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Type I interferons (IFNs) are essential for antiviral immunity, appear to represent a key component of mRNA vaccine-adjuvanticity, and correlate with severity of systemic autoimmune disease. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-g induces T-bet expression and IgG2c isotype switching in B cells prior to this bifurcation and has no evident effects once GCs and bona fide Tfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c+ GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1+ GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through divergent Th1 and Tfh cell-dependent pathways. [ABSTRACT FROM AUTHOR]

Type I interferons (IFNs) are essential for antiviral immunity, appear to represent a key component of mRNA vaccine-adjuvanticity, and correlate with severity of systemic autoimmune disease. Relevant to all, type I IFNs can enhance germinal center (GC) B cell responses but underlying signaling pathways are incompletely understood. Here, we demonstrate that a succinct type I IFN response promotes GC formation and associated IgG subclass distribution primarily through signaling in cDCs and B cells. Type I IFN signaling in cDCs, distinct from cDC1, stimulates development of separable Tfh and Th1 cell subsets. However, Th cell-derived IFN-γ induces T-bet expression and IgG2c isotype switching in B cells prior to this bifurcation and has no evident effects once GCs and bona fide Tfh cells developed. This pathway acts in synergy with early B cell-intrinsic type I IFN signaling, which reinforces T-bet expression in B cells and leads to a selective amplification of the IgG2c+ GC B cell response. Despite the strong Th1 polarizing effect of type I IFNs, the Tfh cell subset develops into IL-4 producing cells that control the overall magnitude of the GCs and promote generation of IgG1+ GC B cells. Thus, type I IFNs act on B cells and cDCs to drive GC formation and to coordinate IgG subclass distribution through divergent Th1 and Tfh cell-dependent pathways.

After the outbreak of COVID-19, billions of vaccines with different types have been administrated, including recombinant protein vaccines and mRNA vaccines. Although both types of SARS-CoV-2 vaccine can protect people from viral infection, their differences in humoral and cellular immune responses are still not clearly understood. In this study, we made a head-to-head comparison between an mRNA vaccine candidate and a recombinant protein vaccine we developed previously. Results demonstrated that both vaccine candidates could elicit high specific binding and neutralizing antibody titers in BALB/c mice, but with bias towards different IgG subtypes. Besides, the mRNA vaccine candidate induces higher cellular immune responses than the recombinant protein vaccine. To date, this is the first reported study to directly compare the immune responses of both arms between SARS-CoV-2 mRNA and recombinant vaccines. [ABSTRACT FROM AUTHOR]

After the outbreak of COVID-19, billions of vaccines with different types have been administrated, including recombinant protein vaccines and mRNA vaccines. Although both types of SARS-CoV-2 vaccine can protect people from viral infection, their differences in humoral and cellular immune responses are still not clearly understood. In this study, we made a head-to-head comparison between an mRNA vaccine candidate and a recombinant protein vaccine we developed previously. Results demonstrated that both vaccine candidates could elicit high specific binding and neutralizing antibody titers in BALB/c mice, but with bias towards different IgG subtypes. Besides, the mRNA vaccine candidate induces higher cellular immune responses than the recombinant protein vaccine. To date, this is the first reported study to directly compare the immune responses of both arms between SARS-CoV-2 mRNA and recombinant vaccines.

Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response. Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at two time points during high malaria transmission and two time points following a dramatic reduction in transmission. Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age. Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG.

Understanding how immunity to malaria is affected by declining transmission is important to aid vaccine design and understand disease resurgence. Both IgG subclasses and avidity of antigen-specific responses are important components of an effective immune response. Using a multiplex bead array assay, we measured the total IgG, IgG subclasses, and avidity profiles of responses to 18 P. falciparum blood stage antigens in samples from 160 Ugandans collected at two time points during high malaria transmission and two time points following a dramatic reduction in transmission. Results demonstrated that, for the antigens tested, (i) the rate of decay of total IgG following infection declined with age and was driven consistently by the decrease in IgG3 and occasionally the decrease in IgG1; (ii) the proportion of IgG3 relative to IgG1 in the absence of infection increased with age; (iii) the increase in avidity index (the strength of association between the antibody and antigen) following infection was largely due to a rapid loss of non-avid compared to avid total IgG; and (iv) both avid and non-avid total IgG in the absence of infection increased with age. Further studies are required to understand the functional differences between IgG1 and IgG3 in order to determine their contribution to the longevity of protective immunity to malaria. Measuring changes in antibody avidity may be a better approach of detecting affinity maturation compared to avidity index due to the differential expansion and contraction of high and low avidity total IgG. [ABSTRACT FROM AUTHOR]

Introduction Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better understand differences in vaccine induced immunity, we determined pertussis, diphtheria, and tetanus (DTaP) vaccine antigen-specific IgG subclass responses in wP- and aP-primed children before and after two successive DTaP booster vaccinations. Methods Blood samples were collected in a cross-sectional study from wP- or aP-primed children before and 1 month after the pre-school DTaP booster vaccination at age 4 years. Blood samples were collected from two different wP- and aP-primed groups of children before, 1 month and 1 year after an additional pre-adolescent Tdap booster at age 9 years. IgG subclass levels against the antigens included in the DTaP vaccine have been determined with fluorescent-bead-based multiplex immunoassays. Results At 4 years of age, the IgG4 proportion and concentration for pertussis, diphtheria and tetanus vaccine antigens were significantly higher in aP-primed children compared with wP-primed children. IgG4 concentrations further increased upon the two successive booster vaccinations at 4 and 9 years of age in both wP- and aP-primed children, but remained significantly higher in aP-primed children. Conclusions The pertussis vaccinations administered in the primary series at infancy determine the vaccine antigen-specific IgG subclass profiles, not only against the pertussis vaccine antigens, but also against the co-administered diphtheria and tetanus vaccine antigens. These profiles did not change after DTaP booster vaccinations later in childhood. The different immune response with high proportions of specific IgG4 in some aP-primed children may contribute to a reduced protection against pertussis. ISRCTN65428640; ISRCTN64117538; NTR4089. [ABSTRACT FROM AUTHOR]

We conducted a retrospective study to evaluate the usefulness of immunoglobulin G (IgG) subclasses against Candida cell wall fragments (CW) and phosphopeptidomannan (PPM) for the diagnosis of invasive candidiasis (IC). We analyzed 54 patients with IC (n = 19), Candida heavy colonization (HC; n = 16), and controls (no IC or HC, n = 19). In nonneutropenic patients (n = 47), the sensitivity and specificity values of IgG1 anti-CW and IgG2 anti-PPM in IC were 88%, 59%, and 88%, 94%, respectively. The areas under the receiver operating characteristic curves were 0.69 (0.51-0.88) and 0.901 (0.78-1.02), respectively. IgG1 mean values (arbitrary units) and 95% confidence interval were 46 (20-71), 42 (-0.38 to 84) and 20 (8.3-32) in IC, HC, and in controls, respectively, and discriminated IC but not HC from controls (P = .032, and P = .77, respectively). IgG2 mean values were 26 (9.2-42), 19 (4.4-33), and 3.2 (0.28-6.6) in IC, HC, and in controls, respectively, and discriminated both IC and HC from controls (P < .0001 and P = .035, respectively) but did not separate IC from HC (P = .2). IgG2 showed positivity as early as one day after the IC diagnosis. Antibodies were detected in only two out of a total of seven neutropenic patients. For both IC and HC patients, the diagnostic performance of IgG2 anti-PPMwas better than the one of IgG1 anti-CW. In nonneutropenic patients, IgG2 anti-PPM accurately identified not only IC patients but also HC patients at high risk for IC. Thismarkermay help clinicians in the initiation of early preemptive therapy. [ABSTRACT FROM AUTHOR]

Abstract: Infection with human cytomegalovirus (HCMV), a ubiquitously distributed herpesvirus, has been associated with human immune system aging. Especially total HCMV specific IgG antibody (AB) titres have been correlated with human frailty and mortality. The aim of this study was to further assess to which extent HCMV specific subclass AB titres differ between individuals and whether this is associated with age and gender. ELISA tests detecting HCMV specific IgG subclass 1 and 3 ABs, the main subclass ABs directed against HCMV, were developed. Using these ELISAs, 145 (73 female and 72 male) age-matched patients, aged 17 to 87years, were tested. The results showed that the IgG1 and 3 subclass distribution was highly variable among individuals, and that female persons had significantly higher IgG3 titres than age-matched male persons (p=0.0073). A correlation of the IgG3 subclass titres with age was found in female persons (Spearman r=0.305, p=0.0088). Thus the total HCMV specific IgG level appears to consist of a variable and gender associated distribution of IgG subclass ABs developed against persistent HCMV infection. The analysis of IgG subclass titres therefore could further be used to refine previously established clinical associations of aging with total HCMV specific IgG AB titres. [Copyright &y& Elsevier]

Abstract: A major problem in the serodiagnosis of human toxocariasis in tropical countries is cross-reaction with antibodies to other helminthic diseases and a lack of sensitivity. The majority of tests currently available use total IgG and, in this study, the use of peroxidase-conjugated anti-human IgG subclass antibodies (IgG1-4) was compared with total IgG for the diagnosis of human toxocariasis by using Toxocara excretory–secretory (TES) antigens in an enzyme-linked immunosorbent assay (ELISA) format. All four IgG subclass antibodies gave approximately 10-fold increases in optical density (OD) values for 50 toxocariasis patients compared to 29 healthy normals; this was significantly greater than the approximate doubling of OD values seen in the total IgG-ELISA format. IgG2 gave by far the greatest sensitivity (values: IgG, 50%; IgG1, 60%; IgG2, 98%; IgG3, 78%; IgG4, 64%). Significant cross-reactivity using all IgG subclasses in the TES ELISA was seen with 141 serum samples from patients with 10 other helminthic infections. However, IgG3 gave the best specificity (values: IgG, 73%; IgG1, 76%; IgG2, 71%; IgG3, 81%; IgG4, 71%). Thus, of the IgG subclass antibodies, IgG2 appeared best and employing this subclass can improve the serodiagnosis of human toxocariasis since it recognises carbohydrate epitopes of TES antigens. [Copyright &y& Elsevier]

Epidemiological evidence has led to the hypothesis that the concurrent and predominant transmission of Onchocerca ochengi by Simulium damnosum s.l. in sub-Saharan Africa could lead to the protection of humans against onchocerciasis caused by Onchocerca volvulus (zooprophylaxis). To gain support for this hypothesis, we investigated whether exposure to O. volvulus could protect cattle from O. ochengi . Gudali calves were vaccinated with live O. volvulus -infective larvae and subsequently challenged with O. ochengi- infective larvae whilst raised in a fly-proof house. Post-challenge adult parasite and microfilaria development, IgG1 and lgG2 subclass antibodies response to Ov10/Ov11 recombinant Onchocerca antigens, and peripheral blood lymphocyte proliferative responses to O. ochengi crude antigens were studied over a 1-year period. The vaccinated-challenged animals had 83–87% less adult O. ochengi parasites than non-vaccinated-challenged animals. IgG1 and lgG2 antibodies to Ov10/Ov11 recombinant Onchocerca antigens were invoked by non-vaccinated-challenged animals but not by most (80%) of the vaccinated-challenged animals. These findings support the idea of cross-protection (zooprophylaxis) due to inoculation of humans with O. ochengi -infective larvae under natural transmission conditions in endemic areas. [ABSTRACT FROM AUTHOR]

Background In 1993 extremely high levels of birch-pollen were recorded in Stockholm, Sweden. This provided an opportunity to evaluate the effects of aeroallergen exposure (exp.) on the early immune response. Objective To assess the influence of exp. to birch-pollen during pregnancy and infancy on the allergen-specific IgE- and IgG4-antibody (ab) response and the development of atopic disease in children. Methods A total of 970 children with atopic heredity and born in Stockholm 1992, 1993 or 1994 were investigated at age 4.5–5 years. They were divided into five groups; high-dose exp. at 1 year of age, high-dose exp. at 0–3 months, low-dose exp. at 0–3 months, high-dose exp. during pregnancy and low-dose exp. during pregnancy. The children were examined and skin prick tested with inhalant and food allergens. IgE abs (against birch-pollen and recombinant Bet v 1(rBet v1)) and IgG4 abs (against rBet v 1) were analysed in serum. All children were assembled in one group to assess the effects of different ab responses (IgE/IgG4) on the development of atopic disease. Results Children exposed to high doses of birch-pollen during the first 3 months of life more often had detectable levels of IgG4 abs to rBet v 1 than the children in the other groups ( P<0.001), independent of sensitization to birch. Overall, the risk of allergic rhinoconjunctivitis was increased among children sensitized to birch-pollen and appeared more pronounced in children without detectable levels of IgG4 ab to rBet v 1 (Odds ratio 9.4; 95% Confidence interval: 5.5–16.1). IgE sensitization to birch-pollen seemed to have a stronger influence on the development of atopic disease than the IgG4-ab response. Conclusion Exposure to high doses of inhalant allergens during the early postnatal period is associated with detectable levels of allergen-specific IgG4 ab even at 5 years of age. An immune modulating effect by IgG4 on symptoms of allergic rhinoconjunctivitis is suggested in children sensitized to birch. [ABSTRACT FROM AUTHOR]

Background: A majority of patients with cystic fibrosis (CF) become colonised with Aspergillus fumigatus (Af.), but only a minority develops allergic bronchopulmonary aspergillosis (ABPA). ABPA is associated with increased levels of specific immunoglobulin G (IgG) anti-Af. antibodies with a characteristic IgG subclass distribution. We examined whether this characteristic immune response was under the influence of GM and KM allotypes, which are genetic markers (antigenic determinants) on gamma- and kappa-light chains, respectively. Methods: Sera from 233 CF patients were typed for seven GM determinants and two KM determinants. The types were correlated to IgG subclass anti-Af. antibody levels and to the presence or absence of Af. colonisation as well as ABPA. Results: The IgG2 antibody level was significantly higher in heterozygous GM (1,2,17 23 5,21 and 1,3,17 23 5,21) compared to homozygous GM allotypes (p=0.02). Patients with the same allotypes tended to have higher IgG1 (p=0.051). In patients with ABPA, being heterozygous for G1M and G3M was linked to higher IgG4 and lower IgG3 as compared to the other genotypes. The KM markers did not influence the antibody levels. The allotype GM(3 23 5), associated with atopic bronchial asthma, tended to make a relatively larger group in ABPA patients compared to non-ABPA and patients not colonised with Af. (p=0.09). Conclusions: An influence of the GM allotypes on the immune response to Af. and on the development of ABPA in patients with CF is suggested. [Copyright &y& Elsevier]

Visceral leishmaniasis (VL), caused by Leishmania infantum, is an important disease of domestic dogs. Here, we present data on the IgG subclass antibody response to crude L. infantum antigen in a cohort of naturally infected Brazilian dogs. Specific IgG1–IgG4 responses could be detected in 98, 58, 70 and 82%, respectively of 57 dogs that were seropositive for specific IgG. Levels of all IgG subclasses were strongly inter-correlated. Levels of all IgG subclasses increased at the time of seroconversion, before reaching a plateau after several months. Levels of all IgG subclasses were higher in sick dogs than healthy dogs, and levels of all except IgG2 were higher in parasite-positive (by PCR) than parasite-negative dogs. However, levels of IgG2 relative to IgG1 were lower in sick or parasite-positive dogs compared to healthy or parasite-negative infected dogs. In contrast to previous studies, the results suggest that canine VL is associated with upregulation of specific antibody of all IgG subclasses, particularly IgG1, IgG3 and IgG4. [Copyright &y& Elsevier]

Summary Background The character of immune responses to allergens during the first years of life may decide whether the individual will become tolerant or develop allergy later in life. Objective To study the development of immune responses to the seasonal inhalant allergen birch over the first 7 years of life. Methods Blood samples were obtained from 21 children who were followed prospectively from the second to the seventh pollen season of life. Birch-induced cytokine production and IgG subclass antibodies to rBet v 1 were analysed with ELISA, mRNA expression with real time PCR, IgE antibodies to birch with Magic LiteTM and birch-induced mononuclear cell proliferation with 3 H-thymidine incorporation. Results Birch-induced IFN-γ and IL-10 production increased with age, both in atopic and non-atopic children, while birch-induced IL-13 production decreased. The two children who were sensitized and developed clinical allergy to birch showed persistent IL-4 and IL-5 production and IL-9 mRNA expression, as well as Th2-associated IgG4 responses. Transient Th2-like responses were observed among the other children. Proliferative responses and IgG1 antibodies were seen in all children. Conclusions Immune responses to birch can be demonstrated in all children, during the first 7 years of life, regardless of atopic status. A transient early Th2-like response is down-regulated after the fourth pollen season, except in children who develop clinical allergy to the particular allergen. [ABSTRACT FROM AUTHOR]

There are few studies on allergen‐induced cytokine production in allergic children, and little is known of antigen‐specific cytokine regulation of human immunoglobulin (Ig) G subclass antibody responses. An association with T‐helper 1 (Th1)‐like immunity and complement‐activating antibodies remains to be demonstrated in humans. We have previously observed that atopic symptoms are associated with high levels of IgG subclass, especially IgG4, antibodies to birch and β-lactoglobulin. The differences were seen early in life for the food allergen and increased with age for the inhaled allergen. The aim of this study was to investigate the association between atopic symptoms, birch allergen‐, and β‐lactoglobulin‐induced cytokine production in peripheral blood mononuclear cells (PBMC), and serum IgE and IgG subclass antibody responses to these allergens in children in order to further clarify the role of Th1‐ and Th2‐like immunity in responses to various antigens. PBMC from 55 eight‐year old children, who had been followed prospectively from birth, were stimulated with birch‐ and β‐lactoglobulin. Production of interleukin (IL)‐5, IL‐6, IL‐10, IL‐13 and interferon (IFN)‐γ was analysed by ELISA and expression of IL‐4 and IL‐9 mRNA by semiquantitative reverse transcriptase–polymerase chain reaction (RT‐PCR). IgG subclass antibody levels to birch‐ and β‐lactoglobulin in serum were determined by ELISA, and IgE antibodies by Magic‐Lite™ and CAP‐RAST™, respectively. Birch‐induced expression of IL‐4, but not of the other cytokines, was associated with IgE antibodies to birch. Furthermore, the IL‐4 expression and IL‐6 production correlated with serum IgG4 antibody levels to this allergen, and IFN‐γ... [ABSTRACT FROM AUTHOR]

Immune responses to allergens in young children include both Th1‐ and Th2‐like immunity, which may regulate the secretion of immunoglobulin (Ig) G subclass antibodies differently. The time, route and level of exposure to an allergen may be decisive with regard to whether sensitization or tolerance will ensue. To study this, we investigated the development of IgG subclass antibodies to food and inhalant allergens during childhood. The study group comprised a cohort of 96 children participating in a prospective study. IgG subclass antibodies to ovalbumin, Bet v 1 and cat dander were analyzed at birth, 6 and 18 months and 8 years by ELISA. IgG1 and IgG3 subclass antibodies to ovalbumin peaked at 18 months and then declined up to 8 years of age, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increased with age. Exposure to cat and birch tended to be associated with high antibody levels to those allergens, whereas antibody levels to ovalbumin were not related to exposure to egg. The presence of positive skin prick tests and circulating IgE antibodies correlated with high levels of IgG subclass antibody responses to the allergens. Atopic symptoms were associated with high levels of IgG subclass, particularly IgG4, antibodies to the allergens. The difference in antibody levels between atopic and non‐atopic children was most marked at 6 months for ovalbumin. For the seasonal inhalant allergen birch, the difference was apparent from 18 months, whereas a difference in antibody levels to the perennial inhalant allergen cat was already present at 6 months. In conclusion, IgG subclass antibodies to food allergens peak in early infancy and are then down‐regulated, whereas antibodies to the inhalant perennial allergen cat, but not the inhalant seasonal allergen birch, increase with age. Atopy is associated with high levels of IgG subclass, particularly... [ABSTRACT FROM AUTHOR]

IgG subclasses of antibodies to the dietary antigens gliadin, glyegli (a gluten component), ovalbumin (OA) and β-lactoglobulin (BLG) were quantified in children with coeliac disease (CD). nine on a gluten-containing diet, 15 on a gluten-containing diet. and in appropriate controls. In addition. total serum IgG-subcIasses were measured, lgGl and lgG3 antibodies to gluten and glycgli were detected in 9/9 and 8/9 CD- patient on a gluten-containing diet, respectively, and in 4/15 and 6/15 patients on a gluten- Free diet. None of the controls had appreciable levels of lgG I antibodies and only 1/22 of the controls had IgG3 antibodies to gliadin and glycgli. IgG2 and lgG4 antibodies to the same antigens were found in a few coeliacs and controls. Consecutive samples from coeliac children (8 patients) showed a clear relation between the exposure to gluten and a rise in IgG1 (8/8) and IgG3 antibody levels (718). In contrast, IgG antibodies to OA and RIG were almost exclusively of the IgGI and lgG4 subclasses. The highest levels were found in children with CD, hut the differences between the groups were not significant. Total serum IgG subclasses did not differences between the groups, but the IgG2 and lgG4 levels in most coeliac children were low. The production of IgG1 and IgG3 antibodies to gluten components may be an important precondition for the development of coeliac disease in susceptible individuals. [ABSTRACT FROM AUTHOR]

The IgG subclass response was evaulated by a sensitive allergen- and stibclass-specific solid phase immunoradiometric assay during a 1-year placebo-controlled, double-blind study of immunotherapy with Cladosporium herbarum in 22 adult asthmatics. The IgG response was mainly restricted to subclasses 1 and 4 but a few patients were IgG2 and IgG3 responders. An intense and early IgG, response was observed during the first clusters of injection followed by a levelling down of the titer. The IgG4 response had a later onset and showed slowly increasing levels during the 12 months of immunotherapy. The graded clinical efficacy estimated by symptom-medication score was significantly correlated to the preseasonal IgG1 value, with high values indicating a deleterious response of immunotherapy (deterioration of disease activity). Likewise, the fold increase of IgG1 and IgG4 after two clusters of immunotherapy (i.e. after 4 weeks) was significantly related to the clinical outcome. Little or no increase of IgG1 and IgG4 was associated with improvement, i.e. decrease in symptom-medication score. The magnitude of the IgG, response during the dose-increase phase was directly correlated to the number of systemic side effects. No relation of IgG1, IgG4 or IgG4/IgG4 ratio to changes in the IgE-mediated parameters (skin prick test, bronchial challenge and circulating specific IgE) was observed. Our data, which are based on few patients and only one allergen system, do not support the hypothesis of IgG acting as blocking antibody being the immunologic mechanism of immunotherapy. The association between high IgG4 values and a deleterious efficacy of immunotherapy might be caused by IgG4 acting as sensitizing antibodies. This explanation, however, is opposed by the lack of relation to systemic side effects. [ABSTRACT FROM AUTHOR]

IgG subclass antibodies to two dietary antigens, ovalbumin (OA) and beta-lactoglobulin (BLG) were measured with quantitative ELISA-techniques in 16 patients with atopic dermatitis (AD) (6-21 years old) and closely matched controls. In addition, IgE-antibodies to OA, BLG and milk were determined with RAST. IgG subclass antibodies were frequently detected in IgG1 and IgG4 for both AD-patients and controls, quantitatively dominated by IgG4. The IgG4 anti-BLG antibody levels were significantly higher (P < 0.001) in AD-patients (median: 1.1 μg/ml, range: 0-24.0 μg/ml) than in controls (median: 0.05 μg/ml, range: 0-1.05 μg/ml). No relation was found between IgG4 anti-BLG antibody levels, levels of IgE antibodies to milk or BLG, or severity of disease. [ABSTRACT FROM AUTHOR]

Background: Exposure to allergens early in life may have an impact on the incidence of allergy many years later, but the kinetics of the immune responses have still not been studied prospectively. Therefore, we wanted to study the development of immune responses of the Th1 and Th2 type to birch over the first pollen seasons. Material and Methods: Blood samples were obtained from 21 prospectively followed children during the second to the seventh pollen season of life. IgG subclass antibodies to rBet v 1 were analyzed by ELISA, IgE antibodies to birch with Magic Lite[sup TM] and birch-induced mononuclear cell proliferation by [sup 3] H-thymidine incorporation. Results: Proliferative responses and IgG1 antibodies were commonly seen both in children with and without allergic symptoms and sensitization to birch. Most nonsensitized children had a transient IgG4 antibody response, which was downregulated after the third pollen season, while the titers of this Th2-associated subclass increased with age in sensitized children with clinical symptoms to birch. Conclusions: Immune responses to birch can be demonstrated in children regardless of atopic status. A transient early Th2-like response is downregulated after the third pollen season in nonatopic but not atopic children.Copyright © 2001 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

• AS cases have higher levels of both anti-filarial and auto-antigen specific IgG4. • Plasma levels of anti-filarial and self-reactive IgA are lower in AS cases. • Anti-filarial IgG4 levels and levels of IgG4 against auto-antigens are positively co-related. Lymphatic filariasis, a chronic disfiguring disease exhibits complex pathology. Based on different clinical manifestations, infected individuals are categorized into asymptomatic-carriers and chronic-patients. The mechanism behind differential clinical outcomes remains unclear. Roles of filaria-specific B cell responses in filariasis have been documented, whereas the contribution of B1 cell response and poly-specific IgG and IgA in the context of clinical filariasis is not deciphered. In this study, we measured the poly-specific IgG and IgA levels in different clinical categories of filariasis. Asymptomatic-carriers exhibited increased IgG4 antibodies against both filarial-antigens as well as auto-antigens compared to other clinical categories, although IgG against these auto-antigens remained lower. IgA levels against both filarial and auto-antigens were decreased in asymptomatic-carriers. A positive correlation between anti-filarial IgG4 and IgG4 against auto-antigens were observed, suggesting the synergistic role of poly-specific natural IgG4 with anti-filarial IgG4 in blocking the pathogenesis in asymptomatic microfilarial cases. [ABSTRACT FROM AUTHOR]