Pre-print: Transcobalamin Receptor Autoantibodies in Central Vitamin B12 Deficiency

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https://www.medrxiv.org/content/10.1101/2023.08.21.23294253v1.full-text

Abstract​

Vitamin B12 is critical for hematopoiesis and myelination.1 Deficiency can cause neurologic deficits including loss of coordination, spasticity, and cognitive decline.2,3,4 However, diagnosis relies on vitamin B12 measurement in the blood which may not accurately reflect levels in the brain. Here, we discovered an autoimmune cause of vitamin B12 deficiency restricted to the central nervous system (CNS), termed autoimmune B12 central deficiency (ABCD). Using programmable phage display, we identified an autoantibody targeting the transcobalamin receptor (CD320) in a patient with progressive tremor, ataxia, and scanning speech. Patient immunoglobulins impaired cellular uptake of vitamin B12 in vitro. Despite normal serum levels, vitamin B12 was nearly undetectable in her cerebrospinal fluid (CSF). Immunosuppressive treatment and high-dose systemic vitamin B12 supplementation were associated with increased CSF B12 levels and clinical improvement. Autoantibodies targeting the same epitope of CD320 were identified in 7 other patients with neurologic deficits of unknown etiology and in 6 percent of healthy controls. In 132 paired serum and CSF samples, detection of anti-CD320 in the blood predicted B12 deficiency in the brain. These findings elucidate a new autoimmune cause of metabolic neurologic disease that may be amenable to immunomodulatory treatment and/or nutritional supplementation.

 

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So, does this mean people requiring cupious amounts of B12 are battling a receptor issue? Kind of what happens with vitamin D receptor issues requiring high dose vitamin D approaches like the Coimbra Protocol

 

[datadragon]

So, does this mean people requiring cupious amounts of B12 are battling a receptor issue? Kind of what happens with vitamin D receptor issues requiring high dose vitamin D approaches like the Coimbra Protocol

That study is interesting. I think related to ME/CFS, B12 function is inactivated and depleted as I mentioned here more likely for completely different reasons than that https://forums.phoenixrising.me/thr...-van-konynenburg-documents.90623/post-2441698 However this research I posted here does mention that short chain fatty acids including butyrate exert modulatory effects on intrinsic B cell functions even at moderate concentrations, thereby is what shapes normal and effective antibody and autoantibody responses. So that means that when butyrate is low it can cause the dysregulated antibody responses leading to generation of autoantibodies And with that study you posted it suggests to start checking for that in different conditions related to inflammation as yet another reason for subsequent B12 problems. It was found in around 6% in your study. https://forums.phoenixrising.me/threads/bc007-what-are-your-thoughts.87520/post-2441668

 

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If that's true, would butyrate supplements be expected to help? Would that be a viable way to test the hypothesis?

 

[datadragon]

If that's true, would butyrate supplements be expected to help? Would that be a viable way to test the hypothesis?

It is not a hypothesis since it was showing the mechanism of how it works- According to that research, natural Short Chain Fatty Acid histone deacetylase (HDAC) inhibitors butyrate and propionate play an important role in preventing or dampening dysregulated antibody responses, which can lead to generation of autoantibodies or allergic IgE. HDAC inhibitors valproic acid, butyrate, and propionate epigenetic modifiers exert modulatory effects on intrinsic B cell functions even at moderate concentrations, thereby shaping effective antibody and autoantibody responses. Other research is showing low butyrate in ME/CFS. Butyrate appears it can help in conditions where there is dysregulated antibody responses/autoantibodies in general as a HDAC inhibitor. Only around 6% were found with autoantibodies to transcobalamin receptor CD320 so that suggested to start checking for that in different conditions related to inflammation.