Single high-dose treatment with glucosaminyl-muramyl dipeptide is ineffective in treating ankylosing spondylitis.
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.
Shemiakin-Ovchinnikov Institute of Bioorganic Chemistry, Moscow, Russia.
Olga V
OV
Britanova
Dmitriy B
DB
Staroverov
Anna V
AV
Chkalina
Alexei A
AA
Kotlobay
Ekaterina S
ES
Zvezdova
Anna G
AG
Bochkova
Dmitriy M
DM
Chudakov
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000068879:Adalimumab; D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D013167:Spondylitis, Ankylosing / Q000188:drug therapy*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000473:pathology; D017211:Treatment Failure
D000276:Adjuvants, Immunologic; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D000119:Acetylmuramyl-Alanyl-Isoglutamine; C063429:glucosaminylmuramyl-2-alanine-D-isoglutamine; D000068879:Adalimumab