ABSTRACT
For biomonitoring environmental exposure to acrylonitrile (AN), a monoclonal antibody (mAb) A2D1, was developed to recognize specifically the hemoglobin (Hb) adduct, Hb-AN, but not Hb itself. This appears to be the first example that a small molecule-like AN may introduce new antigenicity into hemoglobin, which already exhibits multiple antigenic determinants. This report addresses the localization of the newly formed antigenic sites in human Hb-AN. As antigenic probes, the AN conjugates of 10 amino acids, six dipeptides, and four tripeptides were prepared as monitored by 1H NMR, and their antigenicity was evaluated by competitive inhibition immunoassay. A Lys-epsilonNH-AN was found essential to inhibiting activity. The potent peptide-AN inhibitors, containing a sequence of His and Lys, showed IC50 at the micromolar concentration, thus implicating human Hbalpha-89,90 and Hbbeta-143,144 in the distal heme pocket region as the new antigenic sites.
Subject(s)
Acrylonitrile/immunology , Hemoglobins/immunology , Lysine/chemistry , Acrylonitrile/chemistry , Acrylonitrile/toxicity , Animals , Antibodies, Monoclonal/chemistry , Antigens/chemistry , Antigens/immunology , Binding, Competitive/drug effects , Environmental Monitoring , Enzyme-Linked Immunosorbent Assay , Hemoglobins/chemistry , Hemoglobins/metabolism , Humans , Immunoassay , Mice , Peptides/chemistry , Peptides/immunology , Peptides/pharmacologyABSTRACT
BACKGROUND: Hemodialysis-associated hypersensitivity reactions are well documented in the literature. Ethylene oxide sensitization and activation of complement are important factors involved during such reactions. The majority of severe hypersensitivity reactions in dialysis patients, however, is due to sensitization to ethylene oxide. METHODS: We report a patient admitted to the hospital with worsening of his renal function. He subsequently required three hemodialysis treatments, all of which resulted in severe hypersensitivity reactions requiring endotracheal intubation. The initial hypersensitivity episode was thought to be due to complement activation to the cupramonium-rayon membrane dialyzer. Despite changing to a polyacrylonitrile membrane, which does not activate complement, a second hypersensitivity reaction developed. Suspecting ethylene oxide hypersensitivity, the third hemodialysis session incorporated a biocompatible dialyzer that was sterilized with gamma irradiation, not ethylene oxide. Yet again, an anaphylactoid reaction resulted. It was postulated that residual ethylene oxide in the tubing might have triggered this last attack. RESULTS: Despite a negative RAST (radioallergosorbent test) to ethylene oxide, the strong history surrounding each of the hypersensitivity episodes and high index of suspicion pointed to ethylene oxide hypersensitivity as the etiologic factor. To this end, the patient fared much better when peritoneal dialysis was initiated. The patient subsequently died from other complications of his illness. CONCLUSIONS: This case report demonstrates both the complex nature involving a hypersensitivity reaction to hemodialysis and the life-threatening severity of such a reaction. Replacing ethylene oxide with steam or gamma radiation to sterilize dialyzers and thoroughly rinsing new dialyzers and tubing with normal saline may help circumvent this problem.
