The detection of autoantibodies to IgE in plasma of individuals infected with hookworm (Necator americanus) and the demonstration of a predominant IgG1 anti‐lgE autoantibody response

Abstract

In this study we have demonstrated significantly elevated levels of circulating IgG autoanti-IgE antibody in hookworm infected individuals from Kebasob village on Karkar Island, Papua New Guinea. Although anti-IgE activity was demonstrable in IgG1, IgG3 and IgG4, IgG1 was by far the most important subclass of IgG anti-IgE in terms of frequency of detection (34/39; 87.2%) and magnitude of increase (P = 0.0000); with IgG3 (16/39; 41.0%) and IgG4 (15/39; 38.5%) antibodies being considerably less prevalent. Plasma levels of IgG1 anti-IgE (P = 0.0019) and IgG3 anti-IgE (P = 0.0034) showed significant correlations with total IgE concentrations, but not with IgE specific to excretory-secretory worm products; thus suggesting that anti-IgE synthesis is more related to polyclonal hyper IgE production than to antigen-specific IgE stimulation. No correlation was seen between IgG subclass anti-IgE levels and faecal egg counts or worm burden. Given that our data failed to show a negative or a positive correlation between anti-IgE and the degree of infection with hookworm, it is tempting to speculate that the main role of autoanti-IgE is to provide the host with protection against immune complex- and IgE-mediated hypersensitivity reactions to parasitic antigens.

Hookworm virulence factors: making the most of the host

“…The levels of sCD23 in plasma samples from hookworm-infected individuals are significantly elevated and negatively correlated with both age and circulating levels of total IgE, particularly in the young. Therefore, the production of excess, non-parasite specific IgE could inhibit specific effector mechanisms by blocking Fcε receptors with irrelevant antibody and auto-antibodies [3,66,67]. The lack of a correlation between total and parasite-specific IgE is not unusual, and reflects the fact that a disproportionate and variable amount of IgE in necatoriasis is polyclonal and not necessarily specific for hookworm.…”

In vitro basophil histamine‐releasing activity of circulating IgG1 and IgG4 autoanti‐IgE antibodies from asthma patients and the demonstration that anti‐IgE modulates allergen‐induced basophil activation

“…Elevated blood levels of IgG anti-lgE are detectable in individuals exhibiting enhanced IgE production, namely those with allergic conditions (e.g. asthma) [1][2][3][4] and parasite (hookworm and schistosomes) infections [5]. Our studies of human IgG anti-lgE have mostly focused on allergic asthma [3][4][5][6][7], where IgG anti-lgE is highly prevalent [1][2][3][4].…”

Autoanti-IgE antibodies in patients with allergic and idiopathic rhinitis

“…The concept of blocking antibodies in allergic reactions was first introduced in 1935, 19 but it was only when detailed assays became available that naturally occurring anti‐IgE was identified 20 . IgG autoanti‐IgE antibodies are now known to be present in the serum of patients with atopic disorders such as asthma and urticaria 10,12 , 21 and also in helminth infections 18 . Although their exact role is uncertain, 14,16 , 22 it is known that high levels of these antibodies at birth protect children from the development of atopic disease 23 .…”

“…The IgE protein used to coat the ELISA microtitre plate wells was isolated from the plasma of an IgE myeloma patient (WT; lambda light chain). The IgE protein was isolated in pure form by precipitation and chromatography to remove contaminants 18 . Serum samples were diluted 1:5 and incubated in IgE‐coated (2 μg/ml) microtitre wells (Dynatech Laboratories, Sussex); bound immunoglobulin was detected using mouse monoclonal anti‐human IgG1 and IgG4 (Oxoid, Basingstoke).…”