{"id":"b878b524-334c-54a4-9758-66b341e69be9","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-antibody-level-gates-the-response","predicate":"enables","statement":"At the end of infusion free serum antibody levels decreased, circulating immune complex levels increased and complement activation was observed, at approximately 1 to 4 hours after end of infusion increased expression of cytokines and chemokines, a 1.5 to 4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed, low-antibody subjects with levels below 20 micrograms per millilitre typically showed minimal changes except when their levels rose above 20 micrograms per millilitre after repeated dosing, mild-to-moderate infusion-related reactions occurred in subjects with antibody at or above 20 micrograms per millilitre, and premedications alleviated some of the infusion-related reactions but also inhibited cytokine responses.","claim_class":"observational","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"dabdd321-fa98-5928-9607-c1c73775fc53","mechanism_event_label":"Below a certain antibody level almost nothing happened; above it, the drug worked and also caused the infusion reactions.","subject":{"id":"afe6f619-e984-533b-b63a-83b4e77aab4f","slug":"anti-beta-glucan-antibodies","display_name":"Naturally occurring anti-beta-glucan IgG antibodies","entity_type_key":"protein"},"object":{"id":"a04b52d4-0af9-594a-bbda-51a16406d235","slug":"imprime-pgg","display_name":"Imprime PGG / BTH1677, a soluble yeast beta-(1->3)/(1->6)-glucan","entity_type_key":"drug"},"evidence_count":1,"mechanism_event":{"id":"dabdd321-fa98-5928-9607-c1c73775fc53","stable_key":"10629adf-a816-5b7b-82db-a76bfbb946f2:bg-antibody-level-gates-the-response-event","event_type":"observed_intervention","label":"Below a certain antibody level almost nothing happened; above it, the drug worked and also caused the infusion reactions.","description":"At the end of infusion free serum antibody levels decreased, circulating immune complex levels increased and complement activation was observed, at approximately 1 to 4 hours after end of infusion increased expression of cytokines and chemokines, a 1.5 to 4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed, low-antibody subjects with levels below 20 micrograms per millilitre typically showed minimal changes except when their levels rose above 20 micrograms per millilitre after repeated dosing, mild-to-moderate infusion-related reactions occurred in subjects with antibody at or above 20 micrograms per millilitre, and premedications alleviated some of the infusion-related reactions but also inhibited cytokine responses.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"5146ad84-5cac-5c1c-848c-302bb17fa252","slug":"immune-complex-formation","display_name":"Formation of a glucan and antibody immune complex","entity_type_key":"cellular_process"},"role":"measured_step","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b3dedb88-ea6f-5178-ac07-17b1aa869d96","slug":"neutrophil","display_name":"Polymorphonuclear neutrophil","entity_type_key":"cell_type"},"role":"mobilised_cell","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"dca88fca-981a-5a11-8a73-997d334bf9d4","slug":"monocyte","display_name":"Monocyte","entity_type_key":"cell_type"},"role":"mobilised_cell","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"d5c401db-29fb-5719-a1de-9d859e2317dc","slug":"infusion-related-reaction","display_name":"Infusion-related reaction","entity_type_key":"cellular_process"},"role":"linked_harm","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"e95326ee-2dc4-52cb-9140-4f5b2f8121a6","slug":"classical-complement-pathway","display_name":"The classical complement pathway","entity_type_key":"cellular_process"},"role":"activated_pathway","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"afe6f619-e984-533b-b63a-83b4e77aab4f","slug":"anti-beta-glucan-antibodies","display_name":"Naturally occurring anti-beta-glucan IgG antibodies","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"a04b52d4-0af9-594a-bbda-51a16406d235","slug":"imprime-pgg","display_name":"Imprime PGG / BTH1677, a soluble yeast beta-(1->3)/(1->6)-glucan","entity_type_key":"drug"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/glucan-research/30988115.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d\", \"start_char\": 0, \"end_char\": 1787, \"text_sha256\": \"bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Single and multiple intravenous infusions in healthy volunteers stratified by pre-treatment antibody level, with and without premedication","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Imprime PGG 4 milligrams per kilogram intravenously, with antihistamine and corticosteroid premedication in some subjects","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Healthy volunteers and pharmacodynamic endpoints only. Nothing here measures a tumour outcome, so the antibody strata are not validated treatment-selection thresholds.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"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.","comparator":null,"unit":null,"notes":"","entity":{"slug":"beta-glucan","display_name":"Beta-glucan","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Below a certain antibody level almost nothing happened; above it, the drug worked and also caused the infusion reactions.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[bg-p30988115] Immune Pharmacodynamic Responses of the Novel Cancer Immunotherapeutic Imprime PGG in Healthy Volunteers. (2019). https://pubmed.ncbi.nlm.nih.gov/30988115/ DOI: 10.4049/jimmunol.1801533","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Peripheral blood","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"biomarker_context","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"1d39d600-8f3e-59fc-8cda-7b6316772e65","evidence_kind":"source_excerpt","locator":"Lines 281-292","start_line":281,"end_line":292,"excerpt":"### bg-antibody-level-gates-the-response\nAt the end of infusion free serum antibody levels decreased, circulating immune complex levels increased and complement activation was observed, at approximately 1 to 4 hours after end of infusion increased expression of cytokines and chemokines, a 1.5 to 4-fold increase in neutrophil and monocyte counts and a broad activation of innate immune genes were observed, low-antibody subjects with levels below 20 micrograms per millilitre typically showed minimal changes except when their levels rose above 20 micrograms per millilitre after repeated dosing, mild-to-moderate infusion-related reactions occurred in subjects with antibody at or above 20 micrograms per millilitre, and premedications alleviated some of the infusion-related reactions but also inhibited cytokine responses.\nCondition category: biomarker_context\nnutrient_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.\nplain_language: Below a certain antibody level almost nothing happened; above it, the drug worked and also caused the infusion reactions.\norganism: Human\ntissue_or_cell_type: Peripheral blood\nexperimental_model: Single and multiple intravenous infusions in healthy volunteers stratified by pre-treatment antibody level, with and without premedication\nlimitations: Healthy volunteers and pharmacodynamic endpoints only. Nothing here measures a tumour outcome, so the antibody strata are not validated treatment-selection thresholds.\nexposure: Imprime PGG 4 milligrams per kilogram intravenously, with antihistamine and corticosteroid premedication in some subjects\nevidence_span: {\"source_cache\": \"artifacts/glucan-research/30988115.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d\", \"start_char\": 0, \"end_char\": 1787, \"text_sha256\": \"bd9bd1b314472b30b2e3513ecb5e048178de145217473fa87379e0977d21f90d\"}\n[bg-p30988115] Immune Pharmacodynamic Responses of the Novel Cancer Immunotherapeutic Imprime PGG in Healthy Volunteers. (2019). https://pubmed.ncbi.nlm.nih.gov/30988115/ DOI: 10.4049/jimmunol.1801533","model_system":"Single and multiple intravenous infusions in healthy volunteers stratified by pre-treatment antibody level, with and without premedication","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [bg-p30988115] Immune Pharmacodynamic Responses of the Novel Cancer Immunotherapeutic Imprime PGG in Healthy Volunteers. (2019). https://pubmed.ncbi.nlm.nih.gov/30988115/ DOI: 10.4049/jimmunol.1801533","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"74dc223d-8289-57bf-a731-d220fa017c1e","stable_key":"import-10629adf-a816-5b7b-82db-a76bfbb946f2","title":"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)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"7c62f2d2f8d99b650e6dc26a505b0f053ae1c8bdb38099d4dfc0771f65287461","revision_id":"a53bb794-0a4b-525d-9cf7-22b46a5403b0","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}