Antigenic changes in human albumin caused by reactivity with the occupational allergen diphenylmethane diisocyanate

Anal Biochem. 2010 May 15;400(2):251-8. doi: 10.1016/j.ab.2010.01.037. Epub 2010 Feb 1.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Allergens / chemistry*
  • Amino Acid Sequence
  • Binding Sites
  • Chromatography, High Pressure Liquid / methods*
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Immunoglobulin G / chemistry
  • Immunoglobulin G / metabolism
  • Isocyanates / chemistry*
  • Lysine / chemistry
  • Molecular Sequence Data
  • Occupational Exposure
  • Peptides / analysis
  • Serum Albumin / chemistry
  • Serum Albumin / immunology*
  • Serum Albumin / metabolism
  • Tandem Mass Spectrometry / methods*

Substances

  • Allergens
  • Immunoglobulin G
  • Isocyanates
  • Peptides
  • Serum Albumin
  • 4,4'-diphenylmethane diisocyanate
  • Lysine