Wednesday, September 13, 2006

Research: Another angle on neutralizing antibodies

So we all know that lots of us who take interferon-beta have developed antibodies to the stuff, which might be reducing the effectiveness of the stuff. If I understand this abstract correctly, the antibodies might also be messing with the interferon-beta your body is producing on its own. Is that a problem?
Arch Neurol. 2006 Sep;63(9):1296-9.
Potential for interferon Beta-induced serum antibodies in multiple sclerosis to inhibit endogenous interferon-regulated chemokine/cytokine responses within the central nervous system.
Shapiro AM, Jack CS, Lapierre Y, Arbour N, Bar-Or A, Antel JP.

BACKGROUND: A proportion of patients with multiple sclerosis (MS) receiving systemic interferon beta therapy will develop serum neutralizing antibodies (NAbs) that can reduce the activity of the drug. Interferon-beta (IFN-beta) is produced by glial cells within the central nervous system. Although systemic interferon beta does not access the central nervous system, titers of serum NAbs may be sufficient that some will access the central nervous system. OBJECTIVE: To address whether serum samples that contain high titers of NAbs could inhibit glial cell production of chemokines and cytokines that are regulated by endogenous IFN-beta. DESIGN: We used an in vitro assay involving toll-like receptor 3 ligand (polyinosinic-polycytidylic acid) signaling to assess the effect of serum samples containing high titers of NAbs (1800-20 000 U) on production of the chemokine CXCL10 and the cytokine interleukin 6 by human astrocytes. RESULTS: Serum samples positive for NAbs significantly inhibited polyinosinic-polycytidylic acid-induced CXCL10 and IL-6 production by astrocytes. CONCLUSION: High-titer NAbs to interferon beta may block endogenous IFN-beta function and alter the chemokine/cytokine microenvironment within the central nervous system, thereby modulating the profile and course of the local inflammatory response.


1 comment:

Beth said...

The paper didn't test if the IFNbeta abs DID interfere- they haven't shown that they get to the central nervous system although titres are high in periphery- they tested if they were high could they cause problems. I gather that the main function of therapeutic IFNbeta is to reduce the amount of IFNgamma and cause a shift from Th1 to Th2 (or the other way around I always get it mixed up)- so it is working in the periphery and the end result is less T cells that get into the CNS.