Low-affinity IgE receptor (FcεRII)-mediated activation of human monocytes by both monomeric IgE and IgE/anti-IgE immune complex (original) (raw)
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IgE antibody-specific activity in human allergic disease
Immunologic Research, 2010
IgE antibody concentration, affinity, clonality and specific activity (also known as the allergen-specific IgE to total IgE ratio) influence the translation of IgE responses into clinically evident allergic symptoms following allergen exposure. Reported IgE-specific activity levels [3-4% place allergic individuals undergoing anti-IgE (Omalizumab Ò ) therapy at a disadvantage for poor resolution of their allergy symptoms following manufacturer's recommended dosing schemes. We investigated the hypothesis that the specific activity of the IgE antibody response is highly variable with respect to age, allergen specificity and an individual's total serum IgE level. Second, we investigated whether the IgE-specific activity level influences the extent and rate of loss of effector cell mediator release. IgE-specific activity distributions were plotted against age, allergen specificity and total serum IgE using 18,950 paired total IgE and allergen-specific IgE antibody data obtained from the analysis of sera from 3,614 allergic subjects and covering 182 allergen specificities. The fraction of specific IgE antibody of the total serum IgE was dependent on age of the individual, epitope specificity (clonality) and total serum IgE. The youngest group of allergic individuals with the lowest total serum IgE levels tended to have the highest allergen-specific IgE to total IgE ratios. Hymenoptera venom (54%), peanut (33%) and milk (27%) were the three allergen specificities that elicited the highest frequency of IgE-specific activities [4% among sensitized individuals. A prospective double-blind, placebo-controlled clinical study involving anti-IgE treatment of cat-allergic subjects showed IgE-specific activity was remarkably constant over the 16-week course of treatment, despite the up to 8-fold rise in total serum IgE following repetitive Omalizumab Ò administration. Changes in specific and total IgE levels paralleled each other in patients receiving anti-IgE therapy. The fastest rate of reduction in cat allergen-induced basophil histamine release following anti-IgE therapy was observed when the cat-specific IgE to total IgE ratio was \2.5%. This reflected the more rapid loss of surface cat-specific IgE antibody with anti-IgE therapy in allergic individuals who displayed a more diverse IgE antibody repertoire. We conclude that IgE-specific activity is an age-, IgE heterogeneity-and total serum IgE-dependent variable that influences the magnitude of effector cell mediator release, and by inference, ultimate allergic symptom induction.
Journal of Clinical Pathology-molecular Pathology, 1995
Aims-To investigate the ability of circulating IgG autoanti-IgE antibodies from atopic rhinitis patients to block the binding of IgE to its low affinity receptor (FcERII), also termed CD23. Methods-This involved the use of a well validated flow cytometric method to detect inhibition of FITC labelled IgE binding to human B cells expressing CD23 (RPMI 8866 cell line). Results-Taking inhibition values greater than 20% as being significant, 15 out of 20 IgG anti-IgE containing sera inhibited the binding of IgE-FITC to the RPMI 8866 cells. The inhibitory effect was recoverable in the IgG fraction of serum, but was not related to the titre of either IgGi anti-IgE or IgG4 anti-IgE, thus suggesting that it might be related to epitope specificity. No such inhibition was demonstrable with rheumatoid sera containing autoanti-IgG (that is, rheumatoid factor), but lacking autoanti-IgE. Conclusions-The capacity of anti-IgE to block the binding of IgE to CD23 has important implications, particularly in terms of upregulation of IgE synthesis and the consequent perpetuation of the inflammatory response.
Cytokine regulation of low-affinity IgE receptor (CD23) on monocytes from asthmatic subjects
Clinical & Experimental Immunology, 2008
The regulation of CD23 expression (FcERII) by cytokines on monocytes from normal subjects, asymptomatic and acute asthmatics was investigated. CD23 was weakly expressed on cells from controls, but was significantly enhanced in the two groups of asthmatics. The addition of IL-4 on monocytes induced an increase of CD23 expression in cells from controls and asthmatics. Interferon-gamma (IFN-y) did not modulate CD23 expression in asthmatics or control subjects, while high doses of IL-6 (2000 U/ml) enhanced CD23 expression on cells from asthmatics or controls. In vitro stimulation of monocytes with Timothy grass pollen allergen did not enhance CD23 receptor in asthmatics with a positive skin test to this pollen. We speculate that CD23 expression in asthmatics is markedly enhanced by Th2-dependent cytokines, such as IL-4 and IL-6. Thus, the regulation of Th2 cell activation by anti-cytokine therapy could have an important effect on the down-regulation of CD23 on monocytes, and in shifting a Th2 subpopulation into a Thl subpopulation by blocking Th2-dependent cytokines.
Demonstration of intracytoplasmic IgE in circulating lymphocytes of allergic individuals
Cellular Immunology, 1985
Cells containing intracytoplasmic IgE (IC IgE) were demonstrated in the peripheral blood mononuclear cells of atopic individuals by means of indirect immunofluorescence, employing mouse monoclonal anti-human IgE antibody. IC IgE-positive cells are lowdensity B cells as shown by centrifugation on discontinuous bovine serum albumin density gradient and by their reactivity with B, monoclonal antibody specific to B lymphocytes, respectively. Further characterization of these cells by means of a rosette assay employing anti-I&coupled bovine erythrocytes indicated that these ceils were surface IgP (sIgE) positive and sIgM negative. The data strongly suggest that activated IgP B cells are circulating in the blood of allergic individuals.
IgE-mediated allergic responses (PP-021)
International Immunology, 2010
We previously reported that minocycline treatment of allergic asthmatic patients had oral steroid sparing effects and improved their clinical status, suppressed in vitro induction of IgE responses by their PBMC, and suppressed mast-cell mediated cutaneous late phase responses. The effect of minocycline on human or animal IgE responses in vivo has not been studied. Allergic asthmatics (serum IgE: 505 + 535 IU/ml) were given minocycline (150 mg po to 250 mg po BID) as add-on therapy to standard care for up to 10 months; control subjects (IgE: 405 + 472 IU/ml) received standard (n ¼ 6/group). Serum immunoglobulin (IgM, IgG, IgE, IgA) levels were determined monthly (Nephelometry, Unicap Total IgE Fluoroenzyme immunoassay). BALB/c mice (n ¼ 6/group) were injected i.p. with BPO 14-KLH in alum on days 0, 21 and 42, fed with minocycline or doxycycline (10-100 mg/kg) on day 44, and numbers of BPO-specific IgG 1 , IgE and IgA antibody forming cell (AFC) in mesenteric LN and spleen, and serum immunoglobulin levels determined on days 46-70 (ELISPOTassay, ELISA). The ability to suppress in vitro induction of murine memory IgE responses also was investigated. Minocycline strongly suppressed serum IgE levels of allergic asthmatics (9%/ month) (p ¼ 0.012). Minocycline (and doxycycline) also strongly suppressed peak murine IgE AFC and serum IgE responses (.95, 75%, respectively), and in vitro induction of memory IgE responses by murine mesenteric LN and spleen cells (.95%). Tetracycline suppression of all human and murine IgE responses was IgE isotype specific. Suppression of murine IgE responses in vivo was dose dependent and lasted 5-7 days.
The cellular lesion responsible for exaggerated IgE synthesis accompanying allergic breakthrough
Cellular Immunology, 1989
Appropriate levels of IgE are maintained by a cellular and molecular network composed of (1) a suppressive, Ly-l+, CD4+ T cell-dependent arm that is activated by inappropriate high levels of IgE and (2) an enhancing, CD8+ T cell-dependent arm that controls this suppression in a feedback regulatory manner. Ly-l+ T cells also function to counterbalance (inhibit) the activity of these latter CD8+ T cells. It has been previously shown that Ly-1 + T cells can reverse low-dose irradiation-induced enhancement of IgE antibody responses (i.e., allergic breakthrough). We have analyzed lymphocytes isolated from mice subjected to low-dose irradiation to determine which component of this network is defective in such animals. Stimulation of normal lymphocytes with IgE in vitro resulted in the release of lymphokines that suppress IgE antibody responses. In contrast, similar stimulation of lymphocytes from irradiated mice did not elicit secretion of such suppressive lymphokines, unless the cells were depleted of CDS+ T cells or reconstituted with normal Ly-1 + T cells. Because Ly-1 + T cells of irradiated mice could not reconstitute the response, we conclude that this functional subset of CD4+ T cells, which normally controls CD8+ T cell activity in this network, is defective in animals that exhibit irradiation-induced allergic breakthrough. o 1989 Academic press, IN.