27 novembre, 2006 23:20
Antibodies against myelin protein prominent in primary progressive MS
Last Updated: 2006-11-27 17:00:23 -0400 (Reuters Health)
NEW YORK (Reuters Health) - IgG antibodies to the myelin oligodendrocyte glycoprotein (MOG) appear to participate in the more severe type of multiple sclerosis (MS), investigators in Germany report in the PNAS Early Edition, published online on November 27.
Of the self-antigens previously evaluated in MS patients, none has a proven biological activity, senior author Dr. Bernhard Hemmer, from Heinrich Heine University in Dusseldorf, and his associates note.
MOG is present at the outermost surface of the myelin sheath, and anti-MOG antibodies have been implicated in the pathogenesis of MS, making it a "promising target" for further investigation of its role in MS. Up until now, researchers have evaluated fragments or linear constructs of MOG.
To construct a more natural model of MOG, Dr. Hemmer's team transduced human glial cells with full-length human MOG cDNA.
Serum of MS patients bound with high affinity to the extracellular domain of MOG in the transduced cells, but only to strictly conformational epitopes of the antigen. The authors note that anti-MOG antibody-positive sera killed transduced cells.
The researchers incubated rat brain sections with anti-MOG antibody-positive and antibody-negative serum. Only in those sections exposed to anti-MOG antibodies were myelin sheaths in the white matter strongly stained.
Finally, in a rat model of experimental autoimmune encephalomyelitis, injection of anti-MOG serum increased demyelination and axonal loss.
The IgG antibody titers to native MOG were significantly higher in all MS patient groups compared with control subjects. The highest prevalence was in patients with the primary progressive type of MS rather than the relapsing remitting form.
Dr. Hemmer and his associates conclude: "The occurrence of antibodies with demyelinating properties further supports the pathogenic role of the humoral immune system in MS and calls for the development of B cell directed therapies not only for relapsing remitting MS, but also for primary progressive MS.
PNAS Early Edition 2006.
