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Intrathecal IgG Synthesis: A Resistant and Valuable …
Natural IgM antibodies have a pentameric structure and are strong complement activators. In MS, IgM is the only immunoglobulin whose intrathecal synthesis correlates with intrathecal complement activation (), and the role of complement and antibodies in demyelination and axonal damage, the cause of permanent disability in this disease, has been clearly demonstrated (). Moreover, in an experimental model, anti–myelin lipid IgM, but not IgG, antibodies induce CNS demyelination and prevent remyelination (). These data suggest that the presence of IgM anti–myelin lipids in CSF can be important in the physiopathology of MS. To investigate this, we studied the relationship of these antibodies with disease course in a group of patients in whom the presence of OCMBs was studied at disease onset. In this group were 15 patients with LS-OCMBs, 7 patients with OCMBs that did not recognize myelin lipids, and 26 patients lacking IgM bands. First we evaluated the probability of remaining free of relapses. We found that patients with LS-OCMBs developed a second relapse earlier than those without LS-OCMBs. Differences were more significant than those obtained when comparing patients with and without OCMBs, regardless of lipid specificity, and indicate a strong correlation between the presence of anti–lipid IgM antibodies and an aggressive disease course in MS. These data were confirmed by evaluating the number of relapses and the disability. Patients with LS-OCMBs suffered more relapses during follow-up and had higher disability scores at the end of the study than those without LS-OCMBs.
It has been postulated that MS is an autoimmune disease, and considerable efforts have been made to find a particular antigen associated with its physiopathology (–). The presence of T cells, macrophages, and antibodies in MS demyelinating plaques has been established (). It has been postulated that T cells and macrophages play an important role in the inflammatory response observed in MS and that antibodies and complement participate in initial plaque development (, ). Increasing evidence indicates that IgM antibodies are also involved in this process. In this disease, local CNS (intrathecal) synthesis of IgM, but not of IgG or IgA, correlates with intrathecal synthesis of complement component C3 () and with the cerebrospinal fluid (CSF) concentration of myelin basic protein, an index of demyelination ().
Intrathecal IgG synthesis in multiple sclerosis ..
Intrathecal synthesis of immunoglobulin gamma (IgG) synthesis is frequently observed in patients with multiple sclerosis (MS). Whereas the extent of intrathecal IgG synthesis varies largely between patients, it remains rather constant in the individual patient over time. The aim of this study was to identify common genetic variants associated with the IgG index as a marker of intrathecal IgG synthesis in MS.
The extent of intrathecal IgG in MS is influenced by the IGHC locus. No association with susceptibility to MS was found. Therefore GM haplotypes might affect intrathecal IgG synthesis independently of the underlying disease.
Oligoclonal bands are detected in CSF in multiple sclerosis
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