Hyper-immunoglobulin D syndrome with mevalonate kinase deficiency

Where it participates (unsigned role)

1. Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels.

   Mevalonate → Trained immunity, an altered response to a later challenge after the first has ended source_derived_draftungraded
   Experimental context and source evidence

   evidence_span

   {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"}

   experimental_model

   Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate

   exposure

   Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients

   limitations

   The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response.

   nutrient_topic

   Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. · Beta-glucan

   organism

   Human

   plain_language

   It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained.

   primary_references

   [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025

   tissue_or_cell_type

   Monocyte

   Beta-glucan: a structural family rather than an agent, what decides whether a bound glucan actually signals, the complement route that a cereal and a yeast preparation share, and the unequal human evidence behind each (2026-09-22) · lines 463–474

   AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate · source_derived_draft · unverified_draft

   ### bg-mevalonate-not-cholesterol-trains Activation of the cholesterol synthesis pathway but not the synthesis of cholesterol itself is essential for training of myeloid cells, rather the metabolite mevalonate is the mediator of training via activation of IGF1-R and mTOR and subsequent histone modifications in inflammatory pathways, statins which block mevalonate generation prevent trained immunity induction, and monocytes of patients with hyper immunoglobulin D syndrome who are mevalonate kinase deficient and accumulate mevalonate have a constitutive trained immunity phenotype at both immunological and epigenetic levels. Condition category: normal nutrient_topic: Beta-glucan research collection; topical membership is not evidence of a direct clinical effect, and each preparation is recorded as its own entity with no family link joining any pair. plain_language: It is the intermediate and not the cholesterol that does the training, and people who cannot clear that intermediate are permanently trained. organism: Human tissue_or_cell_type: Monocyte experimental_model: Pharmacological and genetic dissection of the cholesterol synthesis pathway, with monocytes from patients accumulating mevalonate limitations: The patient arm is a natural experiment in the opposite direction, which is what makes the mevalonate assignment convincing. The statin result is inhibition of an induced laboratory response. exposure: Training of myeloid cells with statins to block mevalonate generation, and monocytes from mevalonate kinase deficient patients evidence_span: {"source_cache": "artifacts/glucan-research/29328908.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03", "start_char": 0, "end_char": 1173, "text_sha256": "c7d8052926f6be1dad87fedf0023f60ac5441b04f9b8e180c4b1e07edc83eb03"} [bg-p29328908] Metabolic Induction of Trained Immunity through the Mevalonate Pathway. (2018). https://pubmed.ncbi.nlm.nih.gov/29328908/ DOI: 10.1016/j.cell.2017.11.025

   Complete structured claim and evidence