Anaphylaxis to a self-peptide in the absence of mast cells or histamine.
Induction of T helper 1 (Th1) to Th2 deviation through administration of self- or altered self-peptides holds promise for treatment of autoimmunity. However, administration of self-peptides in models of autoimmunity can result in anaphylactic reactions. Although both IgE and IgG1 antibodies might be involved in the development of anaphylaxis to myelin peptides in experimental autoimmune encephalomyelitis in mice, the effector cells and molecules involved are not fully understood. Here we show that systemic anaphylaxis to the self-antigen myelin oligodendrocyte glycoprotein (MOG) 35-55 can occur in mice lacking mast cells (Kit(W)/Kit(W-v) mice) or histamine (histidine decarboxylase-deficient mice), but is prevented in mice lacking IL-4. Treatment of mice with CV6209, a platelet-activating factor antagonist, slightly reduced the incidence of anaphylaxis to self-MOG35-55 in this model, but more effectively protected mice against anaphylaxis to this peptide when self-MOG35-55 was administered in a different immunization protocol that omitted the use of Bordetella pertussis toxin as an adjuvant at the time of immunization. Thus, anaphylactic reactions to self-MOG can occur in the absence of mast cells or histamine, key elements of the classical IgE-, mast cell-, and histamine-dependent pathway of anaphylaxis.
Musio
Silvia
S
Immunology and Muscular Pathology Unit, Neurological Institute Foundation IRCCS Carlo Besta, Milan, Italy.
Pedotti
Paola
P
Mantegazza
Renato
R
Ohtsu
Hiroshi
H
Boon
Louis
L
Steinman
Lawrence
L
Galli
Stephen J
SJ
Pedotti
Rosetta
R
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000707:Anaphylaxis / Q000209:etiology / Q000276:immunology* / Q000517:prevention & control; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology / Q000494:pharmacology; D001886:Bordetella pertussis; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology / Q000628:therapy; D006023:Glycoproteins / Q000009:adverse effects / Q000276:immunology*; D006632:Histamine / Q000276:immunology*; D006640:Histidine Decarboxylase / Q000235:genetics; D007114:Immunization; D007073:Immunoglobulin E / Q000276:immunology; D015847:Interleukin-4 / Q000235:genetics / Q000276:immunology; D008407:Mast Cells / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000009:adverse effects / Q000276:immunology*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000502:physiology; D011726:Pyridinium Compounds / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000276:Adjuvants, Immunologic; D001427:Bacterial Toxins; D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C445081:myelin oligodendrocyte glycoprotein (35-55); C053321:CV 6209; D015847:Interleukin-4; D007073:Immunoglobulin E; D006632:Histamine; D006640:Histidine Decarboxylase