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Development, recognition and significance of lgG antibodies in allergic sensitisation and adverse reactions to peanut
Project Code: T07036
Regional Immunology Department, St Mary's Hospital
Patients with specific IgE antibodies to peanut are at risk of experiencing an adverse reaction if they encounter either peanut or peanut containing products. In addition to the low levels of IgE antibodies responsible for these reactions, much higher levels of IgG antibodies to peanut are also detected in patients’ sera.
The presence of high levels of specific IgG antibodies could affect the binding of allergen to IgE, and in turn influence the severity of the allergic reaction in patients who are clinically sensitive to peanut.
The possibility of competition between IgG and IgE antibodies can only arise if both forms of antibody are able to bind to the same sites on the peanut allergen. Binding to separate sites would make the antibodies independent of each other.
Levels of peanut specific IgG and IgE antibody were compared between patients who had consistently reported “mild” reactions when exposed to peanut and those who had experienced more “severe” reactions.
Paired samples were analysed to investigate if peanut and Ara h2 antibody levels are stable or change following an adverse reaction to peanut. The time interval investigated was around 1 year.
The specificity of IgG and IgE for the linear binding sites present on a major peanut allergen was compared using commercially synthesized overlapping peptides.
Lastly, the development of specific antibodies to Ara h2 was retrospectively analysed for a small number of children less than ten years of age. The aim was to assess if changes in IgE peanut specific antibodies are paralleled by changes in other peanut specific antibody classes.
For the cohort of patients studied, median peanut specific IgE levels were significantly higher in patients who reported severe clinical reactions following peanut exposure. In contrast, median levels of specific IgG were found to be indistinguishable between those with “mild” or “severe” reactions.
The same patients with “mild” and “severe” symptoms were analysed for differences between the individual IgG subclasses. No significant differences were detected in either the IgG1 or IgG3 subclasses. In contrast, peanut specific IgG4 antibodies were significantly higher in the patients classified as severe compared to the patients with mild reactions. IgG2 was of borderline significance between the two groups.
These results translate into a higher specific IgG/IgE ratio in patients with mild symptoms due to the low IgE levels in this group of patients. Overall, the mean ratio of IgG/ IgE was threefold higher in the group with mild symptoms.
There appears to be a weak although significant positive correlation between the levels of peanut-specific IgG and peanut-specific IgE. Although individual patients show exceptions to this trend.
No significant association between the magnitude of the skin prick test response and the level of peanut specific IgG was detected for the patients analysed. However, the median value for peanut specific IgG was higher at 8.3mg/l in patients with a strong skin prick test response compared to those with weak skin prick test response at 6.1mg/l.
Similarly, if the magnitude of the skin prick test response was compared to the ratio of peanut specific IgG/IgE for all the patients no association was apparent. In contrast, for the group of patients who were susceptible to severe reactions, the specific IgG/IgE ratio was significantly higher when the skin prick test response proved weak.
Median specific IgG levels significantly decreased in the second of the paired samples obtained “distant” from the adverse reaction. This occurred in two particular subclasses IgG1 and IgG2 whereas IgG3 and IgG4 were unchanged. It is possible that the change in specific IgG is a result of improved dietary compliance following an adverse reaction.
No difference in median IgE levels to peanut was observed for the same paired samples. This suggests that the specific IgE response may be retained for longer. The mechanism responsible for the separate control of IgG and IgE antibody levels is unclear.
The Arah2 peptide studies confirm that competition between specific IgG and IgE antibodies is possible, as the IgE binding epitopes extensively overlap with the IgG binding epitopes. Some sites were identified that exclusively bound IgG or IgE. Other sites were recognized by both IgE and IgG antibodies. Potentially the latter may be of importance in the targeting of monoclonal antibodies that do not interfere with IgE binding to the allergen.
A monoclonal antibody raised against Ara h2 strongly bound to the sequence PYSPSQDRYS(PS), which in part is also recognised by patient’s sera.
The retrospective data obtained by following Ara h2 specific antibodies during childhood proved variable. Some of the children followed had parallel changes across all the specific antibody classes tested. This was not a universal pattern and in other samples the specific IgE responses was either partly or completely unsynchronised with the other immunoglobulins tested.
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