# Pathogenic and Nonpathogenic Antibody Responses in Allergic Diseases

## TL;DR

This review explores how some people have allergy-related antibodies without symptoms, and what factors determine whether these antibodies cause allergic disease or not.

## Contribution

The paper introduces a two-stage model to explain transitions between nonpathogenic and pathogenic antibody responses in allergic diseases.

## Key findings

- Allergen-specific IgE can exist without causing allergy symptoms in some individuals.
- Environmental and inflammatory factors influence the development of pathogenic versus nonpathogenic antibody responses.
- Differences in antibody characteristics like glycosylation and IgE/IgG ratios affect disease severity and treatment response.

## Abstract

Allergen‐specific antibodies, particularly of the IgE class, are a hallmark of many allergic diseases. Yet paradoxically, (1) a proportion of healthy individuals possess allergen‐specific IgE without clinical signs of allergy; (2) some, but not all, allergic individuals develop a more severe disease over time or fail to respond to allergen‐specific immunotherapy; and (3) allergen‐specific IgG antibodies can inhibit IgE‐mediated responses but they can also induce allergic reactions. In this review, we discuss the occurrence of and transition between nonpathogenic and pathogenic allergen‐specific antibody responses in the light of a two‐stage model. We recapitulate different factors and scenarios that may induce different inflammatory conditions and qualitatively distinct allergen‐specific T‐ and B‐cell responses, influencing IgE origins and affinities, IgE/IgG(4) ratios, IgG effector functions, antibody glycosylation patterns, Fc and glycan‐binding receptor expression and involvement, and ultimately their propensity to elicit allergic responses. Differences in these antibody characteristics may determine the onset of symptomatic allergy and the severity or remission of the disease.

Allergen‐specific antibodies can be detected in a large proportion of individuals. Still, only a fraction suffer from clinical signs of allergic disease, and of these, some, but not all, will develop more severe forms of the disease over time or respond to allergen‐specific immunotherapy. Here, we review the concept of nonpathogenic versus pathogenic antibody responses in allergy and discuss the impact of environmental factors and inflammatory conditions on shaping antibody responses in allergic individuals.