Abstract
PurposeEarly recognition improves the prognosis of isocyanate asthma. A major unanswered question is whether IgE-dependent mechanisms are of diagnostic value? Our objective was to appraise serological methods using various methylenediphenyl diisocyanate (MDI)-albumin conjugates and weigh up the data versus the outcome of standardized comprehensive clinical diagnostics to evaluate the viability of immunological analysis in supportive MDI-asthma diagnosis (OAI).MethodsSpecific IgE (sIgE) and IgG (sIgG) binding was measured with fluorescence enzyme immunoassay in 43 study subjects (using conjugates prepared in-vapor, in-solution and commercial preparations). The differential clinical diagnosis included standardized measurement of pulmonary function, non-specific bronchial hyper-responsiveness, specific MDI-prick test (MDI-SPT) and specific inhalation challenge (MDI-SIC).ResultsDetailed diagnostic scheme allows the differential OAI and MDI-induced hypersensitivity pneumonitis (PI). The presumed OAI diagnoses were confirmed in 84 % (45 % cases having demonstrable sIgE antibodies) with RR 5.7, P > 0.001, when OAI diagnosis is correlated with MDI-SIC/MDI-SPT (RR 1.28 for MDI-SIC alone); sIgG antibodies were clinically relevant for PI and not for the OA diagnosis. MDI-specific IgE data generated with commercial ImmunoCAP preparations show high correlation with our in-vapor generated MDI conjugates.ConclusionsIsocyanate-specific IgE antibodies are not always detectable but their presence is strongly predictive of OAI and supportive for the diagnosis. MDI-SPT can be a valuable parameter differentiating OAI and PI. We have confirmed and extended published data showing that isocyanate-albumin conjugates perform better in specific antibody assays when prepared with volatile phase formulations and would like to stress additionally the necessity for further refinements and standardization in clinical diagnostics procedures.Electronic supplementary materialThe online version of this article (doi:10.1007/s00420-012-0772-6) contains supplementary material, which is available to authorized users.
Highlights
Asthma is generally acknowledged as a critical endpoint after exposure to isocyanates (Malo and Chan-Yeung 2009; Maestrelli et al 2009; Mapp et al 1994), like 4,40-methylenediphenyl diisocyanate (MDI) the most commonly used isocyanate
A major unanswered question is whether IgE-dependent mechanisms are of diagnostic value? Our objective was to appraise serological methods using various methylenediphenyl diisocyanate (MDI)-albumin conjugates and weigh up the data versus the outcome of standardized comprehensive clinical diagnostics to evaluate the viability of immunological analysis in supportive MDI-asthma diagnosis (OAI)
Is it possible that isocyanate asthma has a different etiology from environmental asthma or that the pathophysiological mechanisms are, at least in part, IgE-independent? Or that the IgE antibodies remain undetected because the sampling time is too late after exposure? Or that the available formulations used in the conventional immunological tests are inappropriate? Fundamental to this dilemma is the appropriateness of the isocyanate-protein conjugates used in any antibody detection assays and their relevance to the immunogenic haptenic complexes formed during the pathophysiological conditions
Summary
Asthma is generally acknowledged as a critical endpoint after exposure to isocyanates (Malo and Chan-Yeung 2009; Maestrelli et al 2009; Mapp et al 1994), like 4,40-methylenediphenyl diisocyanate (MDI) the most commonly used isocyanate. Inflamed airways characteristic of asthma may result from an allergic reaction to these conjugates, with the generation of specific IgE antibodies. Isocyanate asthma is expected to be associated with the production of isocyanate-specific IgE antibodies detectable in immunological tests. The existing immunodiagnostic methods detect allergen-specific IgE antibodies mostly in a minority (20–50 %) of the patients suffering from isocyanate asthma (Wisnewski and Jones 2010). Is it possible that isocyanate asthma has a different etiology from environmental asthma or that the pathophysiological mechanisms are, at least in part, IgE-independent? Fundamental to this dilemma is the appropriateness of the isocyanate-protein conjugates used in any antibody detection assays and their relevance to the immunogenic haptenic complexes (or newly formed antigenic determinants) formed during the pathophysiological conditions Is it possible that isocyanate asthma has a different etiology from environmental asthma or that the pathophysiological mechanisms are, at least in part, IgE-independent? Or that the IgE antibodies remain undetected because the sampling time is too late after exposure? Or that the available formulations used in the conventional immunological tests are inappropriate? Fundamental to this dilemma is the appropriateness of the isocyanate-protein conjugates used in any antibody detection assays and their relevance to the immunogenic haptenic complexes (or newly formed antigenic determinants) formed during the pathophysiological conditions
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