV+/HEV+ individuals expressing the PROGINS mutation had lower serum levels of IL‐10 and higher levels of IL‐12. The presence of the mutation led to a reduced response upon stimulation of CD4+ and CD8+ T cells compared to those without the mutation, suggesting an immune modulation associated with PROGINS.ConclusionsOur study identified a mutation in the PR that provides significant insights into mechanisms of HEV infection in immunosuppressed individuals.

Human cellular and humoral immune responses to Phlebotomus papatasi salivary gland antigens in endemic areas differing in prevalence of Leishmania major infection.

BackgroundSand fly saliva compounds are able to elicit specific immune responses that have a significant role in Leishmania parasite establishment and disease outcome. Characterizing anti-saliva immune responses in individuals living in well defined leishmaniasis endemic areas would provide valuable insights regarding their effect on parasite transmission and establishment in humans.Methodology/Principal findingsWe explored the cellular and humoral immune responses to Phlebotomus (P.) papatasi salivary gland extracts (SGE) in individuals living in cutaneous leishmaniasis (CL) old or emerging foci (OF, EF). OF was characterized by a higher infection prevalence as assessed by higher proportions of leishmanin skin test (LST) positive individuals compared to EF. Subjects were further subdivided into healed, asymptomatic or naïve groups. We showed anti-SGE proliferation in less than 30% of the individuals, regardless of the immune status, in both foci. IFN-γ production was higher in OF and only observed in immune individuals from OF and naïve subjects from EF. Although IL-10 was not detected, addition of anti-human IL-10 antibodies revealed an increase in proliferation and IFN-γ production only in individuals from OF. The percentage of seropositive individuals was similar in immune and naïves groups but was significantly higher in OF. No correlation was observed between anti-saliva immune responses and LST response. High anti-SGE-IgG responses were associated with an increased risk of developing ZCL. No differences were observed for anti-SGE humoral or cellular responses among naïve individuals who converted or not their LST response or developed or not ZCL after the transmission season.Conclusions/SignificanceThese data suggest that individuals living in an old focus characterized by a frequent exposure to sand fly bites and a high prevalence of infection, develop higher anti-saliva IgG responses and IFN-γ levels and a skew towards a Th2-type cellular response, probably in favor of parasite establishment, compared to those living in an emerging focus.

HYPERACTIVATION OF PI3 KINASE CAUSES DEFECTS IN HUMAN B-CELL DEVELOPMENT AND DIFFERENTIATION

Abstract Gain of function (GOF) mutations in PIK3CD, encoding the p110δ subunit of PI3-kinase, cause immune dysregulation characterized by recurrent respiratory infections, increased susceptibility to herpesvirus infection, lymphoma, organomegaly and autoimmunity. Affected individuals display poor Ab responses to protein and polysaccharide Ags suggesting defective humoral immune responses. To better understand humoral immune defects due to hyperactive PI3K, we analysed B cells in these individuals. In peripheral blood, transitional B cells were markedly increased while memory B cells were reduced. The phenotype of naïve B cells with PIK3CD GOF mutations resembled that of normal transitional B cells, indicating an aberrant arrest of developing B cells. Analysis of bone marrow revealed increased proportions of pro/pre-B cells and reduced recirculating mature B cells patients with PIK3CD GOF mutations. Within the memory B cell population there was a reduction in IgG+ cells. Consistent with this, there was a selective impairment in IgG production by transitional of naive B cells following in vitro stimulation. To extend these studies in vivo, we generated a mouse model using CRISPR/Cas9 to introduce the common disease-causing mutation (E1021K) into Pik3cd. Analysis of bone marrow from these mice revealed disrupted B-cell development. Investigation of Ag-specific T-dependent B cell responses using mice expressing a transgenic HEL-specific BCR combined with Pik3cd GOF allowed us to dissect defects in specific Ab generation that are seen in human PIK3CD GOF mutations. These results indicate that intrinsic defects in B-cell development and differentiation underlie poor humoral immune responses in individuals with PIK3CD GOF mutations.

HIV Controllers Exhibit Enhanced Frequencies of Major Histocompatibility Complex Class II Tetramer+ Gag-Specific CD4+ T Cells in Chronic Clade C HIV-1 Infection.

Immune control of viral infections is heavily dependent on helper CD4+ T cell function. However, the understanding of the contribution of HIV-specific CD4+ T cell responses to immune protection against HIV-1, particularly in clade C infection, remains incomplete. Recently, major histocompatibility complex (MHC) class II tetramers have emerged as a powerful tool for interrogating antigen-specific CD4+ T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4+ T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to the viral load of HIV-specific CD4+ T cell responses in a cohort of untreated HIV clade C-infected persons. We observed significantly higher frequencies of MHC class II tetramer-positive CD4+ T cells in HIV controllers than progressors (P = 0.0001), and these expanded Gag-specific CD4+ T cells in HIV controllers showed higher levels of expression of the cytolytic proteins granzymes A and B. Importantly, targeting of the immunodominant Gag41 peptide in the context of HLA class II DRB1*1101 was associated with HIV control (r = -0.5, P = 0.02). These data identify an association between HIV-specific CD4+ T cell targeting of immunodominant Gag epitopes and immune control, particularly the contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infection. Furthermore, these results highlight the advantage of the use of class II tetramers in evaluating HIV-specific CD4+ T cell responses in natural infections.IMPORTANCE Increasing evidence suggests that virus-specific CD4+ T cells contribute to the immune-mediated control of clade B HIV-1 infection, yet there remains a relative paucity of data regarding the role of HIV-specific CD4+ T cells in shaping adaptive immune responses in individuals infected with clade C, which is responsible for the majority of HIV infections worldwide. Understanding the contribution of HIV-specific CD4+ T cell responses in clade C infection is particularly important for developing vaccines that would be efficacious in sub-Saharan Africa, where clade C infection is dominant. Here, we employed MHC class II tetramers designed to immunodominant Gag epitopes and used them to characterize CD4+ T cell responses in HIV-1 clade C infection. Our results demonstrate an association between the frequency of HIV-specific CD4+ T cell responses targeting an immunodominant DRB1*11-Gag41 complex and HIV control, highlighting the important contribution of a single class II MHC-peptide complex to the immune response against HIV-1 infections.

<i>Schistosoma mansoni</i> Infection: A Major Contributor of Reduced Effective T Helper Responses against <i>Plasmodium falciparum</i> and <i>Schistosoma mansoni</i> Co-Infection in <i>ex vivo</i>: A Cross-Sectional Study to Assess Th1, Th2 & Th17 Immune Responses

Background: Parasitic worms evade immune responses, and interactions between diseases can cause altered immunologic outcomes compared to what usually occurs with single infections. These interactions may influence vaccine and chemotherapeutic efficacy. Schistosoma mansoni and Plasmodium falciparum are co-endemic in Uganda and are the leading parasitic causes of public health problems across sub-Saharan Africa. Objectives: The overall aim was therefore, to elucidate the impact of S. mansoni infection on protective T helper immune responses on P. falciparum and S. mansoni co-infection. Methodology: This study evaluated the T helper immune responses in individuals with independent S. mansoni infection, independent P. falciparum infection, co-infection and non-infection in school attending children in a co-endemic area along Lake Victoria shores, Uganda. Immune responses were categorized into Th1, Th2, and Th17 based on unique cytokine(s) produced by the T helper subpopulation in ex vivo. Kato Katz thick smears and circulating cathodic antigen tests were performed for S. mansoni screening, whereas thick and thin blood smear techniques were performed for P. falciparum screening. Results: We observed an up regulated Th1 T helper subpopulation in independent P. falciparum infections compared to the uninfected group. Suboptimal T helper immune responses were detected in independent S. mansoni infections characterized by significantly down regulated Th1 (Z = -1.425, p = 0.0313) response in comparison to the non-infected group. Suboptimal T helper immune responses were also recorded in the co-infected individuals characterized by significantly down regulated Th1 (Z = -3.260, p = 0.0273) and Th2 (Z = -1.180, p = 0.0078) responses compared to independent P. falciparum. Conclusions: S. mansoni infection is a major contributor of a reduced effective T helper immune response against P. falciparum in P. falciparum and S. mansoni co-infection.

Suicide attempts and markers of immune response in individuals with serious mental illness

Previous studies have identified elevations in antibodies to Toxoplasma gondii in individuals with a history of suicide attempts but studies have not measured the association between suicide attempts and a panel of antibody markers. We assessed 162 patients receiving treatment for schizophrenia, bipolar disorder, or major depression on the Columbia Suicide Severity Rating Scale for suicide attempt history and other clinical measures. All participants had a blood sample drawn from which were measured antibodies to Toxoplasma gondii and other neurotropic infectious agents. A total of 72 (44%) of participants had a lifetime suicide attempt; these individuals had elevated levels of IgM class antibodies to Toxoplasma gondii and Cytomegalovirus (CMV). We also found an association between the levels of these antibodies and the number of suicide attempts. There was a particularly strong odds of a suicide attempt history in individuals who had elevated levels of IgM antibodies to both Toxoplasma gondii and to CMV suggesting an additive risk associated with the antibodies. These findings remained significant when adjusting for current cigarette smoking and history of drug/alcohol use which were also associated with suicide attempts. We did not find an association between a suicide attempt history and IgG class antibodies to Toxoplasma gondii, CMV, or IgM or IgG antibodies to the Epstein Barr Virus or other antigens tested. The identification of blood-based antibody markers should provide for more personalized methods for the assessment and treatment, and ultimately prevention, of suicide attempts in individuals with serious mental illnesses.

A Frameshift in CSF2RB Predominant Among Ashkenazi Jews Increases Risk for Crohn's Disease and Reduces Monocyte Signaling via GM-CSF

Crohn's disease (CD) has the highest prevalence in Ashkenazi Jewish populations. We sought to identify rare, CD-associated frameshift variants of high functional and statistical effects. We performed exome sequencing and array-based genotype analyses of 1477 Ashkenazi Jewish individuals with CD and 2614 Ashkenazi Jewish individuals without CD (controls). To validate our findings, we performed genotype analyses of an additional 1515 CD cases and 7052 controls for frameshift mutations in the colony-stimulating factor 2-receptor β common subunit gene (CSF2RB). Intestinal tissues and blood samples were collected from patients with CD; lamina propria leukocytes were isolated and expression of CSF2RB and granulocyte-macrophage colony-stimulating factor-responsive cells were defined by adenomatous polyposis coli (APC) time-of-flight mass cytometry (CyTOF analysis). Variants of CSF2RB were transfected into HEK293 cells and the expression and functions of gene products were compared. In the discovery cohort, weassociated CD with a frameshift mutation in CSF2RB (P=8.52× 10(-4)); the finding was validated in the replication cohort (combined P= 3.42× 10(-6)). Incubation of intestinal lamina propria leukocytes with granulocyte-macrophage colony-stimulating factor resulted in high levels of phosphorylation of signal transducer and activator of transcription (STAT5) and lesser increases in phosphorylation of extracellular signal-regulated kinase and AK straining transforming (AKT). Cells co-transfected withfull-length and mutant forms of CSF2RB had reduced pSTAT5 after stimulation with granulocyte-macrophage colony-stimulating factor, compared with cells transfected with control CSF2RB, indicating a dominant-negative effect of the mutant gene. Monocytes from patients with CD who were heterozygous for the frameshift mutation (6% of CD cases analyzed) hadreduced responses to granulocyte-macrophage colony-stimulating factor and markedly decreased activity of aldehyde dehydrogenase; activity of this enzyme has been associated with immune tolerance. In a genetic analysis of Ashkenazi Jewish individuals, we associated CD with a frameshift mutation in CSF2RB. Intestinal monocytes from carriers of this mutation had reduced responses to granulocyte-macrophage colony-stimulating factor, providing an additional mechanism for alterations to the innate immune response in individuals with CD.

Vegetal extracts influence in vitro on the cell-mediated immunity in carnivores depending on health status, target species and plant taxonomy

Impaired immune response in individuals subjected to various stress factors leads to disease or low protective responses following vaccination, therefore modern immunology is seeking for alternative immune stimulating compounds for which plants could represent a source. The aim of this study was to establish the influence of several ethanolic vegetal extracts on in vitro adaptive cell-mediated reactivity in wild (mink, n=70, silver foxes, n=22) and domestic (dogs, n=32) carnivores and compare the responsiveness of these species under physiological (antigen-primed) and pathophysiological (aleutian disase of mink) conditions. Mink and foxes were primed with a 5% SRBC suspension (0.5 and 1ml respectively), twice, 14days apart and blood was sampled on days 0 and 14, while untreated dogs were sampled only once. Ethanolic extracts of Calendula officinalis, Symphytum officinale, Arnica montana, Echinaceea angustifolia and Echinacea purpurea were tested for immune activity in whole blood cultures by the use of the in vitro blast transformation test, where cell growth was monitored spectrophotometrically, by the glucose consumption test and stimulation/inhibition indices (S/I) were calculated.E. angustifolia acted stimulating in Aleutian disease positive mink (S/I SRBC primed 76.75±12.52%, non-primed 19.58±18.07, p<0.001) and foxes (S/I primed 20.28±21.27%, non-primed 20.13±13.10), while S. officinale was most stimulating (3.85±1.37%) in dogs in a statistically supported manner (p<0.05).In conclusion, the results indicated the need of individualized immune stimulating therapies, based on species and health status in the studied species, with the prior identification of the most appropriate plant alcoholic extract for each species.

Crohn's Disease: Evolution, Epigenetics, and the Emerging Role of Microbiome-Targeted Therapies.

Crohn's disease (CD) is a chronic, systemic, immune-mediated inflammation of the gastrointestinal tract. Originally described in 1932 as non-caseating granulomatous inflammation limited to the terminal ileum, it is now recognized as an expanding group of heterogeneous diseases defined by intestinal location, extent, behavior, and systemic extraintestinal manifestations. Joint diseases, including inflammatory spondyloarthritis and ankylosing spondylitis, are the most common extraintestinal manifestations of CD and share more genetic susceptibility loci than any other inflammatory bowel disease (IBD) trait. The high frequency and overlap with genes associated with infectious diseases, specifically Mendelian susceptibility to mycobacterial diseases (MSMD), suggest that CD may represent an evolutionary adaptation to environmental microbes. Elucidating the diversity of the enteric microbiota and the protean mucosal immune responses in individuals may personalize microbiome-targeted therapies and molecular classifications of CD. This review will focus on CD's natural history and therapies in the context of epigenetics, immunogenetics, and the microbiome.

Characterization of clinical and immunological features in patients coinfected with dengue virus and HIV

The pathogenesis of dengue in subjects coinfected with HIV remains largely unknown. We investigate clinical and immunological parameters in coinfected DENV/HIV patients. According to the new dengue classification, most coinfected DENV/HIV patients presented mild clinical manifestations of dengue infection. Herein, we show that DENV/HIV coinfected patients had higher CD8 T cells percentages reflected as a lower CD4/CD8 ratio. Furthermore, CCR5 expression on CD4 T cells and CD107a expression on both T subsets were significantly higher in coinfected patients when compared with monoinfected DENV and HIV individuals respectively. Increased inflammatory response was observed in treated HAART coinfected patients despite undetectable HIV load. These data indicate that DENV infection may influence the clinical profile and immune response in individuals concomitantly infected with HIV.

Individuals with inherited chromosomally integrated human herpes virus 6 (ciHHV-6) have functionally active HHV-6 specific T-cell immunity

To evaluate the human herpes virus 6 (HHV-6) -specific immune response in individuals with chromosomally integrated HHV-6 (ciHHV-6), we measured HHV-6-antigen-specific cytokine responses (interferon-γ, interleukin-2, tumour necrosis factor-α) in T cells by flow cytometry in 12 and 16 individuals with and without ciHHV-6, respectively. All individuals with ciHHV-6 showed HHV-6-specific T cells with higher frequencies of HHV-6-specific CD8+ cells (0.03–14.93, median 2.15% of CD8+ cells) compared with non-ciHHV-6 (0.0–10.67, median 0.36%, p 0.026). The observed increased HHV-6-specific functionally active responses in individuals with ciHHV-6 clearly disprove speculations on immune tolerance in ciHHV-6 and indicate clinical and immunological implications of ciHHV-6.

Associations between hepcidin and immune response in individuals with hyperbilirubinaemia and severe malaria due to Plasmodium vivax infection.

BackgroundHyperbilirubinaemia (bilirubin >51.3 μmol/L) alone is not indicative of severe malaria, and the immune response underlying hyperbilirubinaemia remains largely unexplored. Liver damage associated with hyperbilirubinaemia may alter the expression of hepcidin, which regulates systemic iron by degrading ferroportin. For this study, the association between hepcidin and the levels of cytokines and chemokines in the serum of individuals with mild and severe vivax malaria and subjects with malaria with isolated hyperbilirubinaemia was evaluated.MethodsCytokines/chemokines and hepcidin were measured in individuals with mild (n = 72) and severe (n = 17) vivax malaria, as well as in the serum of subjects with vivax malaria with isolated hyperbilirubinaemia (n = 14) from the Brazilian Amazon between 2009 and 2013 by multiplex assay and ELISA, respectively. The polymorphism 744 G > T in the ferroportin gene was identified by restriction fragment-length polymorphism analysis and the restriction enzyme PvuII.ResultsThe polymorphism at position 744 G > T in the ferroportin gene was typed and no differences in the distributions of genotypes or alleles were observed between the study groups. Subjects with severe malaria had higher levels of interleukin (IL)-2 and IL-13 than subjects with hyperbilirubinaemia. No differences in the expression of immune markers were observed between subjects with mild malaria and those with hyperbilirubinaemia. However, hepcidin levels were higher in individuals with severe malaria and hyperbilirubinaemia than those with mild malaria (p = 0.0002 and p = 0.0004, respectively) and cut-off values of hepcidin differentiated these groups from subjects with mild malaria. Hepcidin was positively associated with IL-6 and IL-10 levels and with parasitaemia in subjects with mild malaria and with IFN-γ in subjects with severe malaria.ConclusionsMalaria in the presence of hyperbilirubinaemia produces a less robust inflammatory response compared to severe cases of malaria. Hepcidin levels are positively associated with immune markers in vivax malaria outcomes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12936-015-0930-x) contains supplementary material, which is available to authorized users.

Impact of Fighting on Antibody Response to Hepatitis B Virus Vaccine in Mice.

Antibody responses to vaccines can be influenced by various behavioral and psychosocial factors. Few reports exist on the impact of fighting on antibody response to vaccines. This study unexpectedly found that fighting could significantly enhance antibody production in male mice immunized with hepatitis B virus (HBV) vaccines. To confirm the finding, a mouse-fighting model was established in which it was observed that only intense fighting, not mild fighting, enhanced the antibody response to HBV surface antigen in male mice, and that the frequency of fighting and active attacks during fighting showed no obvious relationship with the antibody levels in the male mice that experienced fighting. In addition, fighting can cause significant upregulation of CD80 in CD11c(+) cells in the spleen of male mice. These data suggest that fighting could influence the humoral immune response in individuals immunized with vaccines or infected with microbes.

Similar protective immunity induced by an inactivated enterovirus 71 (EV71) vaccine in neonatal rhesus macaques and children

During the development of enterovirus 71 (EV71) inactivated vaccine for preventing human hand, foot and mouth diseases (HFMD) by EV71 infection, an effective animal model is presumed to be significant and necessary. Our previous study demonstrated that the vesicles in oral regions and limbs potentially associated with viremia, which are the typical manifestations of HFMD, and remarkable pathologic changes were identified in various tissues of neonatal rhesus macaque during EV71 infection. Although an immune response in terms of neutralizing antibody and T cell memory was observed in animals infected by the virus or stimulated by viral antigen, whether such a response could be considered as an indicator to justify the immune response in individuals vaccinated or infected in a pandemic needs to be investigated. Here, a comparative analysis of the neutralizing antibody response and IFN-γ-specific T cell response in vaccinated neonatal rhesus macaques and a human clinical trial with an EV71 inactivated vaccine was performed, and the results showed the identical tendency and increased level of neutralizing antibody and the IFN-γ-specific T cell response stimulated by the EV71 antigen peptide. Importantly, the clinical protective efficacy against virus infection by the elicited immune response in the immunized population compared with the placebo control and the up-modulated gene profile associated with immune activation were similar to those in infected macaques. Further safety verification of this vaccine in neonatal rhesus macaques and children confirmed the potential use of the macaque as a reliable model for the evaluation of an EV71 candidate vaccine.

Long-Term Immunogenicity and Safety of a Conventional Influenza Vaccine in Patients with Type 2 Diabetes.

No previous studies have assessed the persistence of immune responses in individuals with diabetes. We conducted this study to evaluate the long-term immunogenicity and safety of an influenza vaccine in type 2 diabetic subjects compared with nondiabetic controls. A randomized and controlled study was conducted at two university hospitals during the 2012-2013 influenza season. The study vaccine was a standard-dose trivalent subunit inactivated intramuscular vaccine. Serum hemagglutination-inhibiting (HI) antibodies were measured at the time of vaccination and 1 month and 6 months after vaccination. Local and systemic reactions were recorded for 7 days. A total of 105 diabetic patients and 108 controls were included in the analysis. One month after vaccination, both the diabetic and nondiabetic groups satisfied all of the criteria of the Committee for Medical Products for Human Use (CHMP), and the immunogenicity profiles were statistically similar between the two groups. Although the vaccine was well tolerated, and all adverse reactions were mild to moderate, there was a tendency toward a reduced incidence of local reactions in the diabetic group. All values in the long-term immunogenicity profiles were statistically similar between the two groups, except for the seroprotection rate for the A/H1N1 influenza virus strain, which was significantly lower in the elderly diabetic group than that in the elderly nondiabetic group. However, in multivariate analysis, long-term immunogenicity was associated with age and prevaccination titer, regardless of diabetes status. (This study has been registered at CRIS [https://cris.nih.go.kr/cris/en/] under registration no. KCT0001423.).

Antibodies to post-translationally modified insulin in type 1 diabetes.

Insulin is the most specific beta cell antigen and a potential primary autoantigen in type 1 diabetes. Insulin autoantibodies (IAAs) are the earliest marker of beta cell autoimmunity; however, only slightly more than 50% of children and even fewer adults newly diagnosed with type 1 diabetes are IAA positive. The aim of this investigation was to determine if oxidative post-translational modification (oxPTM) of insulin by reactive oxidants associated with islet inflammation generates neoepitopes that stimulate an immune response in individuals with type 1 diabetes. oxPTM of insulin was generated using ribose and various reactive oxygen species. Modifications were analysed by SDS-PAGE, three-dimensional fluorescence and MS. Autoreactivity to oxPTM insulin (oxPTM-INS) was observed by ELISA and western blotting, using sera from participants with type 1 or type 2 diabetes and healthy controls as probes. IAA was measured using the gold-standard radiobinding assay (RBA). MS of oxPTM-INS identified chlorination of Tyr16 and Tyr26; oxidation of His5, Cys7 and Phe24; and glycation of Lys29 and Phe1 in chain B. Significantly higher binding to oxPTM-INS vs native insulin was observed in participants with type 1 diabetes, with 84% sensitivity compared with 61% sensitivity for RBA. oxPTM-INS autoantibodies and IAA co-existed in 50% of those with type 1 diabetes. Importantly 34% of those with diabetes who were IAA negative were oxPTM-INS positive. Altogether, 95% of participants with type 1 diabetes presented with autoimmunity to insulin by RBA, oxPTM-INS or both. Binding to oxPTM-INS was directed towards oxPTM-INS fragments with slower mobility than native insulin. These data suggest that oxPTM-INS is a potential autoantigen in individuals with new-onset type 1 diabetes.

INVESTIGAÇÃO DO TRATAMENTO COM O BENZONIDAZOL SOBRE A RESPOSTA IMUNOLÓGICA DE PORTADORES CRÔNICOS DA DOENÇA DE CHAGAS

Evidence suggests that benznidazole treatment directly interferes withthe host immune response in the chronic phase of Chagas disease. However,a longitudinal study to simultaneously evaluate immune parameters related toactivation, cytotoxicity, cell regulation and inflammation of these chronic patientssubmitted to etiological treatment has never been performed. Therefore, the presentstudy aimed to evaluate immune response in individuals with chronic Chagasdisease before and after benznidazole treatment. Twenty-one adults classifiedas in the chronic phase of Chagas disease (indeterminate form-IND=13/cardiacform-CARD=8) were selected. Blood samples were collected before etiologicaltreatment (T0/n=21), after 2-3 months (T1/n=21) and after 5-6 months (T2/n=16),which were analyzed by flow cytometry. Increase in CD5+CD19+ B1 lymphocytes,as well as greater activation of cytotoxic T CD8+ cells (CD28+), indicated thatbenznidazole exacerbates cellular mechanisms related to Trypanosoma cruzielimination. On the other hand, there was a reduction in IFN-g production by T and Blymphocytes in all individuals. These phenomena associated with a low percentageof CD4+CD25+/highFoxP3+ T lymphocytes, suggest a loss of the mechanismsagainst the parasite and to control inflammatory response. It was emphasized thatthe rise of a modulated Th1 cytokine pattern (inflammatory: IFN-g / regulatory:IL-4, IL-6, IL-10) delayed (T2) in the IND+CARD group may indicate that after aninitial immune imbalance, host response would become immunomodulatory. Thus,benznidazole acts by unbalancing different mechanisms related to immune responsein chronic Chagas disease. A long follow-up investigation will be necessary toconclude if these phenomena are definitive or are due to high levels of drug andantigen in the host organism.