title: Antigenic changes in human albumin caused by reactivity with the occupational allergen diphenylmethane diisocyanate.
abstract: Diphenylmethane diisocyanate (MDI), the chemical commonly used as a cross-linking agent in commercial polyurethane production, is a well-recognized cause of asthma. Reaction products between MDI and "self" proteins are hypothesized to act as antigens capable of inducing airway inflammation and asthma; however, such MDI antigens remain incompletely understood. We used a variety of analytical methods to characterize the range of MDI-albumin reaction products that form under physiological conditions. Sites of MDI conjugation on antigenic MDI-albumin products, as defined by serum immunoglobulin G (IgG) from MDI-exposed workers, were determined by high-performance liquid chromatography (HPLC) followed by tandem mass spectrometry (MS/MS). The data identified 14 MDI conjugation sites (12 lysines and 2 asparagines) on human albumin and highlight reaction specificity for the second lysine in dilysine (KK) motifs, and this may be a common characteristic of "immune-sensitizing" chemicals. Several of the MDI conjugation sites are not conserved in albumin from other species, and this may suggest species differences in epitope specificity for self protein (albumin)-isocyanate conjugates. The study also describes new applications of contemporary proteomic methodology for characterizing and standardizing MDI-albumin conjugates destined for use in clinical research.
authors.affiliation: Department of Internal Medicine, Yale School of Medicine, New Haven, CT 06520, USA. adam.wisnewski@yale.edu
authors.forename: Adam V
authors.initials: AV
authors.lastname: Wisnewski
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.forename: Carrie A
authors.initials: CA
authors.lastname: Redlich
mesh_terms: D000485:Allergens / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism; D017953:Isocyanates / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D008969:Molecular Sequence Data; D016273:Occupational Exposure; D010455:Peptides / Q000032:analysis; D012709:Serum Albumin / Q000737:chemistry / Q000276:immunology* / Q000378:metabolism; D053719:Tandem Mass Spectrometry / Q000379:methods*; D001559:Benzhydryl Compounds
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D017953:Isocyanates; D008239:Lysine; D010455:Peptides; D012709:Serum Albumin; C005969:4,4'-diphenylmethane diisocyanate; D001559:Benzhydryl Compounds