Immune regulation of multiple sclerosis by transdermally applied myelin peptides
Article first published online: 28 OCT 2010
Copyright © 2010 American Neurological Association
Annals of Neurology
Volume 68, Issue 5, pages 593–601, November 2010
How to Cite
Juryńczyk, M., Walczak, A., Jurewicz, A., Jesionek-Kupnicka, D., Szczepanik, M. and Selmaj, K. (2010), Immune regulation of multiple sclerosis by transdermally applied myelin peptides. Ann Neurol., 68: 593–601. doi: 10.1002/ana.22219
- Issue published online: 28 OCT 2010
- Article first published online: 28 OCT 2010
- Manuscript Accepted: 6 AUG 2010
- Manuscript Revised: 30 JUL 2010
- Manuscript Received: 21 JUN 2010
- Polish Ministry of Science. Grant Number: N402 4355 33
Antigen-specific therapy targeting selective inhibition of autoreactive responses holds promise for controlling multiple sclerosis (MS) without disturbing homeostasis of the whole immune system. Key autoantigens in MS include myelin proteins, such as myelin basic protein (MBP), proteolipid protein (PLP), and myelin oligodendrocyte glycoprotein (MOG). In this study, we examined the effect of transdermal therapy with myelin peptides on immune responses in the skin, lymph nodes, and peripheral blood immune cells of MS patients.
In a 1-year placebo-controlled study, 30 patients with relapsing-remitting MS were treated transdermally with a mixture of 3 myelin peptides: MBP85-99, PLP139-151, and MOG35-55, or placebo. The phenotype of immune cells in the skin was assessed using immunohistochemistry. Cell populations in lymph nodes were analyzed using flow cytometry. In peripheral blood immune cells, cytokine production was measured by enzyme-linked immunosorbent assay, and myelin-specific proliferation was examined by carboxyfluorescein succinimidyl ester-based assay.
We found that myelin peptides applied transdermally to MS patients activated dendritic Langerhans cells in the skin at the site of immunization and induced a unique population of granular dendritic cells in local lymph nodes. In the periphery, transdermal immunization with myelin peptides resulted in the generation of type 1, interleukin-10–producing regulatory T cells, suppression of specific autoreactive proliferative responses, and suppression of interferon-γ and transforming growth factor-β production.
We demonstrate for the first time the immunoregulatory potential of transdermal immunization with myelin peptides in MS patients. Ann Neurol 2010;68:593–601