Objective: To measure serum & CSF transcobalamin receptor antibodies (CD320ab) in patients with early Parkinson’s disease (PD) and to assess their relationships to CSF vitamin B12 (B12), holotranscobalamin (holoTC), baseline features and progression.

Background: The transcobalamin receptor (CD320) enables the entry of the B12 transporter, holoTC, into the central nervous system (CNS). CD320ab have recently been identified which block CNS uptake of holoTC and are associated with “Autoimmune B12 Central Deficiency,” in which neurological symptoms related to B12 deficiency occur despite normal serum B12. Since low B12 levels are associated with severity and rate of progression of PD, we sought to determine whether CD320ab occur in PD, and whether they are associated with baseline features or clinical progression.

Method: Measurements of baseline CSF & serum B12 and holoTC were available from participants with early PD from the DATATOP study. Serum and CSF samples were tested using a Luminex assay to detect CD320ab. Serum samples were considered seropositive for the CD320 antigen (CD320ab+) using a fold change cutoff of 100 and CSF samples at a 10-fold cutoff. An unpublished study for this assay in a control population without PD showed a seroprevalence rate of approximately 9.4%.

Results: The CD320ab+ prevalence rate was 12.7% (72/566) in serum and 12.5% (68/546) in CSF. At the defined cutoffs, there was a strong correlation between the samples (phi=0.9, p<0.001).  Moreover, continuous serum and CSF titers were moderately correlated (r=0.6, p<0.001). The mean (SD) CSF holoTC/serum holoTC ratio in men was lower in serum CD320ab+ than in CD320ab- (0.23 (0.07) vs 0.25 (0.02), p=0.03), but not in women.  A similar trend for CSF in men was not significant (p=0.09).  Baseline characteristics, including total UPDRS and MMSE, and annualized changes in these scores did not differ between serum or CSF CD320ab+ and CD320ab- participants.

Conclusion: Serum & CSF CD320ab+ correlated well and had a prevalence of about 12.5%.  The lower CSF holoTC /serum holoTC ratio in serum CD320ab+ men (and a similar non-significant trend in CSF CD320ab+ men) is consistent with prior observations that this antibody is associated with reduced entry of holoTC and B12 into the CNS. Further studies are needed to determine whether CD320ab+ are more common in PD than in normal aging.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/relationships-of-serum-csf-transcobalamin-receptor-antibodies-to-csf-vitamin-b12-holotranscobalamin-and-clinical-progression-in-parkinsons-disease/