Revisiting the effect of anti-VLA-4 monoclonal antibody treatment in experimental autoimmune encephalomyelitis (50.9)

Abstract

Abstract Blocking of adhesion molecule VLA-4 has been shown to ameliorate disease in human MS patients and in experimental autoimmune encephalomyelitis (EAE). We were interested in determining long-term effects of anti-VLA-4 monoclonal antibody (mAb) treatment on persistence and function of myelin-reactive T cells in EAE. Unexpectedly, we found that anti-VLA-4 mAb (PS/2) treated mice succumbed to toxic shock-like death after repeated injection of the mAb. Investigating the underlying mechanism we found that treatment of mice with PS/2 in combination with Pertussis toxin (PTX) which is commonly used to facilitate induction of disease in mouse EAE models resulted in death of the animals. Our results show that CD4+ T cells are critical for this effect and that systemic release of cytokines including IL-1 β and TNF-α may play a role. The results reveal a previously not appreciated effect of VLA-4 antibody treatment in mouse EAE model and could be relevant for the treatment of MS patients.