Objective: To measure the prevalence of serum transcobalamin receptor antibodies (CD320ab) in a large cohort of patients with early Parkinson’s disease(PD) and to assess their relationship with serum and cerebrospinal fluid vitamin B12 and holotranscobalamin (holoTC) levels.

Background: About 25% of cobalamin (B12) in blood is bound to the transcobalamin protein and this complex is called holoTC.  The transcobalamin receptor (CD320) mediates the entry of holoTC into the central nervous system (CNS). CD320ab have recently been identified which block the uptake of holoTC to the CNS and are associated with “Autoimmune B12 Central Deficiency,” a condition in which individuals may develop neurological symptoms related to vitamin B12 deficiency despite normal serum vitamin B12, methylmalonic acid, and homocysteine levels. Since low vitamin B12 levels have been shown to be associated with PD, we sought to determine whether CD320ab are common in PD and, if so, whether they are associated with lower CSF B12/serum B12 and CSF holoTC/serum holoTC ratios.

Method: Measurements of baseline CSF and serum vitamin B12 and holoTC were available from participants with early untreated PD from the DATATOP study. Serum samples were tested using a Luminex assay to detect CD320ab. Samples were considered seropositive for the CD320 antigen (CD320ab+) using a fold change cutoff of 100. An unpublished study for this assay in a control population without PD showed a prevalence rate of approximately 6%.

Results: The prevalence rate of CD320ab+ was 12.7% (72/566). Mean age at diagnosis, Total Unified Parkinson’s Disease Rating Scale, and Mini-Mental Status Exam did not differ between CD320ab+ and CD320ab- participants. The mean (SD) CSF holoTC/serum holoTC ratio in men was lower in CD320ab+ than in CD320ab- (0.23 (0.07) vs 0.25 (0.02), p=0.03), but not in women.  The CSF B12/serum B12 ratios in CD320ab+ men and women did not differ from CD320ab- participants.

Conclusion: We found a higher prevalence of CD320ab+ in this cohort than in a control population. In CD320ab+ men, the finding of a lower CSF holoTC /serum holoTC ratio is consistent with prior observations that this antibody is associated with reduced entry of holoTC and B12 into the CNS. However, this was not observed in CD320ab+ women. Further studies are needed to determine whether CD320ab+ is associated PD progression and/or with an elevated risk for PD.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/prevalence-of-transcobalamin-receptor-antibodies-and-relationships-with-vitamin-b12-and-holotranscobalamin-in-parkinsons-disease/