Abstract
Highly significant clinical, epidemiological and pathogenetic similarities between
multiple sclerosis (MS) and nasopharyngeal sinusitis has led to the hypothesis that
MS is caused by the inadvertent incorporation of the lymphatic drainage of the nasopharynx
into the extracellular fluid circulation of the CNS. It has been postulated that,
in response to antigenic and toxic products generated by the mucosal nasopharygeal
flora, the leptomeninges and CNS parenchyma acquire the characteristics of a persistently
stimulated lymphoid organ. Using an extensive panel of bacterial antibodies, tissues
from exceptionally early cases, identified and classified using multifactorial cluster
analysis, were screened for bacterial antigens using immunohistological methods. Anti-staphylococcal
antibodies detected antigen co-locating with IgG/C3d immune complexes in pre-demyelinating
and in primary lesions. The distribution of the antigen in relation to the morphogenesis
of early acute MS lesions is detailed. Evidence for the intrathecal processing of
staphylococcal antigen was obtained using isoelectric focusing and antigen imprinting
to identify antigen-specific oligoclonal bands. Employing a combination of isoelectric
focusing, western blotting and mass spectrometric analysis, evidence for the intrathecal
processing of staphylococcal β-haemolysin (sphingomyelinase) was obtained using CSF
from MS cases. While a myelinolytic transportable toxin may be an important component
in the pathogenesis of demyelination, in oligodendrocyte apoptosis, and in deviant
immune responses within the CNS, the detection of other as yet unidentified staphylococcal-positive
and negative oligoclonal bands points to the involvement of a cocktail of transportable
antigens leaking in a similar manner into the CNS from the paranasal sinus mucosal
tissues where these molecules are conserved by the resident flora to manipulate and
subvert the normal processes of local and systemic immunity. Evidence for the access
of other bacterial transportables to the CNS in MS should now be sought. The presence
of ‘high-output’ toxigenic bacterial strains within the nasopharyngeal flora of MS
patients should also be explored. The use of tracer molecules to detect and quantify
nose-to-brain transport in MS patients is clearly apposite.
Highlights
- Lymphatic drainage of the nasopharynx accesses the CNS in MS.
- Staphylococcal sphingomyelinase immune complex is detected in primary MS lesions.
- Evidence for nose-to-brain transport of other bacterial toxins should now be sought in MS.
Abbreviations:
CNS (Central nervous system), MS (Multiple sclerosis), ECF (Extracellular fluid compartment), MRI (Magnetic resonance imaging), OCB (Oligoclonal bands), EBV (Epstein–Barr Virus), HHV6 (Human Herpes Virus Type 6), SDS-PAGE (Sodium dodecyl sulphate-polyacrylamide gel electrophoresis), HRP (Horseradish peroxidase), HLA-DR (Human lymphocyte antigen-DR), DAB (3,3’-diaminobenzadine tetrahydrochloride), AEC (3-amino-9-ethyl carbazole), FITC (Fluorescein isothiocyanate), TRITC (Tetrarhodamine isothiocyanate), IEF (Isoelectric focusing), SSPE (Subacute sclerosing panencephalitis)Keywords
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Article info
Publication history
Published online: February 25, 2013
Accepted:
January 13,
2013
Received in revised form:
January 1,
2013
Received:
September 5,
2012
Identification
Copyright
© 2013 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
