title: Antibodies from a patient with type 1 diabetes and celiac disease bind to macrophages that express the scavenger receptor CD163.
abstract: Antibodies against the wheat storage globulin Glo-3A from a patient with both type 1 diabetes (T1D) and celiac disease were enriched to identify potential molecular mimicry between wheat antigens and T1D target tissues. Recombinant Glo-3A was used to enrich anti-Glo-3A immunoglobulin G antibodies from plasma by batch affinity chromatography. Rat jejunum and pancreas, as well as human duodenum and monocytes were probed, and binding was evaluated by immunohistochemistry and confocal microscopy. Glo-3A-enriched antibodies bound to a specific subset of cells in the lamina propria of rat jejunum that co-localized mostly with a marker of resident, alternatively activated CD163-positive (CD163⁺) macrophages. Blood monocytes and macrophage-like cells in human duodenum were also labelled with the enriched antibodies. Blocking studies revealed that binding to CD163⁺ macrophages was not due to cross-reactivity with anti-Glo-3A antibodies, but rather to non-Glo-3A antibodies co-purified during antibody enrichment. The novel finding of putative autoantibodies against tolerogenic intestinal CD163⁺ macrophages suggests that regulatory macrophages were targeted in this patient with celiac disease and T1D.
authors.affiliation: Chronic Disease Program, Ottowa Hospital Research Institute, Ottowa, Ontario.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Sonier
authors.forename: Alexander
authors.initials: A
authors.lastname: Strom
authors.forename: Gen-Sheng
authors.initials: GS
authors.lastname: Wang
authors.forename: Christopher
authors.initials: C
authors.lastname: Patrick
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Crookshank
authors.forename: Majid
authors.initials: M
authors.lastname: Mojibian
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: MacFarlane
authors.forename: Fraser W
authors.initials: FW
authors.lastname: Scott
mesh_terms: D000818:Animals; D000917:Antibody Formation; D015703:Antigens, CD / Q000378:metabolism*; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism*; D015551:Autoimmunity; D015415:Biomarkers; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism; D016326:Extracellular Matrix Proteins / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007150:Immunohistochemistry; D008264:Macrophages / Q000276:immunology*; D009000:Monocytes / Q000276:immunology; D051381:Rats; D011913:Rats, Inbred BB; D011956:Receptors, Cell Surface / Q000378:metabolism*; D055314:Seed Storage Proteins / Q000276:immunology; D021182:Wheat Hypersensitivity; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D015415:Biomarkers; D000098902:CD163 Antigen; D016326:Extracellular Matrix Proteins; D007074:Immunoglobulin G; D011956:Receptors, Cell Surface; D055314:Seed Storage Proteins; C117904:WG-55 protein, Triticum aestivum