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Biotech / Medical : Neurocrine Biosciences (NBIX) -- Ignore unavailable to you. Want to Upgrade?


To: mopgcw who wrote (986)9/18/2002 11:13:45 AM
From: scaram(o)uche  Read Replies (1) | Respond to of 1834
 
Clin Immunol 2002 Aug;104(2):105

Persistence of immune responses to altered and native myelin antigens in patients with multiple sclerosis treated with altered Peptide ligand.

Kim H, Antel J, Duquette P, Alleva D, Conlon P, Bar-Or A.

Neuroimmunology Unit, Department of Neurology, Montreal Neurological Institute, McGill University, Montreal, Canada

Altered peptide ligands (APLs) can modulate responses of T cells to native peptide antigens implicated in the pathogenesis of autoimmune diseases. An APL of the putative target antigen myelin basic protein (MBP) peptide 83-99 has been used in abbreviated clinical trials in patients with multiple sclerosis (MS). Our objective was to assess the long-term persistence, and characteristics, of the APL-induced immune response in such patients. We measured the ex vivo proliferative frequency to the APL and native MBP, the cross-reactivity, and the cytokine production by these lines. We found that a 4- to 16-week course of APL therapy could induce a persistent (2-4.5 year) increase in the frequency of T cells responsive to both the APL and the native MBP in a select number of patients. These T cells produced high levels of IL-5, contrasting with the pretreatment observation that the responses to either antigen were IFNgamma (Th1) dominant. Our results indicate that APL therapy can induce persistent Th2-directed immune deviation. Understanding the impact of such APL-induced immune responses on MS disease activity will require additional clinical trials that incorporate careful monitoring of both clinical and immunological parameters.