Cerebrospinal fluid and plasma distribution of anti-α-synuclein IgMs and IgGs in multiple system atrophy and Parkinson's disease.

Abstract Introduction Naturally occurring autoantibodies (nAbs) against α-synuclein (α-syn) are ubiquitous and may play important roles in the pathogenesis of Multiple System Atrophy (MSA) and Parkinson`s disease (PD). Recently, we reported reduced high-affinity/avidity anti-α-syn nAbs in plasma from MSA and PD patients along with different diverse inter-group immunoglobulin (Ig)G subclass distributions. To what extent these observations may be reflected in the cerebrospinal fluid (CSF) is unknown. Methods Using competitive and indirect ELISAs, we investigated in a cross-sectional cohort of MSA and PD patients the affinity/avidity of CSF anti-α-syn nAbs and as well as CSF and plasma distribution of IgG and IgM nAbs subclasses in a cross-sectional cohort of MSA and PD patients. Results Repertoires of high-affinity/avidity anti-α-syn IgG nAbs in CSF samples from MSA and PD patients were reduced compared to controls. In regard to IgM subclasses Further, anti-α-syn IgM nAb levels were reduced in both CSF and plasma in of from MSA patients while reduced only in plasma in of from PD patients. Interestingly, anti-α-syn IgG subclasses presented disease-specific profiles of anti-α-syn IgG reactive subclasses in both CSF and plasma. Whereas MSA patients have increased anti Anti-α-syn IgG1, IgG2 and IgG3 levels were increased in MSA patients, whereas PD patients have showed increased anti-α-syn IgG2 and reduced anti-α-syn IgG4 levels. Conclusions Differences in the distribution of anti-α-syn nAbs seem to be a common feature in synucleinopathies. Our data add further support to the idea that MSA and PD patients may have a compromised immune reactivity towards α-syn. PD and MSA α-syn-specific systemic immunological responses may reflect their different disease pathophysiology and encourages to further investigate these immunological mechanisms.