Is occupational asthma to diisocyanates a non-IgE-mediated disease?

BACKGROUND: Exposure to diisocyanates in the workplace is an important cause of occupational asthma. The majority of patients with diisocyanate-induced asthma have no detectable diisocyanate-specific IgE antibodies in serum. There has been much debate as to whether this is due to diisocyanate-induced asthma being mediated by non-IgE mechanisms or whether it is the result of using inappropriate conjugates. OBJECTIVE: We sought to determine whether RNA message for Cepsilon, IL-4, and other associated inflammatory markers could be detected locally within the bronchial mucosa after diisocyanate challenge. METHODS: Fiberoptic bronchoscopic bronchial biopsy specimens were obtained at 24 hours after both a control and an active challenge in 5 patients with positive and 7 patients with negative inhalation test responses to diisocyanates. Using both immunohistochemistry and in situ hybridization, we determined mRNA for Cepsilon, IL-4, IL-5, and other associated inflammatory markers. RESULTS: There was a striking absence of Cepsilon and IL-4 mRNA-positive cells in bronchial biopsy specimens from patients challenged with diisocyanate (Cepsilon median of 0 and interquartile range of 0-1.85; IL-4 median of 0 and interquartile range of 0-0.85). In contrast, there were increased numbers of IL-5-, CD25-, and CD4-positive cells and a trend toward an increase in eosinophils after active challenge with diisocyanate. CONCLUSION: We found a striking absence of both bronchial Cepsilon and IL-4 RNA message after inhalation challenge with diisocyanates, irrespective of whether the challenge test response was positive or negative. We propose that diisocyanate-induced asthma is a non-IgE-mediated disease, at least in patients in whom specific IgE antibodies to diisocyanates are undetectable.     

ELISPOT analysis of a new CTL based DNA vaccine for HIV-1 using GM-CSF in DNA prime/peptide boost strategy: GM-CSF induced long-lived memory responses

Genetic adjuvants have potential role in improvement of immune responses against DNA vaccines. GM-CSF as a genetic adjuvant can recruit and augment dendritic cell numbers in the site of immune responses and thereby induce cellular and humoral immune responses. Here we show that co-immunization of a DNA vaccine from HIV-1P24-Nef with GM-CSF in DNA priming and peptide boost strategy increases the immunogenicity of our candidate vaccine. Analysis of immune response shows that co-immunization with GM-CSF boosts cellular immune responses through increasing proliferation activity and CTL function. Results of cytokine profile studies show that both IL-4 and IFN-γ levels were augmented. Also, co-immunization with GM-CSF resulted in a higher level of total IgG, comprising approximately equal levels of both specific IgG1 and IgG2a subtypes. Monitoring of cellular and humoral immune responses for 20 weeks after final immunization revealed the aptitude of GM-CSF for inducing long-lived humoral and cell mediated immune responses. Overall, our results suggest that GM-CSF is able to induce long term memory for the HIV-1 P24-Nef vaccine candidate while the exact mechanisms involved remained to be clarified.     

The severity of coronary atherosclerosis in diabetic and non-diabetic metabolic syndrome patients diagnosed according to different criteria and undergoing elective angiography

Our aim in this study was to evaluate the relationship between metabolic syndrome (MS) as defined by different criteria and the severity of coronary lesions in a sample of diabetic and non-diabetic patients undergoing elective coronary angiography. All patients had blood and urine tests, physical examinations were performed before angiography, and finally they were classified based on three criteria (World Health Organisation-WHO, Adult Treatment Panel-ATP III and International Diabetes Federation-IDF). Eighty-eight patients were diabetic, and 96 patients were non-diabetic. Among all patients, diabetics had significantly higher Gensini scores (P < 0.001). According to WHO criteria (P = 0.005) and IDF criteria (P = 0.015) metabolic syndrome patients had higher Gensini scores, but for ATP III criteria difference was not significant. When we evaluated diabetics and non-diabetics separately, non-diabetic patients with MS had significantly higher scores with WHO definition (P = 0.015) and mildly higher but not significant values with other MS criteria (P = 0.057 for both IDF and ATP III). Neither any one of MS components nor gender revealed significant relationship with coronary disease severity. In our study with a cohort of Turkish patients undergoing elective coronary angiography; we concluded that MS should be taken into consideration, especially in non-diabetic patients.