Immunoregulatory Role of HLA-G in Allergic Diseases

Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients after in vitro incubation with the causal allergen. Elevated levels of soluble HLA-G molecules are detected in serum of patients with allergic rhinitis correlating with allergen-specific IgE levels, clinical severity, drug consumption and response to allergen-specific immunotherapy. HLA-G genetic polymorphisms confer susceptibility to allergic asthma development and high levels of soluble HLA-G molecules are found in plasma and bronchoalveolar lavage fluid of patients with allergic asthma correlating with allergen-specific IgE levels. Interestingly, allergic pregnant women have lower plasma sHLA-G levels than non-allergic women during the 3rd trimester of pregnancy and at delivery. Finally, in allergic patients with atopic dermatitis HLA-G molecules are expressed by T cells, monocytes-macrophages and Langerhans cells infiltrating the dermis. Although at present is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are specifically expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.

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The role of IgE, IgG, and IgA in tolerance, sensitization, and targeted treatment of allergic disease

10.22541/au.161696538.85380953/v2 ◽

2021 ◽

Author(s):

Mohamed Shamji ◽

Rudolf Valenta ◽

Theodore Jardetzky ◽

Valerie Verhasselt ◽

Stephen Durham ◽

...

Keyword(s):

Immunoglobulin E ◽

Allergic Sensitization ◽

Passive Immunization ◽

Allergic Inflammation ◽

Allergic Diseases ◽

Immediate Release ◽

Specific Ige ◽

Allergen Specific Immunotherapy ◽

Effector Cells ◽

Iga Antibodies

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. In genetically-predisposed subjects exposure to minute quantities of allergens leads to the production of IgE antibodies which is termed allergic sensitization and mainly occurs in early childhood. Allergen-specific IgE then binds to the high (FcRI) and low affinity receptors (FcRII, also called CD23) for IgE on effector cells and antigen-presenting cells, respectively. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared to IgE, and do not efficiently interfere with allergen-induced inflammation. However IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mastcells and basophils. Here we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.

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The role of IgE, IgG, and IgA in tolerance, sensitization, and targeted treatment of allergic disease

10.22541/au.161696538.85380953/v1 ◽

2021 ◽

Author(s):

Mohamed Shamji ◽

Rudolf Valenta ◽

Theodore Jardetzky ◽

Valerie Verhasselt ◽

Stephen Durham ◽

...

Keyword(s):

Immunoglobulin E ◽

Allergic Sensitization ◽

Passive Immunization ◽

Allergic Inflammation ◽

Allergic Diseases ◽

Immediate Release ◽

Specific Ige ◽

Allergen Specific Immunotherapy ◽

Effector Cells ◽

Iga Antibodies

Immunoglobulin E (IgE)-mediated allergy is the most common hypersensitivity disease affecting more than 30% of the population. In genetically-predisposed subjects exposure to minute quantities of allergens leads to the production of IgE antibodies which is termed allergic sensitization and mainly occurs in early childhood. Allergen-specific IgE then binds to the high (FcRI) and low affinity receptors (FcRII, also called CD23) for IgE on effector cells and antigen-presenting cells, respectively. Subsequent and repeated allergen exposure increases allergen-specific IgE levels and, by receptor cross-linking, triggers immediate release of inflammatory mediators from mast cells and basophils whereas IgE-facilitated allergen presentation perpetuates T cell-mediated allergic inflammation. Due to engagement of receptors which are highly selective for IgE even tiny amounts of allergens can induce massive inflammation. Naturally occurring allergen-specific IgG and IgA antibodies usually recognize different epitopes on allergens compared to IgE, and do not efficiently interfere with allergen-induced inflammation. However IgG and IgA antibodies to these important IgE epitopes can be induced by allergen-specific immunotherapy or by passive immunization. These will lead to competition with IgE for binding with the allergen and prevent allergic responses. Similarly, anti-IgE treatment does the same by preventing IgE from binding to its receptor on mastcells and basophils. Here we review the complex interplay of allergen-specific IgE, IgG and IgA and the corresponding cell receptors in allergic diseases and its relevance for diagnosis, treatment and prevention of allergy.

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Immunotheraphy in Allergic Diseases

Current Pharmaceutical Design ◽

10.2174/1381612824666180116094048 ◽

2018 ◽

Vol 24 (11) ◽

pp. 1174-1194

Author(s):

Albert Roger ◽

Maria Basagana ◽

Aina Teniente-Serra ◽

Nathalie Depreux ◽

Yanina Jurgens ◽

...

Keyword(s):

Specific Immunotherapy ◽

Allergic Diseases ◽

Specific Ige ◽

World Population ◽

Allergen Specific Immunotherapy ◽

Routes Of Administration ◽

Disease Modifying Therapy ◽

History Of ◽

Ige Mediated ◽

Special Case

The prevalence of allergic diseases is increasing worldwide. It is estimated that more than 30% of the world population is now affected by one or more allergic conditions and a high proportion of this increase is in young people. The diagnosis of allergy is dependent on a history of symptoms on exposure to an allergen together with the detection of allergen-specific IgE. Accurate diagnosis of allergies opens up therapeutic options. Allergen specific immunotherapy is the only successful disease-modifying therapy for IgE-mediated allergic diseases. New therapeutic strategies have been developed or are currently under clinical trials. Besides new routes of administration, new types of allergens are being developed. The use of adjuvants may amplify the immune response towards tolerance to the antigens. In this review, we analyze different antigen-specific immunotherapies according to administration route, type of antigens and adjuvants, and we address the special case of food allergy.

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Allergic Inflammation Caused by Dimerized Translationally Controlled Tumor Protein is Attenuated by Cardamonin

Frontiers in Pharmacology ◽

10.3389/fphar.2021.765521 ◽

2021 ◽

Vol 12 ◽

Author(s):

Haejun Pyun ◽

Joo-Won Nam ◽

Hyunsoo Cho ◽

Jiyoung Park ◽

Eun Kyoung Seo ◽

...

Keyword(s):

Bronchoalveolar Lavage Fluid ◽

Allergic Inflammation ◽

Inflammatory Cells ◽

Allergic Diseases ◽

Lavage Fluid ◽

Specific Ige ◽

Translationally Controlled Tumor Protein ◽

Dimeric Form ◽

Allergic Mouse ◽

Inflammatory Effect

We demonstrated in our previous reports that dimeric form of translationally controlled tumor protein (dTCTP) initiates a variety of allergic phenomena. In the present study, we examined whether and how dTCTP’s role in allergic inflammation can be modulated or negated. The possible potential of cardamonin as an anti-allergic agent was assessed by ELISA using BEAS-2B cells and OVA-challenged allergic mouse model. The interaction between cardamonin and dTCTP was confirmed by SPR assay. Cardamonin was found to reduce the secretion of IL-8 caused by dTCTP in BEAS-2B cells by interacting with dTCTP. This interaction between dTCTP and cardamonin was confirmed through kinetic analysis (KD = 4.72 ± 0.07 μM). Also, cardamonin reduced the migration of various inflammatory cells in the bronchoalveolar lavage fluid (BALF), inhibited OVA specific IgE secretion and bronchial remodeling. In addition, cardamonin was observed to have an anti-allergic response by inhibiting the activity of NF-κB. Cardamonin exerts anti-allergic anti-inflammatory effect by inhibiting dTCTP, suggesting that it may be useful in the therapy of allergic diseases.

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The role of barrier function of mucous membranes in allergic diseases and sublingual allergen-specific immunotherapy

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2017-2-32-46 ◽

2017 ◽

Vol 16 (2) ◽

pp. 32-46

Author(s):

Oksana M. Kurbacheva ◽

Miramgul E. Amanturlieva

Keyword(s):

Barrier Function ◽

Specific Immunotherapy ◽

Allergic Diseases ◽

Allergen Specific Immunotherapy ◽

Mucous Membranes

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Circulating Conventional and Plasmacytoid Dendritic Cell Subsets Display Distinct Kinetics duringIn VivoRepeated Allergen Skin Challenges in Atopic Subjects

BioMed Research International ◽

10.1155/2014/231036 ◽

2014 ◽

Vol 2014 ◽

pp. 1-14 ◽

Cited By ~ 10

Author(s):

Stelios Vittorakis ◽

Konstantinos Samitas ◽

Sofia Tousa ◽

Eleftherios Zervas ◽

Maria Aggelakopoulou ◽

...

Keyword(s):

Tissue Repair ◽

Plasmacytoid Dendritic Cell ◽

Allergic Inflammation ◽

Allergen Challenge ◽

Allergic Diseases ◽

Activin A ◽

Receptor Expression ◽

Expression Ratio

Upon allergen challenge, DC subsets are recruited to target sites under the influence of chemotactic agents; however, details pertinent to their trafficking remain largely unknown. We investigated the kinetic profiles of blood and skin-infiltrating DC subsets in twelve atopic subjects receiving six weekly intradermal allergen and diluent injections. The role of activin-A, a cytokine induced in allergic and tissue repair processes, on the chemotactic profiles of DC subsets was also examined. Plasmacytoid (pDCs) and conventional DCs (cDCs) were evaluated at various time-points in the blood and skin.In situactivin-A expression was assessed in the skin and its effects on chemokine receptor expression of isolated cDCs were investigated. Blood pDCs were reduced 1 h after challenge, while cDCs decreased gradually within 24 h. Skin cDCs increased significantly 24 h after the first challenge, inversely correlating with blood cDCs. Activin-A in the skin increased 24 h after the first allergen challenge and correlated with infiltrating cDCs. Activin-A increased the CCR10/CCR4 expression ratio in cultured human cDCs. DC subsets demonstrate distinct kinetic profiles in the blood and skin especially during acute allergic inflammation, pointing to disparate roles depending on each phase of the inflammatory response. The effects of activin-A on modulating the chemotactic profile of cDCs suggest it may be a plausible therapeutic target for allergic diseases.

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Sphingolipids: A Potential Molecular Approach to Treat Allergic Inflammation

Journal of Allergy ◽

10.1155/2012/154174 ◽

2012 ◽

Vol 2012 ◽

pp. 1-14 ◽

Cited By ~ 3

Author(s):

Wai Y. Sun ◽

Claudine S. Bonder

Keyword(s):

Current Knowledge ◽

Financial Burden ◽

Late Phase ◽

Allergic Inflammation ◽

Allergic Diseases ◽

Racial Groups ◽

Worldwide Population ◽

Life Threatening

Allergic inflammation is an immune response to foreign antigens, which begins within minutes of exposure to the allergen followed by a late phase leading to chronic inflammation. Prolonged allergic inflammation manifests in diseases such as urticaria and rhino-conjunctivitis, as well as chronic asthma and life-threatening anaphylaxis. The prevalence of allergic diseases is profound with 25% of the worldwide population affected and a rising trend across all ages, gender, and racial groups. The identification and avoidance of allergens can manage this disease, but this is not always possible with triggers being common foods, prevalent air-borne particles and only extremely low levels of allergen exposure required for sensitization. Patients who are sensitive to multiple allergens require prophylactic and symptomatic treatments. Current treatments are often suboptimal and associated with adverse effects, such as the interruption of cognition, sleep cycles, and endocrine homeostasis, all of which affect quality of life and are a financial burden to society. Clearly, a better therapeutic approach for allergic diseases is required. Herein, we review the current knowledge of allergic inflammation and discuss the role of sphingolipids as potential targets to regulate inflammatory development in vivo and in humans. We also discuss the benefits and risks of using sphingolipid inhibitors.

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The Biologic Role of Interleukin-8: Functional Analysis and Expression of CXCR1 and CXCR2 on Human Eosinophils

Blood ◽

10.1182/blood.v93.2.694.402k31_694_702 ◽

1999 ◽

Vol 93 (2) ◽

pp. 694-702

Author(s):

Holger Petering ◽

Otto Götze ◽

Daniela Kimmig ◽

Regina Smolarski ◽

Alexander Kapp ◽

...

Keyword(s):

Allergic Inflammation ◽

Allergic Diseases ◽

Interleukin 8 ◽

Cytokine Activation ◽

Cc Chemokines ◽

Eosinophil Granulocytes ◽

In Vitro Effects

Chemokines play an important role in attracting granulocytes into sites of inflammation. Two chemokine subfamilies differ in their biologic activity for different granulocyte subsets. Whereas CXC chemokines such as interleukin-8 (IL-8) activate predominantly neutrophils, CC chemokines such as RANTES and eotaxin activate predominantly eosinophils. However, controversial results have been published in the past regarding the biologic role of IL-8 in eosinophil activation, particularly in allergic diseases. In this study, we investigated the functional evidence and expression of both IL-8 receptors, CXCR1 and CXCR2, on highly purified human eosinophils. In the first set of experiments, a chemotaxis assay was performed showing that IL-8 did not induce chemotaxis of eosinophils. In addition, and in contrast to neutrophils and lymphocytes, IL-8 did not induce a rapid and transient release of cytosolic free Ca2+([Ca2+]i) in eosinophils, even after preincubation with TH1- and TH2-like cytokines. To investigate whether neutrophil contamination might be responsible for the reported IL-8 effects on eosinophils, neutrophils were added to highly purified eosinophils from the same donor in different concentrations. Interestingly, as little as 5% of neutrophil contamination was sufficient to induce an increase of [Ca2+]iafter stimulation with IL-8. Flow cytometry experiments with monoclonal antibodies against both IL-8 receptors demonstrated no expression of CXCR1 and CXCR2 on eosinophils before or after cytokine activation. Reverse transcriptase-polymerase chain reaction experiments showed that eosinophils, in contrast to neutrophils and lymphocytes, did not express mRNA for CXCR1 and CXCR2. In summary, this study clearly demonstrates that CXCR1 and CXCR2 are not expressed on human eosinophils, even after priming with different bioactive cytokines. Because the CXC chemokine IL-8 did not induce in vitro effects on human eosinophils, IL-8 may also not contribute in vivo to the influx of eosinophil granulocytes into sites of allergic inflammation. Our results suggest that CC chemokines such as eotaxin, eotaxin-2, and MCP-4 are predominant for the activation of eosinophils.

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The atopic desease development in infants and preschool children in Lesnoy town of Sverdlovsk region

Rossiiskii Allergologicheskii ZHurnal ◽

10.36691/rja467 ◽

2015 ◽

Vol 12 (2) ◽

pp. 59-63

Author(s):

N A Volkova ◽

I A Tuzankina ◽

V N Shershnev

Keyword(s):

Preschool Children ◽

Clinical Symptoms ◽

Allergic Diseases ◽

Specific Ige ◽

Atopic Diseases ◽

Different Types ◽

Specific Ige Antibodies ◽

Airborne Allergens

The aim of study. To determine the structure of atopic diseases and characterization of different allergens in their progression in infants and preschool children in Lesnoy town. Material and methods. We studied a spectrum of allergen-specific IgE antibodies in children’s blood with different allergic diseases. Comparative analysis of the results was conducted with methods of mathematical statistics. Results. Our data demonstrate the different stages of formation of atopic diseases in children. We revealed that clinical symptoms of atopic diseases and relevance of allergens were changing gradually as children were getting older. Our results showed that the role of nutrition allergens is reduced while airborne allergens came to the fore. Conclusion. Formation and progression of atopic diseases are determined by various allergens. The temporary relevance of different types of allergens indicates a diversity of multivalent sensibilization during affection of the «shock» organ; the result of this phenomenon appears as atopic march. Detection the relevant causative allergens is important for prevention of progression of allergic diseases.

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