We thank Dr. Brenner for a testable hypothesis on how CCSVI- related breakdown of the blood brain barrier may result in development of autoimmunity against proteins of the central nervous system (CNS) and thus cause multiple sclerosis (MS).
Does CCSVI cause the development of
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We thank Dr. Brenner for a testable hypothesis on how CCSVI- related breakdown of the blood brain barrier may result in development of autoimmunity against proteins of the central nervous system (CNS) and thus cause multiple sclerosis (MS).
Does CCSVI cause the development of autoantibodies against CNS proteins in humans? Khan et al. made the observation that development of MS was not reported as a complication after removal of jugular veins in head and neck cancer. [6] Considering the articles cited by Dr. Brenner [2,3], it is possible that there was no CNS damage in these patients and perhaps long-term survival is required to allow for the development of MS.
In our study, oligoclonal bands were present in 98% of the MS patients. [7] We did not search for CNS antigens because oligoclonal bands in MS are of low affinity [8] and difficult to analyze. There is evidence that development of autoimmunity to CNS proteins can be neuroprotective. [9] The sceptical reader may still have a valid point in asking if MS is an autoimmune disease.
Sena et al. address monitoring treatment response in MS. Our data are similar to that of Dr. Sena's group and shows the potential for estimating biological activity of interferons indirectly by measuring biomarkers for activated glia. [4,7,10]
In the accompanying editorial to our study, Drs. van Rensburg and van Toorn [11] outlined a more holistic approach to longitudinally investigating the iron metabolism in patients with MS. In this context, knowledge of the patient's treatment as pointed out by Dr Sena is essential.
In our cohort, only nine patients were on interferon (Avonex n=3, Betaferon n=4, Rebif 22 n=2). The post-hoc analysis showed no significant differences in CSF ferritin levels between those treated with interferon and naive patients either at baseline (p=0.18) or 3-year follow-up (p=0.41), but the study was underpowered for a meaningful analysis.
A future study investigating the effect of interferon therapy in MS may also need to consider the development of drug-related autoantibodies.
References
6. Khan O, Filippi M, Freedman MS et al. Chronic cerebrospinal venous insufficiency and multiple sclerosis. Ann Neurol 2010;67: 286-290.
7. Petzold, A, Eikelenboom M, Gveric D et al. Markers for different glial cell responses in multiple sclerosis: Clinical and pathological correlations. Brain, 2002;125: 1462-1473.
8. Luxton RW, Zeman A, Holzel H et al. Affinity of antigen-specific IgG distinguishes multiple sclerosis from encephalitis. J Neurol Sci 1995;132:11-19.
9. Yoles E, Hauben E, Palgi O et al. Protective autoimmunity is a physiological response to CNS trauma. J Neurosci , 2001;21:3740-3708.
10. Petzold A, Brassat D, Mas P et al. Treatment response in relation to inflammatory and axonal surrogate marker in multiple sclerosis. Mult Scler 2004;10:281-283.
11. van Rensburg SJ. Van Toorn R. The controversy of CCSVI and iron in multiple sclerosis: Is ferritin the key? Neurology 2010;75:1581-1582.
Disclosures: See original article for full disclosure list.
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