Intestinal B Cell-Activating Factor and Food Hypersensitivity
Intestinal B Cell-Activating Factor and Food Hypersensitivity
Background Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose.
Aim To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease.
Methods Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid.
Results B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE.
Conclusions The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions.
Food hypersensitivity is an 'umbrella term' which refers to all types of adverse reactions to food, both allergic and non-allergic (food intolerance) reactions. While food allergy involves immunological mechanisms, non-allergic food hypersensitivity does not. Food allergy can be IgE-mediated (type I) or non-IgE-mediated (type III or IV). Type I hypersensitivity is characterized by an immediate reaction shortly after contact with the allergen (within minutes – up to 2 h). Here, high-affinity IgE receptor (Fc€RI)-bearing mast cells and basophils are key effector cells. After cross-linking Fc bearing mast cells and RI receptors by antigen-specific IgE molecules, mast cells and basophils release various mediators such as histamine, heparin, leucotriens, prostaglandins and cytokines. Delayed-type hypersensitivity reactions occur 2–24 h after allergen exposure without involvement of IgE and can be both immune and non-immune-mediated.
B cell-activating factor (BAFF) is a member of the tumour necrosis factor (TNF) superfamily (TNFSF13B) and an important regulator of peripheral B cell survival, maturation and immunoglobulin class-switch recombination (CSR). CSR is a biological mechanism by which activated B cells (plasma cells) change their antibody production from one isotype to another, for example, from IgM to IgG. Naive mature B cells produce both IgM and IgD, which contain the first two heavy chain segments of the immunoglobulins. To make a new isotype of antibody, CSR requires two signals. The first signal normally comes through T cell cytokines (IL-4, IL-10, IL-13 and TGF-β), while the second is delivered by engagement of CD40 on B cells. In addition, BAFF impact is involved in this process by one of its specific receptors, called TACI. Despite the fact that CSR is generally restricted to lymphoid organs, previous studies show that local immunoglobulin CSR and IgE production also occur in the nasal and airway mucosa of patients with allergic asthma and allergic rhinitis, as well as in the oesophageal mucosa of patients with eosinophilic oesophagitis.
B cell-activating factor is mainly produced and secreted not only by myeloid cells (macrophages, monocytes and dendritic cells) but also by non lymphoid cell types (salivary gland epithelial cells, astrocytes and fibroblast-like synoviocytes) and epithelial cells including bronchial and nasal epithelial cells. The biological role of BAFF is mediated through the specific receptors; two high-affinity receptors, BAFF receptor (BAFF-R) and transmembrane activator-calcium modulator and cyclophilin ligand interactor (TACI), and a low-affinity receptor, B cell maturation antigen (BCMA). BAFF-R present on the surface of effector T cells is a potent regulator of mature B-cell survival and IgE production by BAFF, whereas TACI on surfaces of B cells is critical for CSR.
High levels of BAFF have been reported in patients with allergic disease (asthma) and autoimmune diseases such as systemic lupus erythematosus, Sjögren`s syndrome, rheumatoid arthritis, systemic sclerosis, mixed cryoglobulinaemia, myasthenia gravis and coeliac disease. Overexpression of BAFF in animal models leads to B-cell hyperplasia, lymphoproliferation, hypergammaglobulinaemia and symptoms of autoimmunity. Conversely, BAFF-deficient animals exhibit defects in peripheral B-cell maturation and decreased levels of immunoglobulins. Recently, BAFF has emerged also as an important regulator of T-cell function, particularly during T-cell-mediated reactions.
Patients with self-reported food hypersensitivity complain of a wide range of unexplained somatic symptoms related to the intake of food. Often, the patients feel quite ill with considerably impaired quality of life. The condition is common. In the general population, approximately 1 of 5 (20%) adults reports food-related hypersensitivity reactions. Food allergy is confirmed in only 3–5% and the confirmed reactions are usually IgE-mediated. Non-IgE-mediated reactions are seldom recognized. Thus, in most cases, the cause of self-reported food hypersensitivity remains elusive. A possible role of BAFF has not yet been investigated in these patients. In the present explorative study, we therefore wanted to investigate whether BAFF could be determined in blood and gut lavage fluid in patients with self-reported food hypersensitivity. Retrospectively, we investigated the relationship between BAFF and atopic disease in the patients.
Abstract and Introduction
Abstract
Background Medically confirmed hypersensitivity reactions to food are usually IgE-mediated. Non-IgE-mediated reactions are not only seldom recognized but also more difficult to diagnose.
Aim To examine B cell-activating factor (BAFF) in serum and gut lavage fluid of patients with self-reported food hypersensitivity, and to study its relationship to atopic disease.
Methods Gut lavage fluid was obtained from 60 and serum from another 17 patients with self-reported food hypersensitivity. Twenty healthy volunteers served as controls, gut lavage fluid was obtained in all, serum from 11 of 20. The patients were divided into atopic and non-atopic subgroups. BAFF was measured by ELISA in both serum and gut lavage fluid.
Results B cell-activating factor levels in serum and gut lavage fluid were significantly higher in patients than in controls (P < 0.03 and P < 0.002 respectively). Non-atopic patients had significantly higher levels of BAFF in serum than both atopic patients (P < 0.05) and controls (P < 0.05). There was no significant correlation between serum levels of BAFF and IgE.
Conclusions The results suggest that BAFF might be a new mediating mechanism in food hypersensitivity reactions. Significantly higher levels in non-atopic compared with atopic patients, and no correlation between BAFF and IgE, suggest that BAFF might be involved particularly in non-IgE-mediated reactions.
Introduction
Food hypersensitivity is an 'umbrella term' which refers to all types of adverse reactions to food, both allergic and non-allergic (food intolerance) reactions. While food allergy involves immunological mechanisms, non-allergic food hypersensitivity does not. Food allergy can be IgE-mediated (type I) or non-IgE-mediated (type III or IV). Type I hypersensitivity is characterized by an immediate reaction shortly after contact with the allergen (within minutes – up to 2 h). Here, high-affinity IgE receptor (Fc€RI)-bearing mast cells and basophils are key effector cells. After cross-linking Fc bearing mast cells and RI receptors by antigen-specific IgE molecules, mast cells and basophils release various mediators such as histamine, heparin, leucotriens, prostaglandins and cytokines. Delayed-type hypersensitivity reactions occur 2–24 h after allergen exposure without involvement of IgE and can be both immune and non-immune-mediated.
B cell-activating factor (BAFF) is a member of the tumour necrosis factor (TNF) superfamily (TNFSF13B) and an important regulator of peripheral B cell survival, maturation and immunoglobulin class-switch recombination (CSR). CSR is a biological mechanism by which activated B cells (plasma cells) change their antibody production from one isotype to another, for example, from IgM to IgG. Naive mature B cells produce both IgM and IgD, which contain the first two heavy chain segments of the immunoglobulins. To make a new isotype of antibody, CSR requires two signals. The first signal normally comes through T cell cytokines (IL-4, IL-10, IL-13 and TGF-β), while the second is delivered by engagement of CD40 on B cells. In addition, BAFF impact is involved in this process by one of its specific receptors, called TACI. Despite the fact that CSR is generally restricted to lymphoid organs, previous studies show that local immunoglobulin CSR and IgE production also occur in the nasal and airway mucosa of patients with allergic asthma and allergic rhinitis, as well as in the oesophageal mucosa of patients with eosinophilic oesophagitis.
B cell-activating factor is mainly produced and secreted not only by myeloid cells (macrophages, monocytes and dendritic cells) but also by non lymphoid cell types (salivary gland epithelial cells, astrocytes and fibroblast-like synoviocytes) and epithelial cells including bronchial and nasal epithelial cells. The biological role of BAFF is mediated through the specific receptors; two high-affinity receptors, BAFF receptor (BAFF-R) and transmembrane activator-calcium modulator and cyclophilin ligand interactor (TACI), and a low-affinity receptor, B cell maturation antigen (BCMA). BAFF-R present on the surface of effector T cells is a potent regulator of mature B-cell survival and IgE production by BAFF, whereas TACI on surfaces of B cells is critical for CSR.
High levels of BAFF have been reported in patients with allergic disease (asthma) and autoimmune diseases such as systemic lupus erythematosus, Sjögren`s syndrome, rheumatoid arthritis, systemic sclerosis, mixed cryoglobulinaemia, myasthenia gravis and coeliac disease. Overexpression of BAFF in animal models leads to B-cell hyperplasia, lymphoproliferation, hypergammaglobulinaemia and symptoms of autoimmunity. Conversely, BAFF-deficient animals exhibit defects in peripheral B-cell maturation and decreased levels of immunoglobulins. Recently, BAFF has emerged also as an important regulator of T-cell function, particularly during T-cell-mediated reactions.
Patients with self-reported food hypersensitivity complain of a wide range of unexplained somatic symptoms related to the intake of food. Often, the patients feel quite ill with considerably impaired quality of life. The condition is common. In the general population, approximately 1 of 5 (20%) adults reports food-related hypersensitivity reactions. Food allergy is confirmed in only 3–5% and the confirmed reactions are usually IgE-mediated. Non-IgE-mediated reactions are seldom recognized. Thus, in most cases, the cause of self-reported food hypersensitivity remains elusive. A possible role of BAFF has not yet been investigated in these patients. In the present explorative study, we therefore wanted to investigate whether BAFF could be determined in blood and gut lavage fluid in patients with self-reported food hypersensitivity. Retrospectively, we investigated the relationship between BAFF and atopic disease in the patients.
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