Earlier studies have shown that high doses of TNF-alpha increase apoptosis in human autoimmune T-cell clones. Based on these studies, a treatment approach was proposed to reduce or eliminate autoimmune T cells in patients with type 1 diabetes using drugs that temporarily elevate TNF levels. Here, we report the treatment of ankylosing spondylitis patient with a single high oral dose of Likopid (glucosaminyl-muramyl dipeptide), which aimed at increasing the levels of TNF-alpha in order to induce apoptosis of autoreactive T cells. The flow cytometric analysis of blood samples collected before and after treatment demonstrated massive elimination of CD8+ T cells. However, the treatment did not result in any notable therapeutic effect, and real-time PCR analysis demonstrated that stably expanded T-cell clones that were earlier tracked in this patient were unaffected. This report suggests that the controversial approach to eliminate autoimmune T-cell clones through overstimulation is not effective in treating ankylosing spondylitis.
Baetu TM, Kwon H, Sharma S, Grandvaux N, Hiscott J (2001) Disruption of NF-kappaB signaling reveals a novel role for NF-kappaB in the regulation of TNF-related apoptosis-inducing ligand expression. J Immunol 167:3164–3173PubMedGoogle Scholar
Ban L, Zhang J, Wang L, Kuhtreiber W, Burger D, Faustman DL (2008) Selective death of autoreactive T cells in human diabetes by TNF or TNF receptor 2 agonism. Proc Natl Acad Sci USA 105:13644–13649PubMedCrossRefGoogle Scholar
Faustman DL, Davis M (2009) The primacy of CD8 T lymphocytes in type 1 diabetes and implications for therapies. J Mol Med 87:1173–1178PubMedCrossRefGoogle Scholar
Coulombe F, Divangahi M, Veyrier F et al (2009) Increased NOD2-mediated recognition of N-glycolyl muramyl dipeptide. J Exp Med 206:1709–1716PubMedCrossRefGoogle Scholar
Farram E (1996) Profile of peptide technology Ltd Australasian Biotechnology 6:223–229Google Scholar
Mamedov IZ, Britanova OV, Chkalina AV et al (2009) Individual characterization of stably expanded T cell clones in ankylosing spondylitis patients. Autoimmunity 42:525–536PubMedCrossRefGoogle Scholar