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	Niannian Ji, Nagarjun Rao, Neal M Guentzel, Bernard P Arulanandam, Thomas G Forsthuber
Journal	Journal of immunology (Baltimore, Md. : 1950) (J Immunol) Vol. 186 Issue 5 Pg. 2750-6 (Mar 01 2011) ISSN: 1550-6606 [Electronic] United States
PMID	21270409 (Publication Type: Comparative Study, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	Antibodies, Blocking Antibodies, Monoclonal Drug Combinations Integrin alpha4beta1 MOG protein, human Mog protein, mouse Myelin Proteins Myelin-Associated Glycoprotein Myelin-Oligodendrocyte Glycoprotein Tumor Necrosis Factor-alpha Pertussis Toxin
Topics	Anaphylaxis (genetics, immunology, mortality) Animals Antibodies, Blocking (administration & dosage) Antibodies, Monoclonal (administration & dosage) Drug Combinations Encephalomyelitis, Autoimmune, Experimental (genetics, immunology, mortality) Female Integrin alpha4beta1 (immunology) Mice Mice, Inbred C57BL Mice, Knockout Mice, SCID Myelin Proteins Myelin-Associated Glycoprotein (administration & dosage, immunology) Myelin-Oligodendrocyte Glycoprotein Pertussis Toxin (administration & dosage) Survival Analysis Tumor Necrosis Factor-alpha (biosynthesis, deficiency, genetics)

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