IgE Antibody Production Research Articles

Pathological Mechanisms Underlying IgE-mediated Food Allergy

Food allergy is an immune disease triggered by abnormal immune responses against harmless antigens that enter through our gut lumen. There are two major pathways that contribute to the food allergic symptoms: IgE-mediated and non IgE-mediated. Among all food allergy cases that have already been discovered, IgE-mediated mechanisms are responsible for over 80-90% of the cases. The IgE-mediated mechanisms include epithelium damage, T helper 2 cell induction, IgE antibody production, and the final symptoms caused by the effector cells. We also discovered that there may exist a potential relationship between B cell metabolism and the IgE production, which ultimately leads to food allergy. At the same time, since more and more people now enjoy more diverse food sources, issues regarding food allergy are outbursting these years as people’s exposure to different food proteins and antigens rapidly increase. It is shown that the United States government is losing billions dollars annually to cover the lost caused by food allergy. Given the worldwide prevalence of the food allergy and the increasingly unhealthy lifestyles of many people, it is highly crucial for us to understand the fundamental mechanisms underlying the IgE-mediated food allergy, which is the most common and influential pathway that risks millions of lives. Therefore, this Review goes over the basic mechanisms underlying the IgE-mediated food allergy, namely how epithelium damage, T helper 2 cell induction, IgE antibody production, effector cell activation, and B cell metabolism lead to the final symptoms of food allergy.

PD-1 blockade in T follicular helper cells protects mice from peanut allergy by promoting production of low-affinity antibodies

Abstract Food allergy, such as peanut allergy can cause life-threatening anaphylaxis. While T follicular helper (Tfh) cells play a major role in production of allergen-specific IgE and IgG antibodies, the immunologic mechanisms that regulate the production of antibodies that mediate anaphylaxis are not well understood. While PD-1 is highly expressed on Tfh cells, our knowledge is limited regarding the role of the molecule in Tfh cells. Thus, the objective of this study was to investigate the roles of PD-1 in allergic immune responses using a mouse model of peanut allergy. Naïve wild-type mice were exposed to peanut flour intranasally (i.n.) and then challenged by intraperitoneal (i.p.) injection of peanut extract. The mice exposed i.n. to peanut flour produced peanut-specific IgE and IgG antibodies and developed anaphylaxis when challenged i.p. with peanut extract. PD-1 blockade with anti-PD-1 treatment Tfh and germinal center B cell numbers in mice exposed to peanut flour. Nonetheless, anti-PD-1 or anti-PD-L1 fully protected mice from anaphylaxis. Anti-PD-1 or genetic deficiency of PD-1 in CD4+ T cells reduced and increased levels of peanut-specific IgE and IgG, respectively. Anti-PD-1 promoted production of low-affinity IgE and IgG antibodies with no effect on high-affinity antibodies. By passive cutaneous anaphylaxis, peanut-specific antibodies generated in anti-PD1 treated mice failed to induce anaphylaxis, and plasma from these mice prevented anaphylaxis. Therefore, blockade of the PD-1 pathway is protective against allergic immune responses. The interaction between Tfh cells and B cells may play a pivotal role in controlling antibody quality and clinical manifestation of allergic diseases.

Exposure to SARS-CoV-2 spike protein induces antigen specific IgE and basophil activation

Abstract The spike glycoprotein of SARS-CoV-2 (S) has been used as a main target antigen for vaccine design. There are concerns of vaccine-induced allergies, but mostly about allergic responses to the adjuvant. We, however, found that repetitive exposure to SARS-CoV-2 spike, not Nucleocapsid (N) protein, can induce robust type 2 inflammation in the airway of mice, which is exacerbated by the presence of house dust mite allergens. This type 2 inflammation is accompanied with elevated IgE and neutralizing antibody production. To further test whether spike glycosylation influences these responses, we compared the immunogenicity of insect cell expressed spike (in-S), mammalian cell expressed spike (m-S) and deglycosylated spike (dg-S). With intranasal treatment, in-S induced high levels of anti-spike/S1 specific IgE, while m-S and dg-S induced detectable NAb titers as determined by pseudo-virus (PV) neutralization assays. Moreover, exposure to in-S induced a significant amount of IgE+ basophils in the spleens and lungs of the mice. These spike-induced phenotypes are dependent on the TLR4/MyD88 and STAT6 signaling pathways. When delivered via intramuscular immunization following the priming/boosting protocol, spike protein induced high levels of antigen-specific IgE and IgE+ basophils. Of note, in-S induced the highest level of anti-spike/S2 IgE. However, interestingly, deglycosylation of spike antigen resulted in enhanced induction of NAbs and spike-specific CD8+ T cells following intramuscular immunization. Together, our data suggests that vaccination with SARS-CoV-2 spike may induce antigen-specific allergic response, while immunization with the deglycosylated spike protein may help enhance protective immune responses. Supported by National Institutes of Health (R01 AI151139, R56 AI146226 and P20 GM130555). W. Huang also received research support from MegaRobo Technologies Corporation.

Recent Progress in Traditional Chinese Medicines and Their Mechanism in the Treatment of Allergic Rhinitis.

Objective To conduct a systematic review on the mechanism of action and use of traditional Chinese medicines (TCM) in allergic rhinitis treatment. Background Allergic rhinitis (AR) is a type I allergic disease of the immune system induced by immunoglobulin E mediated inflammation and is characterized by sneezing, nasal itching, paroxysmal nasal obstruction, mucosal edema, cough, and rhinorrhea. More than 500 million people have been affected by rhinitis worldwide in the past 20 years, leading to negative effects on health, quality of life, and social relationships. Currently, the trending medicines used in the case of AR include intranasal corticosteroids and oral H1 antihistamines, which are given as combinatorial medicines supplemented with immune therapy. These medications have been found to be very effective in either the short term or long term; however, they have been found to possess some serious side effects. Search Methodology. The information in this article on classical and traditional Chinese medications used to treat AR was derived from original papers and reviews published in Chinese and English language journals. Two Chinese databases (Wanfang and CNKI) and three English databases (Cochrane Library, PubMed, and Embase) were utilized for data gathering. Results Traditional Chinese remedies have been identified to influence the production of cytokines such as IL-5 and IL-6, which are key mediators of eosinophilic inflammation, TNF-α, which stimulates TH2 cells at the site of inflammation, and NF-кB, which is required for cytokine and IgE antibody production. TCM has also been shown to be successful in lowering histamine levels, preserving histological changes by decreasing the thickness of the lamina propria, and downregulating the expression of Orai1, STIM1, and TRYC1, showing low expression of Ca+2 channel proteins. Conclusion In this review, we discussed a series of classical, traditional Chinese medications, including Centipeda minima, Scutellaria baicalensis, licorice root (Glycyrrhiza uralensis), and others, as potential antiallergic agents and investigate their in vivo effect upon the production of cytokines and release of histamines for allergic rhinitis treatment.

Sensitisation and allergic reactions to alpha-1,3-galactose in Podlasie, Poland, an area endemic for tick-borne infections

Purpose Ticks transmit several pathogens and seem implicated in the production of specific IgE antibodies to alpha-1,3-galactose (α-gal sIgE). They cause delayed and immediate allergy to mammalian meat and medication including antivenoms, vaccines and monoclonal antibodies. Methods We assessed the prevalence of α-gal sIgE in forest workers and healthy controls in the Podlasie voivodeship, north-eastern Poland; the relationship between α-gal sIgE and allergy to α-gal-containing products; the correlation between α-gal sIgE and anti-Borrelia burgdorferi and anti-tick-borne encephalitis virus (TBEV) antibodies; the relationship between α-gal sIgE and markers of infection with lesser-known pathogens transmitted by ticks such as Anaplasma phagocytophilum. Results Production of α-gal sIgE was closely related to tick bites. The odds ratio for detectable α-gal sIgE was 9.31 times higher among people with a history of tick bites (OR 9.3; p < .05). There was no correlation with the history of TBE, Lyme disease or human granulocytic anaplasmosis. However, serum α-gal sIgE correlated with anti-TBEV IgM antibodies in CSF. There was a strong correlation between α-gal sIgE and total IgE and sIgE to pork and beef. Conclusions Our data support the link between I.ricinus ticks and the production of α-gal sIgE and confirm that the pathogens carried by ticks we examined for do not seem implicated in this immune response.

Tick Intrastadial Feeding and Its Role on IgE Production in the Murine Model of Alpha-gal Syndrome: The Tick "Transmission" Hypothesis.

Recent studies have provided strong evidence indicating that lone star tick bites are a cause of AGS (alpha-gal syndrome, also known as red meat allergy RMA) in humans. AGS is characterized by an increase in IgE antibody production against galactose-alpha-1,3-galactose (aGal), which is a common glycan found in mammalian tissue, except in Old World monkeys and humans. The main causative factor of AGS, the lone star tick (Amblyomma americanum), is broadly distributed throughout the east and midwest of the United States and is a vector of a wide range of human and animal pathogens. Our earlier glycomics study of the salivary glands of partially fed male and female ticks revealed relatively high levels of aGal epitopes. In this study, we found that partially fed males of A. americanum on bovine blood, which engage in multiple intrastadial feedings, carry a large amount of aGal in the salivary glands. In our current work, we aimed to test whether ticks mediate the transmission of the aGal sensitizer acquired from nonhuman blood to humans in the intrastadial host switch (referred to as the “transmission” hypothesis). To test this hypothesis, we used an alpha-galactosyltransferase knockout mutant mouse (aGT-KO) model system infested with ticks that were unfed or partially fed on bovine blood. Based on the levels of total IgE and specific IgG and IgE antibodies against aGal after tick feedings, aGT-KO mice significantly responded to tick feeding and injection of aGal (Galα1-3Galβ1-4GlcNAc) conjugated to human serum albumin or mouse serum albumin (aGal-HSA or aGal-MSA) by increasing total IgE and aGal-specific IgE levels compared to those in C57BL/6 control mice. All of the treatments of aGT-KO mice involving the feeding of partially fed and unfed ticks functioned as sensitizers that increased the levels of specific IgE against aGal, with large individual variations. The data in this study do not support the “transmission” component of AGS, although they confirmed that aGT-KO mice can be used as a model for RMA studies.

Bcl6-expressing Foxp3+ T cells Promote Production of Antigen-Specific IgE in Response to Airborne Ragweed Pollen Exposure

The transcription factor Bcl6 is essential for development and differentiation of T follicular helper (Tfh) cells in draining lymph nodes (dLNs), which are pivotal for antigen-specific IgE antibody production. During immune responses, a subset of Foxp3+ regulatory T cells that express Bcl6, namely T follicular regulatory T (Tfr) cells, is also generated in dLNs. Our knowledge is limited regarding the roles of these Tfr cells in allergic immune responses.

Place of residence, gender, month of birth and age influence on the concentration of specific IgE antibodies in serum. The Epidemiology of Allergic Diseases in Poland (ECAP survey): part three.

IntroductionSpecific immunoglobulins E (sIgE) are important parameters to estimate the severity of allergic diseases.AimTo determine the influence of gender, age and place of residence on the concentration of specific IgE antibodies in serum.Material and methodsThe concentration of sIgE antibodies against allergens of Dermatophagoides pteronyssinus, cat dander, timothy grass, Alternaria alternata were determined in serum of 4077 respondents randomly selected from 8 regions (ECAP study). The positive results of sIgE (≥ 0.35 IU/ml) were correlated with answers to ECAP questionnaires.ResultsIgE antibodies are less frequently detected in respondents living in the country (p < 0.05 to p < 0.005); and they are less frequently detected in respondents living in cities of hardly industrialised regions than in respondents living in cities of industrialised regions (D. pteronyssinus p < 0.05, cat dander p < 0.01). IgE antibodies are more frequently detected in men (p < 0.005 to p < 0.001). IgE antibodies are more frequently detected in respondents born in May-July (timothy grass p < 0.005, Alternaria alternata p < 0.005) and less frequently detected in respondents born in August-October (timothy grass p < 0.005, Alternaria alternata p < 0.05).ConclusionsCharacteristics of the urban environment, non-specific factors and gender affect the concentration of specific IgE antibodies in serum. Influence of seasonal allergens within the first months of life and/or in the course of the foetal period alters the production of specific IgE antibodies.

D031 LONGITUDINAL ANALYSIS OF SINGLE B CELLS, IGE ANTIBODIES, AND PLASMA IN A PEANUT ALLERGIC SUBJECT

Our understanding of monoclonal, allergen-specific IgE antibodies has been hindered by the scarcity of circulating IgE-producing B cells, which are rare even in allergic individuals. The potential to isolate single B cells producing IgE antibodies and class switch these antibodies to IgG4 antibodies, like those that increase with allergen-specific immunotherapy, could be of great therapeutic value.

Intrinsic and extrinsic regulation of IgE B cell responses.

Stringent regulation of IgE antibody production is critical for constraining allergic responses. This review discusses recent advances in understanding cell-intrinsic and extrinsic mechanisms that regulate the genesis and fate of IgE B cells. B cell-intrinsic regulation of IgE is orchestrated by the IgE B Cell Receptor (BCR). Through its antigen-independent signaling and low surface expression, the IgE BCR drives IgE B cells to differentiate into short-lived plasma cells and/or undergo apoptosis, restricting IgE-expressing cells from entering long-lived compartments. The pivotal extrinsic regulators of IgE responses are T follicular helper cells (TFH). TFH produce IL-4 and IL-21, which, respectively, are the major activating and inhibitory cytokines for IgE class-switching. Other newly identified T follicular subsets also contribute to IgE regulation. Although IgE responses are normally constrained, recent studies suggest that specific conditions can induce the formation of IgE responses with enhanced affinity or longevity, effectively 'breaking the rules' of IgE regulation.

Follicular T Helper and Breg Cell Balance in Severe Allergic Asthma Before and After Omalizumab Therapy.

BackgroundSevere allergic asthma (SAA) is based on type 2 (T2-high) immune responses to allergens promoting type 2 T helper (Th2) cell cytokine responses and production of IgE antibodies. Omalizumab was the first biological drug licensed for clinical use in the management of IgE-mediated SAA. Despite emerging evidence supporting the prominent role of follicular T cells (Tfh), Breg and Treg subsets, in the development and progression of SAA, no data are available on the impact of omalizumab therapy.MethodsTen SAA patients monitored at the Respiratory Diseases Unit of Siena University Hospital and ten healthy sex- and age-matched controls were enrolled in the study. Clinical and functional parameters were collected at baseline (T0) and after 6 months of therapy (T6). Cellular population analysis was determined through multicolour flow cytometry.ResultsSAA patients showed higher percentages of Th17.1, Tfh and Tfh2 while CD24hiCD27hi Breg cell, Treg and Tfr percentages were significantly lower than in controls. Higher percentages of Tfh2 in patients with nasal polyps than in those without and in controls were observed. At T6, significant decreases in Tfh and Tfh2 compared with T0 were observed. A slightly significant increase in Teffs was reported at T6 compared to T0. ΔIgE levels in serum were correlated with ΔCD19+CD24+CD27+ Breg cell percentages (r = − 0.86, p = 0.0022).ConclusionsOur data explored the changes in Tfh cells, Tregs and Bregs in severe asthma. The restoration of immunological imbalance in SAA patients after omalizumab is certainly intriguing and represents a glimpse into the comprehension of immunological effects of treatment.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40291-021-00545-3.

Prevalence of IgE-Mediated Food Hypersensitivity to Cereals and Beans Based on Skin Prick Test in Children with Celiac Disease.

BACKGROUND Celiac disease is a non-IgE mediated food allergy, which can cause extensive villus atrophy. Because of increased food allergen absorption, there are elevated IgA and IgG antibodies in these patients, so there is a concern about IgE antibody production against wheat and other cereals. METHODS In this study, we evaluated IgE-mediated hypersensitivity to wheat, rice, and other cereals in children with celiac disease. RESULTS 22 patients (50%) had at least one positive skin prick test to food allergens. The most frequent food allergen was peanut (31.8%), followed by wheat (18.2%), corn (9.1%), and rice (4.5%). The results revealed no significant correlation between age, sex, and the results of the skin prick test (p >0.05). The correlation between diagnosis time of celiac disease and results of skin prick test was also not significant statistically (p >0.05). CONCLUSION Because of the high prevalence of IgE mediated hypersensitivity to cereals and beans in children with celiac disease, a skin prick test might be considered in these patients, especially in refractory cases.

A2 Bovine Milk and Caprine Milk as a Means of Remedy for Milk Protein Allergy

A new type of cow’s milk, called A2 milk, has appeared in the dairy aisles of supermarkets in recent years. Cows’ milk generally contains two major types of beta-casein as A1 and A2 types, although there are 13 genetic variants of β-casein: A1, A2, A3, A4, B, C, D, E, F, H1, H2, I and G. Studies have shown that A1 β-casein may be harmful, and A2 β-casein is a safer choice for human health especially in infant nutrition and health. The A2 cow milk is reportedly easier to digest and better absorb than A1 or other types of milk. The structure of A2 cow’s milk protein is more comparable to human breast milk, as well as milk from goats, sheep and buffalo. Digestion of A1 type milk produces a peptide called β-casomorphin-7 (BCM-7), which is implicated with adverse gastrointestinal effects on milk consumption. In addition, bovine milk contains predominantly αs1-casein and low levels or even absent in αs2-casein, whereby caprine milk has been recommended as an ideal substitute for patients suffering from allergies against cow milk protein or other food sources. Since goat milk contains relatively low levels of αs1-casein or negligible its content, and αs2-casein levels are high in the milk of most dairy goat breeds, it is logical to assume that children with a high milk sensitivity to αs1-casein should tolerate goat milk well. Cow milk protein allergy (CMPA) is considered a common milk digestive and metabolic disorder or allergic disease with various levels of prevalence from 2.5% in children during the first 3 years of life to 12–30% in infants less than 3 months old, and it can go up to even as high as 20% in some countries. CMPA is an IgE-mediated allergy where the body starts to produce IgE antibodies against certain protein (allergens) such as A1 milk and αs1-casein in bovine milk. Studies have shown that ingestion of β-casein A1 milk can cause ischemic heart disease, type-1 diabetes, arteriosclerosis, sudden infant death syndrome, autism, schizophrenia, etc. The knowledge of bovine A2 milk and caprine αs2-casein has been utilized to rescue CMPA patients and other potential disease problems. This knowledge has been genetically applied to milk production in cows or goats or even whole herds of the two species. This practice has happened in California and Ohio, as well as in New Zealand, where this A2 cow milk has been now advanced commercially. In the USA, there have been even promotions of bulls, whose daughters have been tested homozygous for the A2 β-casein protein.

Evaluation of sensitization to the crude extract of Dermatophagoides farinae and its derived allergens, Der f 2 and Zen 1, in dogs with atopic dermatitis in Southern Brazil

BackgroundAtopic dermatitis is associated with the production of IgE antibodies against environmental allergens and allergens of the house dust miteDermatophagoides farinae are frequently implicated in the disease. ObjectivesWe aimed to observe the allergen-specific IgE against crudeD. farinae, Der f 2 and Zen 1 in dogs with atopic dermatitis and report if these dogs are in contact with material that could shelter mite allergens. Methods100 dogs with clinical diagnosis of atopic dermatitis were included after exclusion of other forms of pruritic skin disease and dogs that already received specific or non-specific immunotherapy. These dogs were of different breeds and ages and they were presented at a veterinary teaching hospital and a private service of veterinary dermatology, both located in Curitiba, Southern Brazil. At the time of anamnesis, some questions were applied to know the possibility of these dogs having had contact with furniture and textile material which could shelter house dust mites. Sera samples were obtained and further analyzed by ELISA assay to measure serum IgE levels against these allergens with an established cut-off of 0.200 IgE optical density. ResultsThe allergen-specific IgE positivity against crudeD. farinae (92 %) and Zen 1 (77 %) was higher than Der f 2 (56 %). There was a correlation in sensitization to crude D. farinae and Zen 1 that was not observed between crude D. farinae and Der f 2 and Der f 2 and Zen 1. The sensitization to D. farinae and its allergens was associated with an unrestricted exposition to furniture and textile material. Conclusion & clinical relevancedogs with atopic dermatitis are frequently sensitized to D. farinae and its allergens, Der f 2 and Zen 1, may be considered major allergens in these dogs. Zen 1 may be the main allergen responsible for the sensitization to crude D. farinae.

A Transcription Factor Blimp1 in CD4+ T cells Promotes Type 2 Immune Responses in the Lungs While it Suppresses IgE Antibody Production in Mice

Allergic immune responses generally involve generation of antigen-specific type 2 CD4+ T cells and production of IgE antibodies. A transcription factor B lymphocyte-induced maturation protein-1 (Blimp1) regulates plasma cell development and effector functions of T cells. However, little information is available regarding the roles of Blimp1 in allergic immune responses.

Increased Interleukin-4 in Farmers With Ascariasis in Rural Jember

Ascaris lumbricoides is nematode which often infest human in the world. The infestation of A. lumbricoides in the human will trigger the formation of Th2 immune responses through increased interleukin-4 released by innate immune cells. Th2 immune response generates B lymphocyte cells to produce IgE antibodies to eliminate A. lumbricoides. Therefore, IL-4 is a marker of Th2 immune response. The purpose of this study was to determine the prevalence of ascariasis and an increase of IL-4 in planters infested with A. lumbricoides as a marker of Th2 immune response. Our study was observational analytic with cross sectional design. 230 planters who were willing to be involved in the study gave stool samples for the diagnosis of ascariasis. 20 people who were positive for ascariasis and 20 people who were negative selected randomly for blood plasma samples. IL-4 levels in blood plasma were measured using ELISA. Differences in IL4 levels between positive and negative ascariasis were analyzed by the Mann Whitney statistical test with p value ≤ 0.05. The prevalence of ascariasis among planters in rural area of Jember was 16,52% which was included low prevalence. Univariate analysis showed that the mean and median levels of IL-4 ascariasis were greater than those of healthy planters. Mann Whitney test results showed that there were differences in levels of IL-4 between ascariasis and healthy planters (p≤0.05). Increased levels of IL-4 in planters with ascariasis indicate that A. lumbricoides infection triggers the formation of Th2 immune response as a mechanism for eliminating A. lumbricoides. Keywords: Interleukin-4, A. lumbricoides, Th2 immune response.

Thaumatin-Like Protein (Pru av 2) Is a Cherry Allergen That Triggers Percutaneous Sensitization in Mice

Numerous recent studies have suggested that food allergens enter the skin and predispose individuals to food allergies through the production of IgE antibodies in the body. Cherries are a popular fruit eaten worldwide. However, cherries are an allergenic food and percutaneous sensitization with cherry allergens through the perioral region may occur while ingesting cherries. The identity of the cherry protein that triggers percutaneous sensitization in humans or animal models remains unknown. In this study, the backs of BALB/c mice were shaved and crude cherry extracts containing sodium dodecyl sulfate were applied to the skin. Thereafter, the cherry-specific IgE and IgG1 antibodies generated and secreted in response to the epidermal application were measured using an enzyme-linked immunosorbent assay or immunoblotting. Skin exposure to cherry extracts elevated cherry-specific IgG1 levels. Application of fractionated and purified cherry proteins (antigen candidates for percutaneous sensitization) that bound to the IgG1 antibodies led to the identification of a thaumatin-like protein (Pru av 2). This molecule is known as the major cherry allergen that affects humans. In conclusion, our study identified Pru av 2 as a cherry allergen that triggers percutaneous sensitization in mice for the first time.

Investigating Immunization With Nucleotide Enzymes of Schistosoma mansoni: Nucleoside Diphosphate Kinase and Adenylosuccinate Lyase as New Antigenic Targets Against Schistosomiasis.

Schistosomiasis, caused by Schistosoma mansoni trematode worm, affects more than 1.5 million people in Brazil. The current treatment consists in the administration of Praziquantel, the only medicine used for treatment for more than 40 years. Some of the limitations of this drug consist in its inactivity against schistosomula and parasite eggs, the appearance of resistant strains and non-prevention against reinfection. Thus, the objective of this study was to evaluate the effect of immunization with recombinant functional enzymes of the purine salvage pathway of S. mansoni, Nucleoside Diphosphate Kinase (NDPK) and Adenylosuccinate Lyase (ADSL), to evaluate the host immune response, as well as the parasite load after vaccination. For this, Balb/c mice were divided into 5 groups: control (uninfected and untreated), non-immunized/infected, NDPK infected, ADSL infected, and NDPK + ADSL infected. Immunized groups received three enzyme dosages, with a 15-day interval between each dose, and after 15 days of the last application the animals were infected with 80 cercariae of S. mansoni. On the 47th day after the infection, fecal eggs were counted and, on the 48th day after the infection, the evaluation of leukocyte response, parasite load, antibody production, cytokines quantification, and histopathological analysis were performed. The results showed that immunizations with NDPK, ADSL or NDPK + ADSL promoted a discreet reduction in eosinophil counts in lavage of peritoneal cavity. All immunized animals showed increased production and secretion of IgG1, IgG2a, and IgE antibodies. Increased production of IL-4 was observed in the group immunized with the combination of both enzymes (NDPK + ADSL). In addition, in all immunized groups there were reductions in egg counts in the liver and intestine, such as reductions in liver granulomas. Thus, we suggest that immunizations with these enzymes could contribute to the reduction of schistosomiasis transmission, besides being important in immunopathogenesis control of the disease.

Structural Aspects of the Allergen-Antibody Interaction.

The development of allergic disease involves the production of IgE antibodies upon allergen exposure in a process called sensitization. IgE binds to receptors on the surface of mast cells and basophils, and subsequent allergen exposure leads to cross-linking of IgE antibodies and release of cell mediators that cause allergy symptoms. Although this process is quite well-understood, very little is known about the epitopes on the allergen recognized by IgE, despite the importance of the allergen-antibody interaction for the allergic response to occur. This review discusses efforts to analyze allergen-antibody interactions, from the original epitope mapping studies using linear peptides or recombinant allergen fragments, to more sophisticated technologies, such as X-ray crystallography and nuclear magnetic resonance. These state-of-the-art approaches, combined with site-directed mutagenesis, have led to the identification of conformational IgE epitopes. The first structures of an allergen (egg lysozyme) in complex with Fab fragments from IgG antibodies were determined in the 1980s. Since then, IgG has been used as surrogate for IgE, due to the difficulty of obtaining monoclonal IgE antibodies. Technical developments including phage display libraries have contributed to progress in epitope mapping thanks to the isolation of IgE antibody constructs from combinatorial libraries made from peripheral blood mononuclear cells of allergic donors. Most recently, single B cell antibody sequencing and human hybridomas are new breakthrough technologies for finally obtaining human IgE monoclonal antibodies, ideal for epitope mapping. The information on antigenic determinants will facilitate the design of hypoallergens for immunotherapy and the investigation of the fundamental mechanisms of the IgE response.

The Cellular and Molecular Bases of Allergy, Inflammation and Tissue Fibrosis in Patients with IgG4-related Disease.

IgG4-related disease (IgG4-RD) is a spectrum of complex fibroinflammatory disorder with protean manifestations mimicking malignant neoplasms, infectious or non-infectious inflammatory process. The histopathologic features of IgG4-RD include lymphoplasmacytic infiltration, storiform fibrosis and obliterative phlebitis together with increased in situ infiltration of IgG4 bearing-plasma cells which account for more than 40% of all IgG-producing B cells. IgG4-RD can also be diagnosed based on an elevated serum IgG4 level of more than 110 mg/dL (normal < 86.5 mg/mL in adult) in conjunction with protean clinical manifestations in various organs such as pancreato–hepatobiliary inflammation with/without salivary/lacrimal gland enlargement. In the present review, we briefly discuss the role of genetic predisposition, environmental factors and candidate autoantibodies in the pathogenesis of IgG4-RD. Then, we discuss in detail the immunological paradox of IgG4 antibody, the mechanism of modified Th2 response for IgG4 rather than IgE antibody production and the controversial issues in the allergic reactions of IgG4-RD. Finally, we extensively review the implications of different immune-related cells, cytokines/chemokines/growth factors and Toll-like as well as NOD-like receptors in the pathogenesis of tissue fibro-inflammatory reactions. Our proposals for the future investigations and prospective therapeutic strategies for IgG4-RD are shown in the last part.