Allergic and autoimmune reactions to xenobiotics: how do they arise?

Abstract

Induction of allergic and autoimmune reactions by drugs and other chemicals constitutes a major public health problem. Elucidation of the underlying mechanisms might help improve diagnostic tools and therapeutic approaches. Here, Peter Griem and colleagues focus on several aspects of neoantigen formation by xenobiotics: metabolism of xenobiotics into reactive, haptenic metabolites; polymorphisms of metabolizing enzymes; induction of costimulatory signals; and sensitization of T cells.

A review of PAH exposure from the combustion of biomass fuel and their less surveyed effect on the blood parameters

“…PAHs modulate the signal transduction (Tannheimer et al 1997) and can induce oxidative stress (Burczynski et al 1999;Kamal et al 2015). The PAHs can downregulate the lymphocytes, neutrophils and macrophages (WHO 2010a(WHO , 2010b, whereas their metabolites are suspected to cause autoimmunity and hypersensitivity through the formation of adducts with proteins, or via inducing cellular apoptosis (Griem et al 1998). Increases in MCVand red cell distribution width are characteristics of hemolytic anemia (Bain 1996;Kamal et al 2014b).…”

DNFB activates MAPKs and upregulates CD40 in skin-derived dendritic cells

“…Allergic contact dermatitis (ACD), one of the most common inflammatory skin disorders [1,2], is a delayed-type hypersensitivity reaction caused by a wide range of low molecular weight reactive chemicals (haptens). These haptens enter the skin and bind self-proteins, converting them into immunogenic peptides that are captured and processed by dendritic cells (DCs) [1,[3][4][5].…”

Drug Metabolism and Reactive Metabolites

“…This suggests that the small molecules such as drugs can be immunogenic (i.e., capable of eliciting an immune response) through a reactive metabolite covalently binding to a protein to form a hapten which is then seen as foreign by the immune system [30]. The types of hypersensitivities that are best understood by this mechanism are those responses mediated by IgE antibodies directed against a drug-hapten conjugated to protein, such as those observed for penicillin.…”