More MS news articles for April 2002

Toll-Like Receptors Linked to Autoantibody Formation

http://www.medscape.com/viewarticle/431650

NEW YORK (Reuters Health) Apr 11 - The mechanism behind autoimmunity involved in rheumatoid arthritis and systemic lupus erythematosus appears to involve a Toll-like receptor, a US team of investigators report in April 11th issue of Nature. This finding may lead to new therapies for autoimmune diseases that would not require targeting T cells.

Dr. Ann Marshak-Rothstein, of the Boston University School of Medicine, and associates developed a model based on a transgenic mouse strain susceptible to autoimmune disorders that harbor high concentrations of rheumatoid-factor (RF) autoantibodies in their bloodstream. They found that the B cells in these mice are activated by immune complexes of immunoglobulin gamma-2a (IgG2a) and nucleosomes.

Further research showed that these immune complexes synergistically engage both the B-cell receptor and Toll-like receptor 9 (TLR9). Complement receptors are not required. B cells positive for rheumatoid factor then become autoreactive, independent of any T cell involvement.

TKR receptors usually sense pathogens by detecting exogenous microbial ligands. "The ability of microbial pathogen associated molecular patterns to engage TLR and/or upregulate TLR expression and thus create a synergy with autoantibody-autoantigen immune complexes might explain the association between infection and disease flares," the investigators write.

In an editorial, Drs. Carola G. Vinuesa and Christopher C. Goodnow of The Australian National University in Canberra, add that rheumatoid-factor autoantibodies are also produced during immune responses to infection, presumably through foreign DNA complexes with IgG. The same mode of co-engaging B cell receptors and TLR receptors may again result in autoantibody formation.

"Drugs that specifically target toll-like receptor signaling pathways could be promising new treatments for antibody-mediated autoimmune diseases or their complications," they suggest.

Nature 2002;416:595-598,603-607.
 

© 2002 Reuters Ltd