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IgG4
Kinds of IgG4 Terms modified by IgG4 Selected AbstractsHuman dendritic cells transfected with allergen-DNA stimulate specific immunoglobulin G4 but not specific immunoglobulin E production of autologous B cells from atopic individuals in vitroIMMUNOLOGY, Issue 2 2007Bettina König Summary Atopic/allergic diseases are characterized by T helper 2 (Th2)-dominated immune responses resulting in immunoglobulin E (IgE) production. DNA-based immunotherapies have been shown to shift the immune response towards Th1 in animal models. In further studies we showed that human dendritic cells (DC) transfected with allergen-DNA are able to stimulate autologous CD4+ T cells from atopic individuals to produce Th1 instead of Th2 cytokines and to activate interferon-, (IFN-,)-producing CD8+ T cells. The aim of this study was to analyse whether DC transfected with allergen-DNA are also able to influence immunoglobulin production of B cells from atopic donors. For this purpose, human monocyte-derived DC from grass-pollen allergic donors were transfected with an adenovirus encoding the allergen Phleum pratense 1 and cocultured with B cells, autologous CD4+ T cells, and CD40 ligand-transfected L-cells. B cells receiving help from CD4+ T cells stimulated with allergen-transfected dendritic cells produced more allergen-specific IgG4 compared to stimulation with allergen protein pulsed DC or medium, while total IgG4 production was not affected. In contrast, specific IgE production was not enhanced by stimulation with allergen-DNA transfected DC compared to medium and inhibited compared to allergen protein-pulsed DC with similar effects on total IgE production in vitro. Allergen-DNA transfected dendritic cells are able to direct the human allergic immune response from Th2-dominance towards Th1 and Tc1 also resulting in decreased IgE and increased IgG4 production. [source] Mechanisms of immune suppression by interleukin-10 and transforming growth factor-,: the role of T regulatory cellsIMMUNOLOGY, Issue 4 2006Alison Taylor Summary Specific immune suppression and induction of tolerance are essential processes in the regulation and circumvention of immune defence. The balance between allergen-specific type 1 regulatory (Tr1) cells and T helper (Th) 2 cells appears to be decisive in the development of allergy. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals. In contrast, there is a high frequency of allergen-specific interleukin-4 (IL-4)-secreting T cells in allergic individuals. Allergen-specific immunotherapy can induce specific Tr1 cells that abolish allergen-induced proliferation of Th1 and Th2 cells, as well as their cytokine production. Tr1 cells utilize multiple suppressor mechanisms, such as IL-10 and transforming growth factor-, (TGF-,) as secreted cytokines and various surface molecules, such as cytotoxic T-lymphocyte antigen 4 and programmed death-1. IL-10 only inhibits T cells stimulated by low numbers of triggered T-cell receptors, which depend on CD28 costimulation. IL-10 inhibits CD28 tyrosine phosphorylation, preventing the binding of phosphatidylinositol 3-kinase p85 and consequently inhibiting the CD28 signalling pathway. In addition, IL-10 and TGF-, secreted by Tr1 cells skew the antibody production from immunoglobulin E (IgE) towards the non-inflammatory isotypes IgG4 and IgA, respectively. Induction of antigen-specific Tr1 cells can thus re-direct an inappropriate immune response against allergens or auto-antigens using a broad range of suppressor mechanisms. [source] Hepatopancreatobiliary manifestations and complications associated with inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 9 2010Udayakumar Navaneethan MD Abstract Abstract: Diseases involving the hepatopancreatobiliary (HPB) system are frequently encountered in patients with inflammatory bowel disease (IBD). Hepatobiliary manifestations constitute some of the most common extraintestinal manifestations of IBD. They appear to occur with similar frequency in patients with Crohn's disease or ulcerative colitis. HPB manifestations may occur in following settings: 1) disease possibly associated with a shared pathogenetic mechanism with IBD including primary sclerosing cholangitis (PSC), small-duct PSC/pericholangitis and PSC/autoimmune hepatitis overlap, acute and chronic pancreatitis related to IBD; 2) diseases which parallel structural and physiological changes seen with IBD, including cholelithiasis, portal vein thrombosis, and hepatic abscess; and 3) diseases related to adverse effects associated with treatment of IBD, including drug-induced hepatitis, pancreatitis (purine-based agents), or liver cirrhosis (methotrexate), and reactivation of hepatitis B, and biologic agent-associated hepatosplenic lymphoma. Less common HPB manifestations that have been described in association with IBD include autoimmune pancreatitis (AIP), IgG4-associated cholangitis (IAC), primary biliary cirrhosis (PBC), fatty liver, granulomatous hepatitis, and amyloidosis. PSC is the most significant hepatobiliary manifestation associated with IBD and poses substantial challenges in management requiring a multidisciplinary approach. The natural disease course of PSC may progress to cirrhosis and ultimately require liver transplantation in spite of total proctocolectomy with ileal-pouch anal anastomosis. The association between AIP, IAC, and elevated serum IgG4 in patients with PSC is intriguing. The recently reported association between IAC and IBD may open the door to investigate these complex disorders. Further studies are warranted to help understand the pathogenesis of HPB manifestations associated with IBD, which would help clinicians better manage these patients. An interdisciplinary approach, involving gastroenterologists, hepatologists, and, in advanced cases, general, colorectal, and transplant surgeons is advocated. (Inflamm Bowel Dis 2010) [source] Affinity and catalytic heterogeneity of polyclonal myelin basic protein-hydrolyzing IgGs from sera of patients with multiple sclerosisJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 3 2010Galina A. Legostaeva Abstract Human myelin basic protein (hMBP)-hydrolyzing activity was recently shown to be an intrinsic property of antibodies (Abs) from multiple sclerosis (MS) patients. Here, we present the first evidence demonstrating a significant diversity of different fractions of polyclonal IgGs (pIgGs) from MS patients in their affinity for hMBP and in the ability of pIgGs to hydrolyze hBMP at different optimal pHs (3,10.5). IgGs containing ,- and ,-types of light chains demonstrated comparable relative activities in the hydrolysis of hMBP. IgGs of IgG1,IgG4 sub-classes were analyzed for catalytic activity. IgGs of all four sub-classes were catalytically active, with their contribution to the total activity of Abzs in the hydrolysis of hMBP and its 19-mer oligopeptide increasing in the order: IgG1 (1.5,2.1%) < IgG2 (4.9,12.8%) < IgG3 (14.7,25.0%) < IgG4 (71,78%). Our findings suggest that the immune systems of individual MS patients generate a variety of anti-hMBP abzymes with different catalytic properties, which can attack hMBP of myelin-proteolipid shell of axons, playing an important role in MS pathogenesis. [source] Characterization of a human monoclonal antibody obtained after immunization with plasma vaccine and a booster with recombinant-DNA hepatitis B vaccineJOURNAL OF MEDICAL VIROLOGY, Issue 3 2002R.A. Heijtink Abstract A human monoclonal antibody type IgG4, designated 1Ff4, was obtained by Epstein Barr virus transformation of peripheral blood lymphocytes from a hepatitis B vaccinee (HB-VAX: plasma-derived vaccine) after one boost of yeast recombinant DNA derived vaccine (Engerix-B). 1Ff4 binds preferentially to HBsAg/adw2 and HBsAg/ayw1. In binding experiments, it competes with antibodies induced by vaccination with HB-VAX-DNA (yeast recombinant) and HB-VAX (plasma-derived vaccine). 1Ff4 competes in part with a monoclonal antibody for the w/r region. Partial inhibition of binding of HBsAg/adw2 to solid phase anti-HBs was detected, resembling inhibition obtained using other human monoclonal specific for the "a"-loop. 1Ff4 does not bind to linear peptides covering the two "a"-loops or to an adw2/G145R mutant, its binding to wild type HBsAg strongly depends on the presence of disulphide bonds. In a large series of HBsAg-positive samples from an endemic area, 1Ff4 antibodies were successfully used to discriminate between an adw2 and an adrq+ strain. The characterisation of 1Ff4 and other human monoclonal anti-HBs antibodies may help to understand the fine specificity of protective antibodies elicited by immunization. J. Med. Virol. 66:304-311, 2002. © 2002 Wiley-Liss, Inc. [source] IgG4 as the predominant autoantibody in sera from patients with active state of pemphigus vulgarisJOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2004M Ayatollahi [source] Identification and characterization of IgG4-associated autoimmune hepatitisLIVER INTERNATIONAL, Issue 2 2010Hobyung Chung Abstract Background: Autoimmune hepatitis (AIH) and autoimmune pancreatitis (AIP) share clinical and pathological features such as high serum levels of immunoglobulin (Ig) G and autoantibodies, and lymphoplasmacytic infiltration, suggesting the presence of common immunological abnormalities. However, little is known about the possible involvement of IgG4, a hallmark of AIP, in AIH. Aims: In this study, we examined whether the IgG4 response contributes to the histopathological and clinical findings in AIH. Methods: Liver sections from 26 patients with AIH, 10 patients with primary biliary cirrhosis (PBC), three patients with primary sclerosing cholangitis (PSC) and 20 chronic hepatitis patients with hepatitis C virus (HCV) infection were immunostained for IgG4. We investigated the relationship among the histopathology, the responses to steroid therapy and the IgG4 staining. Results: Nine of the 26 liver specimens from patients with AIH showed positive staining for IgG4 whereas none of the 10 samples from patients with PBC, the three samples from patients with PSC or the 20 samples from patients with HCV hepatitis were positive. Patients with IgG4-positive AIH also showed increased serum levels of IgG. The numbers of T cells, B cells and plasma cells were significantly increased in the livers of patients with IgG4-positive AIH as compared with those patients with IgG4-negative AIH. Patients with IgG4-positive AIH also showed a marked response to prednisolone therapy. Conclusions: AIH may be classified into either an IgG4-associated type or an IgG4 non-associated type with the former showing a marked response to prednisolone treatment. [source] After 6 years with Xolair; a 3-year withdrawal follow-upALLERGY, Issue 1 2010A. Nopp Abstract Background:, This study reports the clinical and immunological state of patients 3 years after a 6-year period of Xolair treatment for severe allergic asthma. Methods:, The patient's cat allergen sensitivity, measured as CD-sens, IgE and IgE- and IgG4 antibodies, was analysed and compared with asthma severity evaluated from FEV1 and a questionnaire. Results:, Three years after treatment with Xolair was stopped, 12/18 patients reported improved or unchanged asthma compared with ongoing Xolair treatment. Most of the patients were in a stable clinical condition, 16/18 had not increased nightly asthma attacks and 14/18 little or no increase in medication. The CD-sens to cat was still significantly lower (P < 0.02) than untreated patients with allergic asthma and lower than expected from their serum IgE antibody levels. Conclusion:, Most of the patients in this study had, still 3 years after closing of 6 years Xolair treatment, a surprisingly mild and stable asthma. Interestingly, the observed, considerable, downregulation of basophil allergen sensitivity, CD-sens, most likely representing mast cell allergen sensitivity, contributed to the clinical results. [source] Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT studyALLERGY, Issue 9 2009H. Ott Background:, Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. Methods:, Patients (7.9,64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG4 measured. Results:, Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8,92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between ,11.3% and ,14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and ,1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG4 observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. Conclusions:, Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT. [source] Randomized double-blind, placebo-controlled trial of sublingual immunotherapy with a Pru p 3 quantified peach extractALLERGY, Issue 6 2009M. Fernández-Rivas Background:, Peach allergy is highly prevalent in the Mediterranean area; it is persistent and potentially severe, and therefore a prime target for immunotherapy. We aimed to study the efficacy and safety of sublingual immunotherapy (SLIT) with a peach extract quantified in mass units for Pru p 3, the peach lipid transfer protein. Methods:, Randomized, double-blind, placebo-controlled (DBPC) clinical trial. The main efficacy outcome was the change in the response to a DBPC food challenge (DBPCFC) with peach. Secondary efficacy outcomes were the changes in skin prick test (SPT), and in specific immunoglobulin E (IgE) and IgG4 to Pru p 3. Tolerance was assessed with a careful recording of adverse events. Results:, After 6 months of SLIT, the active group tolerated a significantly higher amount of peach (three- to ninefold), presented a significant decrease (5.3 times) in SPT, and a significant increase in IgE and IgG4 to Pru p 3. No significant changes were observed within the placebo group. Statistically significant inter-group differences were only observed in the SPT and IgG4 responses. No serious adverse events were reported. Systemic reactions were mild, and observed with a similar frequency in both groups. Local reactions were significantly more frequent in the active group (three times) and 95% of them restricted to the oral cavity. Conclusion:, In this first exploratory clinical trial, SLIT for peach allergy seems to be a promising therapeutic option that could modify the clinical reactivity of the patients to peach intake and the underlying immunological response with a good tolerance. [source] CD-sens: a biological measure of immunological changes stimulated by ASITALLERGY, Issue 5 2009A. Nopp Background:, Allergen-specific immunotherapy (ASIT) in allergic rhinitis and asthma is the only treatment that effects the long-term development of these diseases. Basophil allergen threshold sensitivity, CD-sens, which is a valuable complement to resource-demanding clinical challenge tests, was used to monitor the initiation of ASIT induced allergen ,blocking activity'. Methods:, Patients IgE-sensitized to timothy (n = 14) or birch (n = 19) pollen were started on conventional (8,16 weeks) or ultra rush ASIT, respectively, and followed by measurements of CD-sens, allergen binding activity (ABA) and serum IgG4- and IgE-antibody concentrations. Results:, CD-sens decreased during the early phase of ASIT-treatment. In parallel, ABA increased and correlated significantly with the increasing levels of IgG4 antibody concentrations. High dosages of allergen were more effective while mode of dosing up did not seem to matter. No change was seen in basophil reactivity. Conclusion:, CD-sens and ABA, in contrast to basophil reactivity, seem to be promising tools to monitor protective immune responses initiated by ASIT. [source] A specific mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides induces a beneficial immunoglobulin profile in infants at high risk for allergyALLERGY, Issue 3 2009E. Van Hoffen Background:, It has been suggested that human breast milk oligosaccharides play a role in the development of the immune system in infants, and may consequently inhibit the onset of allergy. A specific prebiotic mixture of short-chain galacto-oligosaccharides and long-chain fructo-oligosaccharides (GOS/FOS) has been shown to reduce the incidence of atopic dermatitis (AD) at 6 months of age in infants at risk for allergy. Aim of the study:, This study was aimed to analyze the effect of GOS/FOS on the immune response in these infants. Methods:, In a double-blind randomized placebo-controlled study, infants received a hypoallergenic whey formula with either 8 g/l GOS/FOS in a 9 : 1 ratio (IMMUNOFORTISTM) or 8 g/l maltodextrine (placebo) for 6 months. At 3 months of age, children were vaccinated with Hexavac against a.o. diphteria, tetanus, polio (DTP). At 6 months of age, plasma samples were collected from 84 infants (verum group n = 41, placebo group n = 43). Levels of total immunoglobulins (Ig) and of cow's milk protein (CMP-) and DTP-specific Ig were measured. Results:, GOS/FOS supplementation led to a significant reduction in the plasma level of total IgE, IgG1, IgG2 and IgG3, whereas no effect on IgG4 was observed. CMP-specific IgG1 was significantly decreased. DTP-specific Ig levels were not affected. Conclusions:, This study shows that GOS/FOS supplementation induces a beneficial antibody profile. GOS/FOS reduces the total Ig response and modulates the immune response towards CMP, while leaving the response to vaccination intact. This suggests that oral GOS/FOS supplementation is a safe method to restrain the atopic march. [source] Efficacy of grass pollen sublingual immunotherapy for three consecutive seasons and after cessation of treatment: the ECRIT studyALLERGY, Issue 1 2009H. Ott Background:, Data supporting a carry-over effect with sublingual immunotherapy (SLIT) are scarce. This randomized, double-blind, placebo-controlled study evaluated the efficacy, carry-over effect and safety of grass pollen SLIT using co-seasonal treatment. Methods:, Patients (7.9,64.7 years) with grass pollen allergy received ultra-rush titration with increasing doses (30, 90, 150 and 300 IR) of a 5-grass pollen mixture every 20 min at the start of the pollen seasons, followed by 300 IR daily until the end of the pollen seasons. A baseline season (no SLIT) was followed by three consecutive treatment seasons and one follow-up season. Symptoms, medication and adverse events were documented and specific immunoglobulin (Ig)E and IgG4 measured. Results:, Data were analysed for 183 of the 213 randomized patients. Mean treatment duration varied between seasons (81.8,92.7 days). Combined scores (symptoms and medication) improved progressively across treatment seasons (up to 44.7% improvement for SLIT compared with baseline) and fluctuated between ,11.3% and ,14.8% for placebo (P < 0.05). Similar changes were observed for symptom scores, with a successive decrease of 39.7% (SLIT) and fluctuations between +13.6% and ,1.51% for placebo (P < 0.05). Combined score (P = 0.0508) and symptom score improvements (P = 0.0144) with SLIT continued during follow up. Increases in specific IgG4 observed in the first season were sustained for SLIT vs placebo throughout treatment (P = 0.0001). Titration and daily SLIT were well tolerated. No serious systemic or anaphylactic reactions were reported. Conclusions:, Seasonal SLIT with ultra-rush titration is well tolerated and effective from the first treatment season onwards. These data indicate a carry-over effect of seasonal SLIT. [source] Testing for IgG4 against foods is not recommended as a diagnostic tool: EAACI Task Force Report,ALLERGY, Issue 7 2008Steven O. Stapel Serological tests for immunoglobulin G4 (IgG4) against foods are persistently promoted for the diagnosis of food-induced hypersensitivity. Since many patients believe that their symptoms are related to food ingestion without diagnostic confirmation of a causal relationship, tests for food-specific IgG4 represent a growing market. Testing for blood IgG4 against different foods is performed with large-scale screening for hundreds of food items by enzyme-linked immunosorbent assay-type and radioallergosorbent-type assays in young children, adolescents and adults. However, many serum samples show positive IgG4 results without corresponding clinical symptoms. These findings, combined with the lack of convincing evidence for histamine-releasing properties of IgG4 in humans, and lack of any controlled studies on the diagnostic value of IgG4 testing in food allergy, do not provide any basis for the hypothesis that food-specific IgG4 should be attributed with an effector role in food hypersensitivity. In contrast to the disputed beliefs, IgG4 against foods indicates that the organism has been repeatedly exposed to food components, recognized as foreign proteins by the immune system. Its presence should not be considered as a factor which induces hypersensitivity, but rather as an indicator for immunological tolerance, linked to the activity of regulatory T cells. In conclusion, food-specific IgG4 does not indicate (imminent) food allergy or intolerance, but rather a physiological response of the immune system after exposition to food components. Therefore, testing of IgG4 to foods is considered as irrelevant for the laboratory work-up of food allergy or intolerance and should not be performed in case of food-related complaints. [source] IgG4 -mediated allergic reaction to glargine insulinALLERGY, Issue 8 2006M. F. Madero No abstract is available for this article. [source] Salivary IgA and IgG subclasses in oral mucosal diseasesORAL DISEASES, Issue 6 2002S Sistig OBJECTIVE:,It was hypothesized that serum levels of immunoglobulins may play a role in the pathogenesis of oral mucosal diseases, or reflect clinical changes in these conditions, but little is known about the role of salivary immunoglobulins in the pathogenesis of these diseases. The aim of this study was to investigate possible alterations in salivary immunoglobulin A (IgA) and IgG subclasses in patients with oral mucosal inflammatory diseases. SUBJECTS and METHODS:,Levels of IgG1, IgG2, IgG3 and IgG4 were determined by enzyme-linked immunosorbent assay (ELISA), and IgA1 and IgA2 by radial immunodiffusion in the resting whole saliva of 31 patients with acute recurrent aphthous ulceration (RAU) (and followed in remission), 11 patients with chronic hyperplastic candidal infection (CHC), 12 patients with Sjögren's syndrome (SS), six patients with oral lichen planus (OLP), and 18 healthy volunteers using the normal saliva as a comparison point for all. RESULTS:,IgG and IgA subclasses were increased in OLP. In CHC all IgG subclasses were increased while IgA1 was decreased, IgG1, IgG3 and IgG4 levels were increased in SS, while all IgG subclasses as well as IgA2 were increased in acute RAU in comparison with healthy controls. No differences in any immunoglobulin subclasses between major and minor acute RAU were found. In remission, IgG1 and IgG4 returned to normal values while IgG2, IgG3, and IgA2 remained increased in patients with RAU. CONCLUSION:,Salivary immunoglobulin subclasses vary in different oral mucosal conditions and may play a role in oral mucosal inflammatory diseases and/or reflect clinical changes in these conditions. [source] Elevated levels of IgG3 and IgG4 subclass in paediatric cases of kala azarPARASITE IMMUNOLOGY, Issue 8 2008N. A. ANSARI SUMMARY Visceral leishmaniasis (VL) or Kala azar (KA) is a systemic disease caused by the parasites of the Leishmania donovani complex. Control measures rely on treatment with antileishmanial agents, however, fraught with problems such as toxicity or drug resistance. The incidence rate is on the rise for children, for reasons yet undefined. Previously we have shown significantly elevated level of IL-10 in children compared to adult KA cases. Here, antileishmanial antibody and C-reactive protein (CRP) levels were investigated in paediatrics and adult patients of KA and post-KA dermal leishmaniasis (PKDL). Level of IgG4 was significantly elevated in PKDL compared to KA, although total IgG and IgG1 were significantly lower. The antileishmania antibody levels of subclass IgG3 and IgG4 were found significantly elevated in paediatrics, however, levels of IgG, IgG1, IgG2 and CRP were comparable in paediatric and adult KA cases. In case of PKDL, levels of IgG and it subclass were similar in the two groups. No significant difference in antileishmanial antibody level was noticed between macular or polymorphic cases of PKDL. The differential antibody intensity in paediatric cases, together with significant level of circulating IL-10, could be considered as a marker of differential disease susceptibility. [source] Analysis of specific IgE and IgG subclass antibodies for diagnosis of Echinococcus granulosusPARASITE IMMUNOLOGY, Issue 8 2006A. R. KHABIRI SUMMARY The potential roles of specific antibodies of different immunoglobulin G (IgG) subclasses and IgE in serological diagnosis of cystic echinococcosis (CE) were investigated by an enzyme linked immunosorbent assay (ELISA) based on Antigen 5 (Ag5). Presence of IgG1 was demonstrated in all sera from 58 patients with CE. The most discriminatory and specific antibodies found in this study belonged to IgG4 and IgE. Only one false-positive reaction was observed with IgG4 and no IgE cross-reactivity occurred with 40 sera from healthy controls. In 36 sera from patients infected with parasites other than CE two false-positive reactions with IgG4 were observed but none occurred with IgE. In immunoblotting, it was shown that IgG1 subclass was responsible for cross-reactivity of human antibodies that reacted with a 38 kDa subunit of Ag5. IgG4 and IgE antibodies could not recognize the 38 kDa subunit and under non-reducing conditions reacted with the 57 kDa subunit without any cross-reactivity to other parasites. The results demonstrated that IgG4 and IgE are the most important antibodies for serological diagnosis of hydatid cyst in an Ag5 based immunoassay system. [source] Comparison of an enzyme linked immunosorbent assay (ELISA) and a radioallergosorbent test (RAST) for detection of IgE antibodies to Brugia malayiPARASITE IMMUNOLOGY, Issue 11-12 2003Sitti Wahyuni SUMMARY The enzyme linked immunosorbent assay (ELISA) for specific IgE antibodies to Brugia malayi was compared with the radioallergosorbent test (RAST) for use in immunoepidemiological studies of lymphatic filariasis. Sera used were from individuals (aged 5,82 years) living in an area endemic for lymphatic filariasis in South Sulawesi, Indonesia. The percentage of positive IgE ELISA reactions (52·6%) among the population was lower than the percentage of positive RAST (94·5%). Although an overall significant concordance was found between the two assays (P < 0·001), 328 (42·7%) individuals with a positive RAST result were negative in the ELISA, whereas only 6 (0·8%) subjects were positive by ELISA, yet negative by RAST. When the population was divided into those with active infection (positive for anti-filarial IgG4) and those not infected (mf-negative and negative for anti-filarial IgG4), the correlation between the two tests was higher in the IgG4-positive (rho = 0·70) than in the IgG4-negative (rho = 0·52) group. These results indicate that in assessment of B. malayi specific IgE antibody, RAST is superior to ELISA. However, given the use of radioactivity in the RAST method and given our results obtained in subjects with high anti-filarial IgG4, one could consider using the IgE-ELISA in areas with high endemicity for filariasis. In areas with low endemicity or where control programs are implemented, sera will have to be tested by RAST. [source] Molecular and immunological characterization of the C-terminal region of a new Echinococcus granulosus Heat Shock Protein 70PARASITE IMMUNOLOGY, Issue 3 2003E. Ortona SUMMARY By screening an expression library of Echinococcus granulosus with IgE from sera of patients with cystic echinococcosis (CE) and allergic reactions, we isolated the C-terminal region of a new heat shock protein (HSP)70 of E. granulosus. The protein, named Eg2HSP70, has close homology with the C-terminal region of Dermatophagoides farinae and human HSP70. We investigated the humoral and cell-mediated immune responses to this antigen in patients with CE grouped according to the presence of allergic reactions. Immunoblotting detected total IgG, IgG4 and IgE specific to Eg2HSP70 (83% of sera contained IgG, 31% IgG4 and 57% IgE). No significant difference was found in immunoglobulin percentages according to the presence of allergic reactions. Immunoblotting inhibition showed that no IgG or IgE specific to Eg2HSP70 cross-reacted with D. farinae or human HSP70. Eg2HSP70-stimulated PBMC from 26 patients produced significantly greater amounts of TNF-,, IFN-,, and IL-10 than unstimulated cultures in all patients, irrespective of the presence of allergic reactions (P < 0·05). They also produced significantly greater amounts of IL-4 than unstimulated cultures exclusively in patients with allergic reactions (P < 0·05). These findings show that Eg2HSP70 is a new antigenic molecule inducing both B and T cell responses. [source] Cellular responses and cytokine profiles in Ascaris lumbricoides and Trichuris trichiura infected patientsPARASITE IMMUNOLOGY, Issue 11-12 2002Stefan M. Geiger SUMMARY The impact of intestinal helminth infection, i.e. Ascaris lumbricoides and Trichuris trichiura, on cellular responsiveness and cytokine production was investigated in young adults. Ascaris -specific cellular responsiveness was higher in parasite-free endemic controls than in patients infected with T. trichiura, or A. lumbricoides, or patients co-infected with both parasites. Also, mitogen-induced tumour necrosis factor (TNF)-,, interleukin (IL)-12 and interferon (IFN)-, secretion by peripheral blood mononuclear cells (PBMC) was higher in negative endemic controls than in infected individuals. Ascaris antigen-specific production of TNF-,, IL-12 and IFN-, was low in singly Ascaris as well as in co-infected patients, whereas secretion of IL-10 and IL-13 was elevated and similarly high in all patient groups. The detection of Trichuris -specific and Ascaris -specific IgG4 revealed significantly higher serum antibody levels in Trichuris or Ascaris patients when compared to endemic controls (P < 0·05), whereas parasite-specific IgE antibody levels were similarly high in infected individuals and in endemic controls. In summary, chronically infected Ascaris and Trichuris patients with a high parasite load presented reduced cellular reactivity and lower type 1 TNF-,, IFN-, and IL-12 responses when compared with endemic controls, whereas type 2 IL-10 and IL-13 productions were similar in all groups from the endemic area. The former may support parasite persistence, whereas substantial type 2 cytokine release may promote protective immunity, suggesting an adaptation of the host to control the parasite burden while minimizing immune-mediated host self-damage. [source] Ocular adnexal IgG4-related disease has uniform clinicopathologyPATHOLOGY INTERNATIONAL, Issue 8 2008Yasuharu Sato IgG4-related disease is a recently proposed clinical entity with several unique clinicopathological features. Ocular adnexal IgG4-related disease, however, has not well been clarified. The purpose of the present study was to examine 21 patients (10 men, 11 women; age range, 39,86 years) with ocular adnexal IgG4-related disease. In 17 out of 21 patients (81%), the lacrimal glands were involved and bilateral lacrimal gland swelling was frequently observed (n = 12; 70.6%). In contrast, the conjunctiva was not involved in any of the patient. Histology was uniform with marked lymphoplasmacytic infiltration admixed with dense fibrosis, similar to previous reports of IgG4-related disease. Immunostaining detected numerous aggregates of IgG4-positive plasma cells. Serum IgG4 was higher than normal in 10 of the 13 patients tested, although it was measured after treatment in almost all cases. Interestingly, immunoglobulin heavy chain gene rearrangement was detected in two of 17 patients (12%) examined. The present results show that ocular adnexal IgG4-related disease has uniform clinicopathology: that is, disease involving the bilateral lacrimal glands with lymphoid hyperplasia and fibrosis, but not the conjunctiva. And presence of immunoglobulin heavy chain gene rearrangement suggests the possibility of B-cell lymphoma arising in a background of IgG4-related chronic inflammation. [source] The clinical significance of food specific IgE/IgG4 in food specific atopic dermatitisPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2007Geunwoong Noh Food is closely associated with the pathogenesis of atopic dermatitis. Food allergy is usually mediated by IgE antibody to specific food proteins and determination of specific IgE antibody is the basis of the common diagnostic test for food allergy. IgG4 have been reported as blocking antibody and the protective effects of blocking antibody may be clear in inhalant allergy. However, the role of IgG4 in food allergy is still a matter of debate. In this study, the clinical significance of food allergen-specific IgE/IgG4 in atopic dermatitis was investigated and compared with that of IgE. A total of 97 patients who fulfilled the diagnostic criteria for atopic dermatitis participated in this study. Skin prick test and allergy patch test were performed. Specific IgE and IgG4 concentration were measured using allergy protein chip, ,AllergyChip'. Double blinded placebo controlled food challenge test (DBPCFC) was performed for the diagnosis of allergy to milk, egg white, wheat, and soybean. DBPCFCs for milk, egg white, soybean, and wheat were performed. The positive rates were 31.7% (19/60) in milk, 36.7% (18/49) in egg white, 30.4% (7/23) in soybean, and 34.8% (8/23) in wheat. Mean IgE/IgG4 levels in DBPCFC (+) subjects is higher than those in DBPCFC (,) subjects in all food items studied. Of them, there were significantly different between two groups in egg white and wheat (Egg white in DBPCFC (+) vs. (,): 0.4 ± 0.3 vs. 0.2 ± 0.2, wheat in DBPCFC (+) vs. (,): 1.2 ± 1.2 vs. 0.3 ± 0.3, p < 0.05). Allergen-specific IgE/IgG4 may provide one of the clues to understand the mechanism of food allergy in atopic dermatitis. The present study suggests that protein microarray can be one of the useful methods to assess ongoing status of allergic diseases. [source] Casein-specific immunoglobulins in cow's milk allergic patient subgroups reveal a shift to IgA dominance in tolerant patientsPEDIATRIC ALLERGY AND IMMUNOLOGY, Issue 1 2007Gaynour B. G. Sletten Differences in casein-specific immunoglobulin (Ig) G-subclass and IgA serum levels between reactive and tolerant patients may hint at the immunopathogenesis during tolerance development in cow's milk allergy (CMA). , -, ,- and , -casein-specific IgG1, IgG4, IgE and IgA serum levels were compared in clinically reactive and tolerized IgE-mediated (n = 15) and non-IgE-mediated (n = 14) CMA with delayed gastrointestinal symptoms, using enzyme-linked immunosorbent assay (ELISA) and immunoblot techniques. The median anti-casein IgE levels in clinically reactive IgE-mediated CMA patients (n = 9) were 140- to 180-fold higher than in tolerized patients (n = 6) and 160- to 200-fold higher than in controls (n = 10). Median , -, ,- and , -casein-specific IgG1 and IgG4 levels were nine- to 60-fold higher in reactive patients and five- to 60-fold in tolerized patients. Clinical tolerance in IgE-mediated CMA was thus associated with decreased casein-specific IgE, IgG4 and IgG1, whereas serum IgA anti- , -, , - and , -casein remained practically unaltered. Tolerized cow's milk protein (CMP)-sensitive atopic dermatitis had, in particular, decreased , -casein-specific IgG1 levels, compared with clinically reactive patients. The ELISA levels to immunoblot correlation profile for the , -, , - and , -casein-specific IgE suggested that the IgE-mediated CMA patients predominantly reacted to tertiary , - and , -casein epitopes whereas the IgE in non-IgE-mediated patients reacted to linearized , -, , - and , -casein epitopes. Clinical tolerance in non-IgE-mediated CMA patients (n = 9) was associated with a four- to 10-fold decrease in casein-specific IgE levels, accompanied by a five- to eightfold decrease in IgG1 and five- to 60-fold decrease in IgG4 levels, whereas casein-specific IgA levels remained unaltered. Thus, tolerance in both patient groups was characterized by a generalized decreased humoral immune response to caseins, which induced a functional shift to IgA dominance. [source] Immunoglobulin subgroups in children with febrile seizuresPEDIATRICS INTERNATIONAL, Issue 1 2001Hüsey, n Çaksen Background: The aim of the present study was to determine whether or not there was a role for immunoglobulin (Ig) or IgG subgroups in the pathogenesis of febrile seizures (FS). Methods: Serum levels of IgA, total IgG, IgM, IgE, IgG1, IgG2, IgG3 and IgG4 were measured in 34 children with FS and in 37 healthy children used as a control group. Both patients and controls were divided into two groups according to age (group I, 6,24 months; group II, 25,72 months). Results: Compared with controls, mean IgG4 levels in patients were found to be decreased in both groups I and II (group I: 95~14 vs 57~5, respectively, P=0.01; group II: 178.5~38.5 vs 65.1~24.5, respectively, P<0.01), while mean IgG2 levels were found to be decreased only in group II patients (170~16 vs 103~22; P<0.05). Conclusions: The results of the present study suggest that Ig subclass deficiencies may be responsible for the infections connected with FS or that they may be related to the pathogenesis of FS in some children. [source] Placental transfer of IgG subclasses in a Japanese populationPEDIATRICS INTERNATIONAL, Issue 4 2000Shintaro Hashira Abstract Background: Maternal immunoglobulin G (IgG), transferred across the placenta to the fetus during intrauterine life, is an important component of the neonatal immunological defence mechanisms against infection. There is controversy with respect to differences in placental transfer of the different IgG subclasses, and no definite data are available on a Japanese population. Therefore, we investigated placental transfer of IgG subclasses in a Japanese population. Methods: A total of 228 matched pairs of cord and maternal serum samples (20,42 weeks gestation) were assayed for each IgG subclass by an enzyme-linked immunosorbent assay. Results: The mean values and hierarchy of cord/maternal concentration ratios of IgG subclasses at 40 weeks gestation were as follows: IgGl(1.47)>IgG3(1.17)=IgG4(1.15)>IgG2(0.80). The cord/maternal concentration ratios of all IgG subclasses were positively correlated to gestational age. The mean ratios for IgG1 and IgG4 nearly reached a plateau at 39 and 37 weeks gestation, respectively, while those for IgG2 and IgG3 increased until 41 weeks gestation. The ratios of all IgG subclasses for full-term deliveries were reciprocally correlated to the respective maternal IgG subclass serum levels. Conclusions: The results suggest that although all four IgG subclasses are actively transferred across the placenta, the efficiency of their transfer ranks in the order IgGl >IgG3=IgG4>IgG2. The different results as to placental transfer of IgG subclasses in the literature might be due, at least in part, to different maternal IgG subclass serum levels in the populations studied. [source] IGG4-RELATED SCLEROSING LYMPHOPLASMACYTIC PANCREATITIS AND CHOLANGITIS MIMICKING CARCINOMA OF PANCREAS AND KLATSKIN TUMOURANZ JOURNAL OF SURGERY, Issue 4 2008Moon-Tong Cheung Background: Autoimmune sclerosing pancreatitis is a well-known disease entity for years, particularly recognizing the difficulty in distinguishing it from malignancy. Immunohistochemical study showed that immunoglobulin IgG4 staining was positive in plasma cells of some autoimmune pancreatitis or cholangitis. The term ,autoimmune sclerosing pancreatocholangitis' was used as it was believed that they belonged to a range of disease involving both pancreas and biliary tree. It may also be part of a systemic fibro-inflammatory disease. Patients and Methods: All the patients suffering from immunoglobulin G4 (IgG4)-related pancreatitis and cholangitis from May 2003 to September 2006 in Queen Elizabeth Hospital, Hong Kong were retrospectively studied. Results: A total of five patients with clinical diagnosis of IgG4-related autoimmune pancreatitis or cholangitis were analysed. All presented with jaundice or abdominal pain, mimicking carcinoma. Two patients had major resection, two patients were diagnosed by intraoperative biopsy and one was based on serum IgG4 level. Conclusion: With the growing awareness of this relatively recently characterized clinical entity and its similar presentation to pancreatic carcinoma or bile duct cholangiocarcinoma, it is important for autoimmune sclerosing pancreatocholangitis to be included in the differential diagnosis of pancreaticobiliary disease. The management strategy has shown to be modified , from major resection to intraoperative biopsy and to the assay of serum IgG4 level without the necessity of histology confirmation. [source] Age- and sex-related differences in antibody responses against Schistosoma mansoni soluble egg antigen in a cohort of school children in Ethiopia,APMIS, Issue 12 2001F. ABEBE Acquired immunity is believed to be the main factor in the age-related differences in prevalence and intensity of Schistosoma infections. We studied antibody responses against S. mansoni soluble egg antigen (SEA) by ELISA in children before treatment, 5 weeks and one year after treatment. After screening for S. mansoni infection, positive children were treated with praziquantel (40 mg per kg body weight). Infection rate was significantly higher in boys younger than 12 years than in girls in the same age group. Levels of all antibody isotypes, except IgG1 (before treatment) or IgA (one year after treatment), were higher in children older or equal to 12 years than in those younger. The difference between age groups was significant for IgE, IgM, IgG3 and IgG4 (before treatment) and IgE (one year after treatment). Similarly, all antibody isotypes, except IgE, before treatment were higher in boys than in girls. At 5 weeks after treatment, IgG, IgE and IgG1 showed an increasing tendency, whereas IgM and IgG3 tended to decrease. One year after treatment, significant decreases were observed in IgG, IgG1 and IgG4 and a significant increase in IgG2 levels. The study presents further evidence for the difference in acquired immunity between younger and older children, and between boys and girls. The study also suggests that praziquantel differentially affects antibody responses against S. mansoni SEA. [source] Rituximab therapy leads to rapid decline of serum IgG4 levels and prompt clinical improvement in IgG4-related systemic diseaseARTHRITIS & RHEUMATISM, Issue 6 2010Arezou Khosroshahi Objective Patients with IgG4-related systemic disease (IgG4-RSD) frequently show an incomplete response to treatment with glucocorticoids and traditional disease-modifying antirheumatic drugs (DMARDs). B lymphocyte depletion is a therapeutic strategy known to be effective for pemphigus vulgaris, an autoimmune condition mediated by IgG4 autoantibodies. This study was performed to assess the clinical and serologic responses to B lymphocyte depletion therapy with rituximab in patients with IgG4-RSD. Methods Four patients with IgG4-RSD were treated with 2 intravenous doses (1 gram each) of rituximab. Clinical improvement was assessed by monitoring the tapering/discontinuation of prednisone and DMARDs, and by measuring the serum concentrations of B lymphocytes, immunoglobulins, and IgG subclasses before and after therapy. Results Clinical features of IgG4-RSD in these 4 patients included autoimmune pancreatitis, sclerosing cholangitis, lymphoplasmacytic aortitis, salivary gland involvement, orbital pseudotumor, and lacrimal gland enlargement. The 3 patients with elevated serum IgG and IgG4 levels at baseline had a mean IgG concentration of 2,003 mg/dl (normal range 600,1,500 mg/dl) and a mean IgG4 concentration of 2,160 mg/dl (normal range 8,140 mg/dl). Among these patients, the serum IgG4 concentrations declined by a mean of 65% within 2 months of rituximab administration. All 4 patients demonstrated striking clinical improvement within 1 month of the initiation of rituximab therapy, and tapering or discontinuation of their treatment with prednisone and DMARDs was achieved in all 4 patients. A decrease in IgG concentration was observed for the IgG4 subclass only. Conclusion Treatment with rituximab led to prompt clinical and serologic improvement in these patients with refractory IgG4-RSD, and is a viable treatment option for this condition. The decline in serum IgG4 concentrations was substantially steeper than that of the autoantibody concentrations in immune-mediated conditions in which rituximab is effective, such as in rheumatoid arthritis. In addition, the reduction in IgG-subclass levels appeared to be specific for IgG4. The swift improvement of IgG4-RSD suggests that rituximab achieves its effects in IgG4-RSD by depleting the pool of B lymphocytes that replenish short-lived IgG4-secreting plasma cells. [source] IgG4-related systemic disease and lymphoplasmacytic aortitisARTHRITIS & RHEUMATISM, Issue 10 2009John H. Stone We describe herein a patient who developed a dissection of the ascending aorta in the setting of IgG4-related systemic disease, linking IgG4-related systemic disease with a newly-recognized subset of noninfectious aortitis. At the time of aortic surgery, a transmural lymphoplasmacytic infiltrate was detected in the patient's aorta, with a principal focus of inflammation within the media. Immunohistochemical studies demonstrated that >50% of the plasma cells in the lesion stained for IgG4. By in situ hybridization, the plasma cells showed polytypic staining for kappa and lambda light chains, consistent with a polyclonal plasma cell infiltrate. Serologic evaluation revealed that the patient's IgG4 levels were elevated nearly 10-fold. Four years before aortic surgery, the patient had undergone a mediastinal lymph node biopsy. Reexamination of the lymph node revealed features consistent with IgG4-related systemic disease, which had not been recognized at the time of the original biopsy. Glucocorticoid therapy for the IgG4-related systemic disease yielded a prompt response. Recognition that IgG4-related systemic disease can involve the ascending as well as the descending abdominal aorta indicates the need for a change in the way idiopathic aortitis is regarded. This case offers new potential considerations for short- and long-term management of noninfectious aortitis, because of the frequent good response of IgG4-related systemic disease to glucocorticoid treatment without additional therapy. Treatment of the aortitis may prevent progression of the IgG4-related systemic disease to involvement of other organs. IgG4-related systemic disease should be considered in all patients with aortitis judged to be of unknown etiology. [source] | ||||||||||||||||||||||||||||