Diisocyanate Antigen-stimulated Monocyte Chemoattractant Protein-1 Synthesis Has Greater Test Efficiency than Specific Antibodies for Identification of Diisocyanate Asthma

Abstract

We previously reported that diisocyanate-human serum albumin (DIISO-HSA) stimulated production of monocyte chemoattractant protein-1 (MCP-1) by peripheral blood mononuclear cells is significantly associated with a clinical diagnosis of diisocyanate asthma (DA). Others have reported that antibodies for DIISO-HSA are specific but insensitive markers of DA. This study was performed to evaluate test characteristics of the in vitro MCP-1 assay compared with DIISO-HSA-specific immunoglobulin (Ig) G and IgE in identifying workers with DA. MCP-1 was quantitated in peripheral blood mononuclear cell supernatants 48 hours after incubation with DIISO-HSA antigens. Assay results were compared with outcomes of specific inhalation challenge (SIC) testing. Nineteen of 54 (35%) workers assayed for antibodies and MCP-1 stimulation had SIC-confirmed DA. Mean MCP-1 produced by SIC-positive workers was greater than SIC-negative workers (p < or = 0.001). Diagnostic sensitivity, specificity, and test efficiency for specific IgG were 47%, 74%, and 65%, respectively, and for specific IgE were 21%, 89%, and 65%, respectively. Sensitivity, specificity, and test efficiency of the MCP-1 test were 79%, 91%, and 87%, respectively. This study indicates that the MCP-1 stimulation assay has greater sensitivity and specificity than the specific antibody assays in correctly identifying DA.

Human innate immune responses to hexamethylene diisocyanate (HDI) and HDI–albumin conjugates

“…further demonstrated that isocyanatealbumin induced in vitro MCP-1 production by PBMCs was associated with clinical responses to inhalation challenge tests. 15 The present data suggest chemokine responses represent part of a much broader cellular reaction triggered by isocyanate, which may contribute to the chemical's potent (hyper)sensitizing capability.…”

“…4,7 Instead, limited recent studies suggest that human monocyte responses may play an important role in clinical isocyanate exposure outcome. 15,16 Monocytes are crucial cells of the innate arm of the immune system that circulate in an immature form, and differentiate into "tissue macrophages", dendritic cells and alveolar macrophages. [17][18][19][20] Monocytes possess the capacity to modulate immune responses by secreting chemokines and processing/presenting exogenous and "self" antigens.…”

An ATS/ERS report: 100 key questions and needs in occupational asthma

“…Monocyte chemoattractant protein (MCP)-1 seems to be a specific and sensitive tool in the diagnosis of OA due to isocyanates [42]. What is the validity of MCP-1 assessment in OA due to other agents besides isocyanates?…”

Diagnosing occupational asthma: how, how much, how far?: Table 1

“…to complex (unconjugate) platinum salts, trimellitic and acid anhydrides [18,19]. In the case of LMW compounds, particularly some of the most common causes of OA, like isocyanates, the sensitivity and specificity of tests assessing the IgE response is variable, being good for some [20] and less satisfactory for others [21,22]. It is also worth noting that results of both skin and in-vitro tests of IgE-mediated sensitivity may fall to a level below detection when workers are removed from exposure [12].…”

“…An increased CD69 expression on peripheral blood eosinophils after specific inhalation challenge with LMW compounds has been described [25]. Recently, an in-vitro assay measuring production of the C-C chemokine monocyte chemotactic protein (MCP)-1 by peripheral mononuclear cells after 48 h of stimulation with diisocyanate/human serum albumin (HSA) reported 79% sensitivity and 91% specificity in identifying workers with SIC-confirmed OA [22]. At present, however, such techniques are used as research tools and not for clinical practice.…”