An unexpected version of horror autotoxicus: anaphylactic shock to a self-peptide

Abstract

EAE can refer either to experimental autoimmune encephalomyelitis or experimental allergic encephalomyelitis. Although EAE is classically a prototypic T helper 1 (TH1) cell-mediated autoimmune disease, it can also be induced by TH2 cells. Characteristically, the most severe manifestation of allergy, anaphylaxis, is associated with exposure to a foreign antigen that is often derived from medication, insect venom or food. We report here that, after self-tolerance to myelin is destroyed, anaphylaxis may be triggered by a self-antigen, in this case a myelin peptide. "Horror autotoxicus", which was initially described by Ehrlich, may not only include autoimmunity to self, it may also encompass immediate hypersensitivity to self, which leads to shock and rapid death.

Peripheral Tolerance Induction Using Ethylenecarbodiimide-Fixed APCs Uses both Direct and Indirect Mechanisms of Antigen Presentation for Prevention of Experimental Autoimmune Encephalomyelitis

“…Unlike soluble i.v. tolerance induction in which the tolerizing Ag can induce an anaphylactic response resulting in death of treated mice (40), Ag-SP tolerance did not induce an allergic response regardless of the Ag used or the time of treatment (39) demonstrating its effectiveness at both preventing and treating ongoing disease (40,41). The potential dangers in of therapies using soluble peptides were illustrated in a recent clinical trial using an myelin basic protein 85-99 altered peptide that were terminated due to systemic hypersensitivity reactions (42).…”

Low-Dose Peptide Tolerance Therapy of Lupus Generates Plasmacytoid Dendritic Cells That Cause Expansion of Autoantigen-Specific Regulatory T Cells and Contraction of Inflammatory Th17 Cells

“…In lupus patients, the most damaging side effects and morbidity occur from chronic life-long maintenance therapy with steroids and cytotoxic agents and, despite their use, flares and progression of renal disease occurs. Our therapy with H4 71-94 peptide has certain advantages: 1) it is an unaltered peptide ligand, being naturally occurring with evolutionarily conserved sequences, ubiquitous, expressed in the thymus during ontogeny (49), and not causing Th2 deviation (unlike altered peptide ligands) (50), and therefore, not associated with anaphylactic/allergic reactions; 2) it is effective at low doses and by s.c. administration in an animal model of lupus; 3) it generates long-lasting, Ag-specific regulatory T cells that suppress pathogenic autoantibody production and lupus nephritis; 4) it is cross-reactive, inducing "tolerance spreading" to other pathogenic T cell autoepitopes of lupus, but not to exogenous Ags; and 5) it is recognized by autoimmune T cells of all lupus patients tested irrespective of their HLA type.…”

Cell-based gene therapy experiments in murine experimental autoimmune encephalomyelitis

“…30 In addition, our protocol was designed to deliver a low-level, constant exposure to antigen, and this may be the reason we have never observed the anaphylactic response seen in some cases upon repeated injection of antigen. 53 In our previous study, we used the SJL/J model of EAE in which the PLP 139-151 epitope is immunodominant. This appears to be due to the high frequency of PLP 139-151-reactive T cells observed in these mice.…”