Chemical- and Drug-Induced Allergic, Inflammatory, and Autoimmune Diseases Via Haptenation

Abstract

Haptens are small molecules that only elicit an immune response when bound to proteins. Haptens initially bind to self-proteins and activate innate immune responses by complex mechanisms via inflammatory cytokines and damage-associated molecular patterns and the subsequent upregulation of costimulatory signals such as cluster of differentiation 86 (CD86) on dendritic cells. Subsequent interactions between CD86 and CD28 on T cells are critically important for properly activating naive T cells and inducing interleukin 2 production, leading to the establishment of adaptive immunity via effector and memory T cells. Accumulating evidence revealed the involvement of haptens in the development of various autoimmune-like diseases such as allergic, inflammatory, and autoimmune diseases including allergic contact dermatitis, atopy, asthma, food allergy, inflammatory bowel diseases, hemolytic anemia, liver injury, leukoderma, and even antitumor immunity. Therefore, the development of in vitro testing alternatives to evaluate in advance whether a substance might lead to the development of these diseases is highly desirable. This review summarizes and discusses recent advances in chemical- and drug-induced allergic, inflammatory, and autoimmune diseases via haptenation and the possible molecular underlying mechanisms, as well as in vitro testing alternatives to evaluate in advance whether a substance might cause the development of these diseases.

SARS-CoV-2 Gut-Targeted Epitopes: Sequence Similarity and Cross-Reactivity Join Together for Molecular Mimicry

“…It is well established that genetic background is crucial for the development of Ads, but environmental factors are pivotal in their clinical expression [14][15][16][17]. In this sense, diet and hygiene [18], gut microbial antigenicity [19], multiple infectious agents [17,20,21], various vaccines [22,23], food processed additives [24][25][26], toxic agents [16], and even chemicals and drugs [27] have been suggested to take part in the environmentally induced autoimmunity of ASIA (autoimmune/inflammatory syndrome induced by adjuvants) [14,28]. Focusing on the gastrointestinal tract (GIT), many of the above-mentioned environmental factors dwell in the lumen and are associated with ADs [16][17][18][19][20][21]25,26,29].…”

MR1 deficiency enhances IL-17-mediated allergic contact dermatitis

“…The skin is repeatedly exposed to various antigenic substances of natural origin, cosmetics, metal accessories, and medical products of artificial origins, in the broad context of the environment ( 1 ), and the immunogenicity of these substances as sensitizers has been investigated ( 2 , 3 ). Antigen-presenting cells (APC) in skin exposed to sensitizers migrate to the draining lymph nodes (dLN) via lymphatic vessels and present them in the context of gene products of self-major histocompatibility complex (MHC) class Ia and II to antigen (Ag)-specific T cells ( 4 ).…”

Enthesitis and seronegative arthritis induced by Dupilumab: how relevant are these adverse events?

“…Autoimmune diseases constitute one of the groups of chronic illnesses with the highest burden of disease worldwide, impacting quality of life and organic functionality [1]. These diseases arise due to numerous risk factors, such as genetic and epigenetic factors, as well as environmental factors, which trigger a loss of immunological tolerance, leading to an immune response against an antigen from a tissue or organ system [1,2].…”

“…Autoimmunity and autoimmune conditions related to drug consumption are also frequently reported causes [2]. Moreover, they can pose a significant challenge in the medical approach to certain diseases, depending on the severity and mode of onset of autoimmunity, as well as the availability of a therapeutic arsenal for treating the underlying disease.…”

“…Moreover, they can pose a significant challenge in the medical approach to certain diseases, depending on the severity and mode of onset of autoimmunity, as well as the availability of a therapeutic arsenal for treating the underlying disease. For example, atopic dermatitis (AD) is a commonly encountered dermatopathy in dermatology [2,3]. Dupilumab, an IL-4/IL-13 receptor blocker, is a biological drug approved for use in moderate to severe AD [3].…”