Antigen-specific stimulation of histamine releasing factors in diisocyanate-induced occupational asthma.

Abstract

Diisocyanate-induced asthma differs from occupational asthma (OA) caused by protein allergens in that specific IgE antibody responses are rarely identified. To investigate the immunopathogenesis of diisocyanate asthma, diisocyanate-exposed workers were evaluated for in vitro production of antigen-specific mononuclear cell-derived histamine releasing factor (HRF). The mean HRF response to diisocyanate-HSA antigens was significantly greater in patients with OA than in diisocyanate-exposed asymptomatic subjects (p < 0.05). No association was found between HRF and diisocyanate-specific antibodies. Analysis of HRF production by subpopulations of peripheral blood mononuclear cells (PBMC) showed that lymphocytes and adherent cells were major sources of both spontaneous and antigen-stimulated HRF. The results suggest that antigen-specific HRF produced by PBMCs are an important biomarker for diisocyanate-induced asthma. This is the first report of hapten-specific stimulation of PBMCs resulting in HRF production.

Indirect assessment of 4,4?-diphenylmethane diisocyanate (MDI) exposure by evaluation of specific humoral immune responses to MDI conjugated to human serum albumin

“…Several previous studies have found no association between elevated levels of specific IgG antibodies to the MDI-HSA antigen, and confirmed OA [ZammitTabona et al, 1983;Tse et al, 1985;Herd and Bernstein, 1994;Lummus et al, 1996]. In this investigation, three workers with an increased IgG antibody level were symptomatic, three were asymptomatic, and none had symptoms suggestive of hypersensitivity pneumonitis.…”

“…Considerable evidence exists indicating that workers with IgG or IgE antibodies specific for one diisocyanate-HSA conjugate exhibit cross-reactivity to antigens prepared with other diisocyanates, to which there have been no workplace exposures [O'Brien et al, 1979;Baur, 1983;Baur and Fruhman, 1981;Malo et al, 1983]. A recent study of workers with confirmed diisocyanate-induced asthma found that diisocyanate-HSA antigens stimulated the production of histamine releasing factor (HRF) by the peripheral blood mononuclear cells [Herd and Bernstein, 1994]. The presence of IgE or IgG antibodies did not correlate with HRF activity, nor with a diagnosis of OA.…”

Pathogenesis of occupational asthma: Table 1

“…In addition, when haptenspecific proliferative response is present, its magnitude is significantly smaller than that induced by common inhalant allergens [108]. In vitro experiments have also reported that PBMCs of workers with diisocyanate-induced OA demonstrate a hapten-specific production of histamine-releasing factor [112,113] and the release of monocyte chemoattractant protein-1, interleukin (IL)-8, tumour necrosis factor (TNF)-a, and interferon (IFN)-c [114]. However, it remains to be established whether LMW agents are capable of inducing a direct, IgE-independent, hapten-specific activation of PBMCs.…”

Human Leukocyte Antigen Associations in Occupational Asthma Induced by Isocyanates

“…Positive skin-prick tests, specific IgE, and IgG have been shown to be present mainly in atopic subjects sensitized to high-molecular-weight sensitizing agents (29), but also in some subjects sensitized to low-molecular-weight agents (e.g., anhydrides, platinum salts, nickel, plicatic acid, and isocyanates) (30)(31)(32)(33)(34). In subjects with occupational asthma induced by both high-and low-molecular-weight compounds, specific immunoglobulins (IgE, IgG) may be found (30)(31)(32)(33)(34). Skin tests and specific antibodies may, therefore, be helpful in the diagnosis of occupational asthma due to high-molecular-weight compounds (35).…”