Increased IgG Levels Research Articles

Chronic infection and inflammation affect exercise capacity in cystic fibrosis

Pulmonary function and nutritional status are important determinants of exercise capacity in patients with cystic fibrosis (CF). Studies investigating the effects of determinants, such as genotype or infection and inflammation, are scarce and have never been analysed in a multivariate longitudinal model. A prospective longitudinal cohort study was performed to evaluate whether genotype, chronic inflammation and infection were associated with changes in exercise capacity. Furthermore, we investigated whether exercise capacity can predict clinical outcome. 504 exercise tests of 149 adolescents with CF were evaluated. Maximal oxygen uptake corrected for body mass % predicted declined 20% during adolescence, and was associated with immunoglobulin (Ig)G levels and chronic Pseudomonas aeruginosa infection. A lower exercise capacity was associated with a higher mortality, steeper decline in pulmonary function and greater increase in IgG levels. Since a decline in exercise capacity during adolescence was negatively associated with IgG levels and chronic P. aeruginosa infection, these data emphasise the importance of prevention and treatment of chronic inflammation and infections in patients with CF. Furthermore, a lower exercise capacity was associated with a higher mortality rate, steeper decline in pulmonary function and higher increase in IgG levels with increasing age in adolescents with CF. This stresses the value of regular exercise testing for assessing prognosis in adolescents with CF.

The Influence of Membrane Molecular Weight Cutoff on a Novel Bioartificial Liver

Given the xenogeneic immune reaction relevant to the molecular weight cutoff of the membrane of a bioartificial liver (BAL) system, we investigated the influence of membrane molecular weight cutoff in our BAL system in this study. Acute liver failure in beagles was induced by d-galactosamine administration. Eight beagles were divided into two groups by the membrane molecular weight cutoff of the plasma component separator. Group 1 beagles were treated with BAL containing 200 kDa retention rating membrane. Group 2 beagles were treated with BAL containing 1200 kDa retention rating membrane. Each group underwent two 6-h BAL treatments that were performed on day 1 and day 21. The hemodynamic and hematologic response, humoral immune responses, and cytotoxic immune response to BAL therapy were studied before and after treatments. All beagles remained hemodynamically and hematologically stable during BAL treatments. BAL treatment was associated with a significant decline in levels of complement; however, a longer time of level maintenance was observed in Group 2. Group 2 beagles experienced a significant increase in levels of IgG and IgM after two BAL treatments. Significant levels of canine proteins were detected in BAL medium from Group 2; only trace levels of canine proteins were detected in BAL medium from Group 1. The posttreatment viability of co-culture cells in Group 2 was lower compared with Group 1, and the viability of co-culture cells after treatments was associated with deposition of canine proteins on the cells. Xenogeneic immune response was influenced by membrane molecular weight cutoff in the BAL.

The effects of propolis on antibody production by laying hens

Propolis is a honeybee product showing several biological properties that enhance the immune response, depending on the concentration and intake period. Because propolis possesses an immunomodulatory action on mammals, the objective of our study was to investigate the effects of propolis on the humoral immune response of laying hens by evaluating antibody production. Laying hens (ISA Brown) were divided into 5 groups with 7 birds each. Group 1 was a nonimmunized control, whereas birds in group 2 were immunized intravenously with SRBC, and those in groups 3, 4, and 5 were treated intraperitoneally with propolis (2, 10, and 50 mg/kg, respectively) on 3 consecutive days and then inoculated intravenously with SRBC. Hematological and serological analyses were carried out on d 0, 3, and 38. Natural and specific antibody levels were determined by hemagglutination with rabbit red blood cells and SRBC, respectively. Propolis-treated birds (50 mg/kg) showed a significant decline in heterophils and in the heterophil:lymphocyte ratio. After SRBC immunization, significant increases in levels of IgG were observed in groups 4 and 5. Furthermore, higher levels of natural antibodies were observed in propolis-treated laying hens. The administration of propolis to laying hens increased the production of IgG specific to SRBC and natural antibodies, and could be used to increase antigen-specific antibody responses to vaccines.

Allergen-specific IgG antibody levels modify the relationship between allergen-specific IgE and wheezing in childhood

An increase in IgE antibody levels to inhalant allergens is associated with an increased likelihood of wheezing. The role of allergen-specific IgG and IgG4 in relation to wheezing is yet to be determined. We sought to investigate whether Fel d 1-specific IgG and IgG4 antibodies modify the association between cat allergen-specific IgE and childhood wheezing. We used data from 2 population-based birth cohorts (United Kingdom [UK], n= 473; Australia, n= 1336). Current wheeze was defined as wheezing in the previous 12 months at age 5 (UK) and 14 (Australia) years. We determined cat allergen-specific IgE (whole extract) and IgG and IgG4 antibody (purified rFel d 1) levels and used logistic regression to estimate the relationship between wheeze and the quantitative allergen antibody levels. In the univariate analysis risk of wheezing increased significantly with increasing cat-specific IgE levels (UK: odds ratio [OR], 1.56; 95% CI, 1.28-1.90; Australia: OR, 1.29; 95% CI, 1.19-1.40). rFel d 1-specific IgG or IgG4 had no significant effect on wheeze in either population. However, a different pattern of the relationship between antibody levels and wheezing emerged in the multivariate analysis. In the UK cat-specific IgE increased the risk of wheeze (OR, 2.01; 95% CI, 1.29-3.12; P= .002), whereas rFel d 1-specific IgG decreased the risk (OR, 0.46; 95% CI, 0.21-0.99; P= .05). This finding wasreplicated in Australia (IgE: OR, 1.46; 95% CI, 1.28-1.68; P< .001; IgG: OR, 0.66; 95% CI, 0.44-0.99; P= .049). There was no significant association between IgG4 antibody levels and wheezing in either population. rFel d 1-specific IgG but not IgG4 antibody levels significantly modify the association between cat-specific IgE and childhood wheezing, with the risk of symptoms decreasing with increasing IgG levels.

A whey-based glutathione-enhancing diet decreases allergen-induced airway contraction in a guinea-pig model of asthma

Since an allergen-induced early asthmatic reaction is likely to be accompanied by oxidative stress and since levels of the endogenous antioxidant glutathione can be enhanced by a whey-based diet (undenatured whey protein concentrate, UWPC), it was investigated whether UWPC could alleviate allergen-induced lung contractions. Guinea pigs were fed water or UWPC twice a day starting at day - 3 up to day 20. The animals were sensitised to ovalbumin or received saline on day 0. Serum samples were taken at several days after sensitisation to measure allergen-specific IgG. On day 20, lungs were isolated and perfused with buffer containing the allergen ovalbumin. Airway contractions were assessed, and mediators and indicators for oxidative stress were measured in the lung effluent. Moreover, glutathione levels were determined in the liver. The indicator of oxidative stress and airway contractile mediator, 8-iso-PGF(2α), was increased upon ovalbumin challenge in ovalbumin-sensitised groups. Furthermore, thiobarbituric acid-reactive substances (TBARS) were increased as well. Sensitisation with ovalbumin increased IgG levels from day 12 up to day 20, which were not influenced by the UWPC diet. In contrast, the UWPC diet significantly enhanced glutathione levels in the liver. Moreover, the UWPC diet significantly reduced the ovalbumin-induced anaphylactic response by 45 % and decreased PGE2 levels by 55 % in the effluent fluid. We show for the first time that during anaphylaxis, there is acute oxidative stress in the respiratory tract. The UWPC diet did not influence the sensitisation response to the allergen but did increase endogenous glutathione levels. The UWPC diet profoundly reduces allergen-induced airway constrictions, which opens new avenues for dietary management of allergic diseases.

Autoimmune Lebererkrankungen

Autoimmune liver diseases in children and adolescents include autoimmune hepatitis, autoimmune cholangitis, and sclerosing cholangitis. The etiology is widely unknown. Besides mostly uncharacteristic clinical symptoms diagnostic criteria are elevated aminotransferases, hypergammaglobulinemia, increased IgG level, and the presence of specific autoantibodies. Additionally histological investigation of liver tissue is mandatory. A considerable number of patients show severe liver fibrosis or beginning liver cirrhosis at diagnosis. Early diagnosis is most important, because immediate immunosuppressive treatment may prevent rapid progression of liver disease. Immunosuppressive treatment is still based on the combination of prednisolone and azathioprine. In cases without remission cyclosporin or mycophenolate mofetil can be administered. In most cases long-term treatment is necessary, as relapses are common. Only in 20% of treated subjects may therapy be successfully stopped. In 8–10% of patients liver transplantation may be indicated 15 years after diagnosis.

Effect of allergen-specific immunotherapy with purified Alt a1 on AMP responsiveness, exhaled nitric oxide and exhaled breath condensate pH: a randomized double blind study

BackgroundLittle information is available on the effect of allergen-specific immunotherapy on airway responsiveness and markers in exhaled air. The aims of this study were to assess the safety of immunotherapy with purified natural Alt a1 and its effect on airway responsiveness to direct and indirect bronchoconstrictor agents and markers in exhaled air.MethodsThis was a randomized double-blind trial. Subjects with allergic rhinitis with or without mild/moderate asthma sensitized to A alternata and who also had a positive skin prick test to Alt a1 were randomized to treatment with placebo (n = 18) or purified natural Alt a1 (n = 22) subcutaneously for 12 months. Bronchial responsiveness to adenosine 5'-monophosphate (AMP) and methacholine, exhaled nitric oxide (ENO), exhaled breath condensate (EBC) pH, and serum Alt a1-specific IgG4 antibodies were measured at baseline and after 6 and 12 months of treatment. Local and systemic adverse events were also registered.ResultsThe mean (95% CI) allergen-specific IgG4 value for the active treatment group increased from 0.07 μg/mL (0.03-0.11) at baseline to 1.21 μg/mL (0.69-1.73, P < 0.001) at 6 months and to 1.62 μg/mL (1.02-2.22, P < 0.001) at 12 months of treatment. In the placebo group, IgG4 value increased nonsignificantly from 0.09 μg/mL (0.06-0.12) at baseline to 0.13 μg/mL (0.07-0.18) at 6 months and to 0.11 μg/mL (0.07-0.15) at 12 months of treatment. Changes in the active treatment group were significantly higher than in the placebo group both at 6 months (P < 0.001) and at 12 months of treatment (P < 0.0001). However, changes in AMP and methacholine responsiveness, ENO and EBC pH levels were not significantly different between treatment groups. The overall incidence of adverse events was comparable between the treatment groups.ConclusionAlthough allergen-specific immunotherapy with purified natural Alt a1 is well tolerated and induces an allergen-specific IgG4 response, treatment is not associated with changes in AMP or methacholine responsiveness or with significant improvements in markers of inflammation in exhaled air. These findings suggest dissociation between the immunotherapy-induced increase in IgG4 levels and its effect on airway responsiveness and inflammation.

Improving the Immunogenicity of Pneumococcal Conjugate Vaccine in HIV‐Infected Adults with a Toll‐Like Receptor 9 Agonist Adjuvant: A Randomized, Controlled Trial

Persons infected with human immunodeficiency virus (HIV) are often hyporesponsive to immunization, including pneumococcal vaccines. We hypothesized that adding CPG 7909, a toll-like receptor 9 (TLR9) agonist and vaccine adjuvant, to 7-valent pneumococcal conjugate vaccine (7vPnC) would increase its immunogenicity in HIV-infected adults. We performed a double-blind, placebo-controlled, phase 1b/2a trial randomizing HIV-positive patients to receive double doses of 7vPnC (Prevnar) at 0 and 3 months and 1 dose of 23-valent pneumococcal polysaccharide vaccine (PPV-23; Pneumo Novum) at 9 months, with experimental patients receiving 1 mg of CPG 7909 added to each of their 3 vaccine doses; control patients had phosphate-buffered saline added instead. Immunogenicity and safety were evaluated for up to 10 months. The primary end point was the proportion of vaccine high responders at 9 months, defined as a 2-fold increase in IgG levels to > or = 1 microg/mL for at least 5 of 7 of the 7vPnC serotypes. Ninety-seven participants were included in the study. The proportion of vaccine high responders was higher in the experimental group (n = 48) than among controls (n = 49; 48.8% vs 25.0%; P = .02) at 9 months. Greater proportions of high responders were also observed at 3 (51.1% vs 39.6%; P = .26), 4 (77.3% vs 56.3%; P = .03), and 10 months (87.8% vs 51.1%; P < .001). Mild systemic and injection site reactions to 7vPnC were more common in the experimental group than the control group (100% vs 81.3%; P = .002). CPG 7909 did not increase non-7vPnC IgG levels after PPV-23 immunization. No adverse effects on CD4(+) cell count or organ functions occurred in either group. The addition of a TLR9 agonist to 7vPnC significantly enhanced the proportion of vaccine high responders. ClinicalTrials.gov identifier: NCT00562939 .

Assessment of immunological biomarkers in patients with advanced cancer treated by personalized peptide vaccination.

e13043 Background: To investigate immunological biomarkers to predict overall survival of advanced cancer patients under treatment with personalized peptide vaccination. Methods: Between October 2000 and October 2008, pre- and post- (sixth) vaccination peripheral blood lymphocytes and plasma from 500 advanced cancer patients under treatment with personalized peptide vaccination were analyzed for measurement of cytotoxic T lymphocyte (CTL) activity and IgG reactive to the vaccinated peptides, respectively. All 500 patients suffered from advanced cancer originating in the prostate (n = 174), colon and rectum (n = 74), pancreas (n = 50), stomach (n = 42), brain (n = 33), uterus (n = 28), lung (n = 22), kidney (n = 13), skin (n = 12), breast (n = 11), bladder and urinary tracts (n = 10), and elsewhere (n = 31).Correlations between overall survival and CTL or IgG response were investigated statistically. Results: The best clinical responses were for 43 PR, 144 SD, and 249 PD with a median overall survival of 9.9 months. Increased CTL or IgG response to at least one of the vaccinated peptides was observed in 199 of 332 (60%) or 187 of 300 (62%) patients tested, respectively. IgG response (P = 0.0015) was superior to CTL response (p = 0.167) with regard to correlation with overall survival. To statistically confirm the superiority of IgG response, the samples from advanced hormone-refractory prostate cancer patients (n = 20) who survived more than 900 days and those from those (n = 23) who died within 300 days were analyzed further. As a result, the number of peptides and the increase in IgG levels were found to be significantly higher in long-term survivors (p = 0.000282 and p = 0.00045, respectively). In contrast, those of CTL responses were not statistically different between the two groups. Conclusions: The measurement of IgG response was suggested as an immunological biomarker for prediction of the overall survival of advanced cancer patients under treatment with personalized peptide vaccination. No significant financial relationships to disclose.

A phase II study of personalized selection of peptide vaccines combined with conventional chemo- or endocrine therapy for refractory breast cancer.

TPS173 Background: Immunotherapy using selected personalized peptide vaccines (PPV) has been reported to be effective for boosting anticancer immunity in many patients (pts) even in an advanced status. This study evaluate the anti-tumor immunologic effect and safety of PPV for pts with refractory breast cancer. Methods: Patient eligibility criteria: all patients had histologically confirmed measurable metastatic breast cancer and their HLA A molecules should be each of HLA-A2, A3, A11, A24, A26, A31 or A33. The following criteria were also required: age > 20 years, life expectancy of at least 3 months, ECOG performance status of 0 or 1, adequate vital organ function (WBC > 2,500/μ L; platelets > 80,000/μ L; serum creatinine < 1.5 mg/dL or creatinine clearance > 50 mL/min; AST and ALT < 2 times the upper limit of the institution's normal range; and total bilirubin < 2.5 mg/dL. All subjects provided written informed consent and the clinical protocol was approved by each institutional review board before patient enrollment. Treatment schedule:Pre- vaccination plasma was measured for their IgG levels reactive to each of the previously reported 31 candidate peptides followed by administration subcutaneously of the four peptides at maximum showing higher levels of IgG in order with schedule of every 1-2 week for a total of 6-24 doses. The concurrent conventional chemotherapy or endocrine therapy was available for the combination of PPV. Study design: This is an open-label, multicenter, single-arm, phase II study. The primary endpoint was anti-tumor immunologic effect and safety, and the secondary endpoints were clinical responses. The planned sample size was 60-80. Immune and clinical response assessment : Levels of IgG reactive to each of the 31 peptides in the pre- and post-treatment plasma at every 6 times of vaccination were measured using LUMNEX system. Clinical response was evaluated by RECIST criteria. Correlation between overall survival and the increased IgG levels was also investigated. No significant financial relationships to disclose.

Allergen immunotherapy

Specific immunotherapy (SIT) involves the administration of allergen extracts to achieve clinical tolerance of those allergens that cause symptoms in patients with allergic conditions. Immunotherapy is effective in patients with mild forms of allergic disease and also in those who do not respond well to standard drug therapy. Most SIT is given by means of injection, but there is increasing interest in performing SIT through the sublingual route. SIT remains the treatment of choice for patients with systemic allergic reactions to wasp and bee stings and should be considered as an option in patients with allergic rhinitis, asthma, or both. SIT can modify the course of allergic disease by reducing the risk of new allergic sensitizations and inhibiting the development of clinical asthma in children treated for allergic rhinitis. The precise mechanisms responsible for the beneficial effects of SIT remain a matter of research and debate. An effect on regulatory T cells seems most probable and is associated with switching of allergen-specific B cells toward IgG4 production. Few direct comparisons of SIT and drug therapy have been made. Existing data suggest that the effects of SIT take longer to develop, but once established, SIT achieves long-lasting relief of allergic symptoms, whereas the benefits of drugs only last as long as they are continued.

Immunization of pregnant sows with a novel virulence gene deleted live Salmonella vaccine and protection of their suckling piglets against salmonellosis

This study was carried out to examine a novel Salmonella Typhimurium ( S. Typhimurium) vaccine for protection of suckling piglets against salmonellosis by immunization of pregnant sows using various administration routes. The vaccine strain was constructed by deletion of cpxR and lon from a wild type S. Typhimurium and the S. Typhimurium ΔcpxR Δlon Δasd secreting the B subunit of the Escherichia coli heat-labile enterotoxin were used as a live form of mucosal adjuvant for this study. Pregnant sows were divided into 4 groups of 3 sows apiece. Sows were primed at 8 weeks of pregnancy and were boosted 11 weeks of pregnancy. Group A sows were primed intramuscularly with the formalin-inactivated vaccine and boosted orally with the live vaccine and mucosal adjuvant, group B sows were orally primed with the live vaccine and mucosal adjuvant and boosted orally with live vaccine, group C sows were orally primed with live vaccine and mucosal adjuvant and intramuscularly boosted, and group D sows were primed and boosted with phosphate-buffered saline as controls. Piglets were orally challenged with a virulent S. Typhimurium strain at day 6 after birth. Sows from group A and B had significantly increased IgG levels compared to control group sows ( P < 0.05), and group C sows had lower IgG levels compared to group A and B sows. Mucosal sIgA and IgG levels in group A and B sow colostrums were significantly increased as compared to those of group D sows ( P < 0.05). Serum IgG and IgA levels in group A and B piglets were also significantly increased as compared to those of group D piglets ( P < 0.001). These data suggested that systemic and mucosal immune responses were highly induced by the vaccine candidate, especially when this was administered by both routes of intramuscular-prime and oral booster, and oral prime and booster. Furthermore, clinical signs such as diarrhea and weight loss were not observed after virulent Salmonella strain challenge in group A and B suckling piglets, however, group C (41.7%) and group D (83.3%) piglets suffered from diarrhea. This data suggested that sow immunized by intramuscular-prime and oral booster and oral prime and oral booster with this vaccine candidate effectively protected piglets from salmonellosis.

Humoral immune response of broilers fed diets containing yeast extract and prebiotics in the prestarter phase and raised at different temperatures

SUMMARY Feedstuffs and additives with immunomodulatory characteristics were investigated to reduce losses caused by disease and to optimize the production potential of the bird. Therefore, the objective of this study was to assess the influence of yeast extract and prebiotics on broilers fed a prestarter diet, and the impact of ambient temperature on maternal and postvaccinal humoral immune responses. The birds were fed diets supplemented with yeast extract, prebiotics, or both in the prestarter phase (1 to 7 d), and from d 8 on, all birds received the same diet. The birds were vaccinated against Newcastle disease virus and infectious bursal disease at 8 and 18 d of age. The addition of yeast extract and prebiotic in the prestarter phase did not change the humoral immune response against Newcastle disease virus or infectious bursal disease throughout the production cycle of the broilers. The higher temperature increased IgG levels, especially maternal antibody titers, despite the immunomodulating effect of heat stress until the second week of life.

Antioxidant, hepatoprotective and immuno-stimulant effects of nutraceutical compounds from carotenoid origin in rat treated with carbon tetrachloride

Aim of the work: the present study was conducted to evaluate antioxidant, hepatoprotective, and immuno-stimulant properties of carotenes derived from food byproducts (tomato peels (TPW), mango peels (MP), corn gluten (CG), and agriculture dill waste (DW)), they were selected for their high superoxide dismutase activity (SOD). Material and methods: antioxidant and hepatoprotective effects were investigated in carbon tetrachloride (CCl4) damaged liver. Rats treated with oral doses of each carotene (25 mg /Kg b.wt.) for 15 days prior CCl4 administration and 4 days post- CCl4-treatment. Results: all tested carotenes significantly reduced the elevated values of liver function tests (GGT, ALT & AST) in hepatic damaged groups as well as, they had an immuno-stimulate property. They increased IgG levels in normal and liver damaged rats treated with the tested carotenoids. Whereas, IgG level reduced significantly by CCl4-tereatment. Histopathological examination of the liver tissues exposed to CCl4 showed inflammatory cell infiltration, necrosis and fibrosis. Glycogen and total protein contents also recorded. Treatments with carotenoids led to an improvement in the histological and histochemical alterations induced by CCl4. Conclusion, carotenes may play an important role as nutraceutical preparation, specially, when obtained from wastes of food byproducts in which economically of low coast production.

Induction of opsonophagocytic killing activity with pneumococcal conjugate vaccine in human immunodeficiency virus-infected Ugandan adults

The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of non-functional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the levels of serotype-specific IgG in sera were determined. Significant increases were found in the OPK titers and IgG levels for both serotypes after CV vaccination irrespective of HIV status. Increases in IgG levels and OPK titers were largely dependent on the CD4 + cell counts, except for increases in the IgG levels for serotype 4. The proportions with serum OPK titer equal to or greater than 8 were 0–4.3% for serotype 4 and 26.7–42.9% for serotype 14 before vaccination, but the proportions increased up to 43.3–86.2% for serotype 4 and 63.3–96.6% for serotype 14 in all three groups 2 months after CV vaccination. The serum OPK titers remained at levels higher than the pre-vaccination level for at least 8 months after CV vaccination. A single dose of CV could afford some protective immunity in HIV-infected African adults before the introduction of antiretroviral therapy.

Enhanced levels of cow’s milk antibodies in infancy in children who develop type 1 diabetes later in childhood

Early exposure to cow's milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. We studied a subgroup of 94 children randomized to be weaned to a CM-based infant formula in the trial to reduce insulin-dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen-conferred T1D susceptibility and had an affected first-degree relative. After 7 years of follow-up, 8 subjects had progressed to T1D, 15 had at least one disease-associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta-lactoglobulin (BLG), bovine serum albumin, and alpha-casein and IgG antibodies to bovine insulin (BI) were measured with enzyme-linked immunosorbent assays from sequential samples. The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody-positive subjects than in autoantibody-negative subjects at 18 months of age (p = 0.022). An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D.

Diagnostic criteria for autoimmune hepatitis

Diagnosis of Autoimmune Hepatitis (AIH) often represents a clinical challenge. The clinical spectrum of disease is quite heterogeneous. AIH can affect patients of all age groups, both sexes, and any race and region. The course may range from subclinical and very mild to acute attacks of hepatitis up to fulminant hepatic failure. Other patients present very late with the picture of cryptogenic cirrhosis. Laboratory features may also differ. Autoantibodies vary, and some patients do not display any autoantibodies at the time of clinical presentation. SLA/LP-autoantibodies are the only antibodies specific for the diagnosis of AIH, but they are only present in about 20% of cases. The most common feature in all patients with AIH is an elevation of IgG levels, usually a selective or highly preferential elevation of IgG in comparison to IgA and IgM. However, in some patients the relative increase in IgG levels may be within the normal limits, because the normal range is quite wide. The diagnosis of AIH should not be made without a liver biopsy showing inflammatory hepatitis. Histology mayshow typical features such as enrichment of plasma cells and piecemeal necroses, but distinction from other inflammatory liver disease including allergic drug reactions may be difficult. The International Autoimmune Hepatitis Group has tried to define diagnostic criteria on the basis of consensus discussions. These were revised in 1999 in the light of some clinical studies. However, the criteria are complicated, and not useful in everyday practise. In addition, the criteria were only designed as a scientific tool in order to create comparable groups in publication from different centres. Therefore, the International Autoimmune Hepatitis Group has re-approached the problem with the aim of defining simplified criteria for everyday use. With the help of various specialised centres in the world we evaluated a number of hypothetical criteria, and found out, that four criteria with two categories are sufficient to either make or exclude the diagnosis of AIH with positive and negative predictive values well over 90%: 1 point2 points1. IgG>16 g/l>18 g/l2. ANA, SMA>1 : 40>1 : 80 or SLA/LP+3. Histologycompatible withtypical for AIH4. Viral markersnegativeA value of 6 or more points makes the diagnosis of AIH very likely, a value of 7 or 8 points demonstrates definite AIH. The simplified criteria should help in the diagnosis of AIH in patients with liver disease, and they seem to be valid world-wide. Prospective data are needed to validate these criteria further.

An Observational Study on Outgrowing Food Allergy during Non-Birch Pollen-Specific, Subcutaneous Immunotherapy

Background: Birch pollen-specific immunotherapy (SIT) decreases allergy to foods containing birch pollen-homologous allergens. Cross-reactivity was also observed between plane tree pollen and some vegetable foods. Objective: The aim of this study was to evaluate the outgrowing of food allergy by patients suffering from vegetable food allergy associated with plane tree pollinosis (rhinoconjunctivitis and/or asthma) during plane tree pollen SIT. Methods: An observational and prospective study was conducted in 16 adult patients suffering from vegetable food allergy (hazelnut, walnut, lettuce, peach and cherry) and from plane tree pollinosis receiving plane tree pollen SIT for 1 year. Open oral challenges with the implicated food were performed before and after SIT. Blood samples were drawn for measurement of pollen- and food-specific IgE and IgG4 before and after treatment. Results: Plane tree SIT resulted in a significant decrease in food allergy, since the mean food quantity provoking objective symptoms increased from 2.19 to 13.74 g (p < 0.05), and 6 of the 11 patients tolerated the highest level (25 g) of the challenged food after plane tree SIT. Laboratory data also showed a decrease in IgE levels and an increase in IgG4 levels after immunotherapy. Conclusion: SIT with plane tree pollen has a positive impact on food allergy in plane tree pollen-allergic subjects.

Neutralizing antibodies obtained in a persistent immune response are effective against deleterious effects induced by the Thalassophryne nattereri fish venom

Thalassophryne nattereri envenoming represents a great cost to North and Northeast Brazilian communities in terms of public healths, leisure and tourism. Victims rapidally develop symptoms as pain, local swelling, erythema followed by intense necrosis that persist for long days. The aim of this work was tested the immune competence of neutralizing antibodies in pre-immunized mice against principal toxic activities induced by venom. During the primary antibody response in mice, an elevation of IgG antibody levels was only observed on day 28. After boosting, high antibody levels were detected between days 49 and 70, with a 12-fold increase in IgG level over control values at day 49. We confirmed the in vitro neutralizing capacity of T. nattereri anti-venom against toxic effects and thereafter we show that neutralizing antibodies obtained in a persistent immune response are more effective, inclusive against edematous reaction. After boosting during the secondary response mice with high antibody levels do not present any alterations in venule or arteriole after topical application of venom on cremaster muscle. In addition, CK activity diminished in these mice with high neutralizing antibody levels corroborating the attenuation of the myonecrotic effect by venom. In addition, we determined the presence of high IgG antibodies levels in patients 6 months after injury by T. nattereri. In conclusion, the presence of neutralizing antibodies against to T. nattereri venom in the serum of pre-immunized mice could change the outcome of lesion at site of posterior envenoming. Antigen-specific antibodies of high affinity in consequence to specific immune response, dependent of T lymphocyte activation, could minimize the symptoms of intense and immediate inflammatory reaction caused by T. nattereri venom. These finding prompt us to the possibility of development of immune therapeutic strategies using specific anti-venom as an efficient intervention for protecting human victims.

Modulation of immune mediators with MQT-based immunotherapy

Assess immune and clinical changes with immunotherapy based on modified quantitative testing (MQT). Immunotherapy promotes immunomodulation that occurs over several years. Quantitative testing offers the advantage of initiating immunotherapy with robust antigen concentrations. This study assessed whether changes in immune mediators and allergy symptoms occur rapidly using quantitative techniques. Sixteen allergic adults were tested using MQT. Subjects had serum drawn for immunoglobulins E and G4 (IgE, IgG4) to 3 antigens, Der p1, Der f1, and Fel d1, and for interleukins IL-1beta, IL-2, IL-4, IL-5, IL-10, IL-12, and IL-13, and IL-1 receptor antagonist (IL-1RA). Subjects also completed the Sino-Nasal Outcome Test-20 (SNOT-20), the Allergy Outcome Scale (AOS), and the Rhinosinusitis Disability Index (RSDI). They underwent MQT-based immunotherapy and completed outcome measures again at 6 and 12 weeks. Nine subjects completed the study. Analysis demonstrated significant increases in IgG4 levels to all antigens, significant decreases in serum levels of IL-1beta and IL-5, and significant increases in levels of IL-1RA. Improvement was also noted in AOS and RSDI subscales. Immunotherapy based on MQT demonstrates significant changes in immunoglobulin and cytokine levels by 12 weeks following initiation. In addition, improvement in symptom and quality-of-life measures occurs by 12 weeks. These findings support the rapid onset of clinical effects with MQT-based treatment of inhalant allergy. C-4.