Differential induction of IgE-mediated anaphylaxis after soluble vs. cell-bound tolerogenic peptide therapy of autoimmune encephalomyelitis.
The ability of different forms of myelin peptides to induce tolerance for the treatment of preestablished murine experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, was evaluated. i.v. administration of myelin peptide-pulsed, ethylene carbodiimide-fixed syngeneic splenocytes, but not soluble myelin peptide monomers or oligomers, proved exceedingly effective at treating preestablished EAE, resulting in amelioration of disease progression. In addition to the lack of therapeutic efficacy of soluble peptide and peptide oligomer, administering them i.v. after the onset of clinical symptoms in many but not all peptide-induced EAE models led to a rapid-onset anaphylactic reaction characterized by respiratory distress, erythema, decreased body temperature, unresponsiveness, and, often, death. By using anti-IgE antibody treatments and mice with targeted mutations of the FcgammaRIII alpha-chain or the common gamma-chain of FcepsilonRI and FcgammaRI/III, we demonstrate that IgE crosslinking of FcepsilonRI appears to be necessary and sufficient for myelin peptide-induced anaphylaxis. The implications of these findings to myelin peptide/protein tolerance strategies for the treatment of multiple sclerosis are discussed.
Department of Microbiology-Immunology and Interdepartmental Immunobiology Center, The Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA.
Cassandra E
CE
Smith
Todd N
TN
Eagar
Jack L
JL
Strominger
Stephen D
SD
Miller
D000707:Anaphylaxis / Q000139:chemically induced*; D000818:Animals; D001831:Body Temperature; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006632:Histamine / Q000097:blood; D007073:Immunoglobulin E / Q000276:immunology / Q000378:metabolism*; D007136:Immunoglobulins / Q000097:blood; D051379:Mice; D018345:Mice, Knockout; D004676:Myelin Basic Protein / Q000008:administration & dosage / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000009:adverse effects* / Q000627:therapeutic use; D017455:Receptors, IgE / Q000378:metabolism
D007136:Immunoglobulins; D004676:Myelin Basic Protein; D010446:Peptide Fragments; D017455:Receptors, IgE; D007073:Immunoglobulin E; D006632:Histamine