Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker

Abstract

Use of Hexyl Isocyanate Antigen to Detect Antibodies to Hexamethylene Diisocyanate (HDI) in Sensitized Guinea Pigs and in a Sensitized Worker. Karol, M.H. and Hauth, B.A. (1982). Fundam. Appl. ToxicoL 2:108-113. Hypersensitivity to hexamethylene diisocyanate (HDI) has been reported following occupational exposure. Diagnosis of sensitivity is usually made from clinical evaluation of symptomatology. An in vitro serologic assay for HDI sensitivity was developed by immunizing guinea pigs with HDI and with hexyl isocyanate (HMI). Animals injected intradermally with HMI produced hapten-specific antibodies whereas guinea pigs injected with HDI produced antibodies specific for larger determinants which included the HDI hapten. The larger determinants were assumed to be composed of portions of "self" molecules which reacted in vivo with HDI. Serum albumin appeared to be one such molecule. No cross reactions were noted between antibodies to HDI and another widely used industrial isocyanate, toluene diisocyanate (TDI). Antigens effective in detecting antibodies to HDI or HMI were tested for ability to detect reaginic antibodies in a worker with clinical "HDI" asthma. Using a radioimmunoassay (RAST), antibodies reacted with conjugates containing either HDI or HMI as haptens. In addition, the prevalence of HDI polyisocyanates (Desmodur N) in spray paints prompted its use as a hapten. Antibodies reacted with Desmodur N antigen conjugates in RAST. RAST inhibition further indicated that Desmodur N antigen reacted more readily with the patient's antibodies than did HDI or HMI antigens. These results suggest that the patient may have been exposed to HDI polyisocyanates in spray paint application. Use of Rast inhibition for diagnosis of sensitivity may indicate the precise sensitizing agent within a mixture.

Isocyanate vapor-induced antigenicity of human albumin

“…22 Briefly, duplicate samples of protein in 0.5-mol/L borate-KCl, pH 9.4, were mixed with 50 lL 0.3-mol/L 2,4,6-trinitrobenzenesulfonic acid (Sigma) for 30 minutes at room temperature and analyzed at 420 nm. After subtraction of background, the percent substitution was calculated as 100 3 (1 e [absorbance of HDI exposed albumin/ absorbance of mock exposed albumin]).…”

“…The molar ratio of HDI to albumin was deduced on the basis of the predicted 59 lysine residues in albumin as described. 22 …”

“…This ratio is far lower than the substitution ratios (when reported) for isocyanate-albumin conjugates used in the majority of human immunology studies to date. 9,17,19,22,[30][31][32][33][34] MALDI-MS analysis of vapor-exposed albumin…”

Biophysical determinants of toluene diisocyanate antigenicity associated with exposure and asthma

“…[3][4][5][6][7][8][9][10] A leading hypothesis is that the chemical acts as a hapten and undergoes nucleophilic addition reactions (conjugates) in vivo with airway proteins. 8,11 Strong evidence exists that albumin is the major carrier, 12,13 and that reaction products between isocyanate and albumin include ''neo-epitopes,'' a wide range of which may be possible depending upon the microenvironment. 9,14 The structure of isocyanate-albumin conjugates that form in vivo in human beings, and which might elicit a pathogenic immune response, remains unknown and is critical to defining the primary events in the development of isocyanate asthma.…”

Immunological evaluation of four arc welders exposed to fumes from ignited polyurethane (isocyanate) foam: Antibodies and immune profiles

“…Symptoms following acute and chronic exposure include irritation of the mucous membranes of the eyes, nose, and throat; cough; dyspnea; headaches; and respiratory sensitization. IgE and IgG antibodies to NADs of isocyanates have been found in individuals with hypersensitivity to isocyanates (Bascom et al, 1985;Grunewalder and Karol, 1986;Karol and Hauth, 1982;Karol, 1985Karol, , 1986Pezzini et al, 1984;Zeiss, 1985). Although both acute and delayed sensitization have been demonstrated in these subjects, research into either changes or modulations in cell-mediated immunity (CMI) has been limited to lymphocyte transformation in sensitized individuals and changes in cyclic AMP (Avery et al, 1969;Bruckner et al, 1969;Butcher et al, 1976Butcher et al, , 1982.…”