title: Anaphylaxis and mortality induced by treatment of mice with anti-VLA-4 antibody and pertussis toxin.
abstract: Ab-mediated blockade of the adhesion molecule VLA-4 has been shown to ameliorate disease in human multiple sclerosis patients and experimental autoimmune encephalomyelitis (EAE) animal models. We wanted to determine whether anti-VLA-4 Ab treatment affected the function and persistence of autoreactive T cells in mice with EAE. Unexpectedly, we observed a high level of mortality in anti-VLA-4 mAb (PS/2)-treated mice with actively induced EAE despite decreased disease severity. Investigation of the underlying mechanism showed that injection of PS/2 mAb in combination with pertussis toxin resulted in anaphylaxis and mortality. Furthermore, the data showed that CD4(+) T cells were required for this effect and suggested a role for IL-1β and TNF-α in the underlying pathology. The results reveal a previously not appreciated deleterious effect of anti-VLA-4 Ab treatment in combination with exposure to pertussis toxin.
authors.affiliation: Department of Biology, University of Texas at San Antonio, San Antonio, TX 78249, USA.
authors.forename: Niannian
authors.initials: N
authors.lastname: Ji
authors.forename: Nagarjun
authors.initials: N
authors.lastname: Rao
authors.forename: Neal M
authors.initials: NM
authors.lastname: Guentzel
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Forsthuber
mesh_terms: D000707:Anaphylaxis / Q000235:genetics / Q000276:immunology* / Q000401:mortality*; D000818:Animals; D019138:Antibodies, Blocking / Q000008:administration & dosage; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D004338:Drug Combinations; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000401:mortality*; D005260:Female; D039041:Integrin alpha4beta1 / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016513:Mice, SCID; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000008:administration & dosage / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D037342:Pertussis Toxin / Q000008:administration & dosage*; D016019:Survival Analysis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D039041:Integrin alpha4beta1; C571326:MOG protein, human; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014409:Tumor Necrosis Factor-alpha; D037342:Pertussis Toxin