Serum IgE Reactivity Profiling in an Asthma Affected Cohort

BACKGROUND: Epidemiological evidence indicates that atopic asthma correlates with high serum IgE levels though the contribution of allergen specific IgE to the pathogenesis and the severity of the disease is still unclear. METHODS: We developed a microarray immunoassay containing 103 allergens to study the IgE reactivity profiles of 485 asthmatic and 342 non-asthmatic individuals belonging to families whose members have a documented history of asthma and atopy. We employed k-means clustering, to investigate whether a particular IgE reactivity profile correlated with asthma and other atopic conditions such as rhinitis, conjunctivitis and eczema. RESULTS: Both case-control and parent-to-siblings analyses demonstrated that while the presence of specific IgE against individual allergens correlated poorly with pathological conditions, particular reactivity profiles were significantly associated with asthma (p<10E-09). An artificial neural network (ANN)-based algorithm, calibrated with the profile reactivity data, correctly classified as asthmatic or non-asthmatic 78% of the individual examined. Multivariate statistical analysis demonstrated that the familiar relationships of the study population did not affect the observed correlations. CONCLUSIONS: These findings indicate that asthma is a higher-order phenomenon related to patterns of IgE reactivity rather than to single antibody reactions. This notion sheds new light on the pathogenesis of the disease and can be readily employed to distinguish asthmatic and non-asthmatic individuals on the basis of their serum reactivity profile

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference

Ocular surface and respiratory tract damages from occupational, sub-chronic exposure to fluorspar: case report and other considerations

OBJECTIVES: To report the ocular surface and respiratory tract damages due to a sub-chronic (3 months), occupational exposure to fluorspar dust in case of inconsistent use of personal protective equipment. METHODS: A 50-year-old man was referred to our clinic with bilateral conjunctival injection, ocular foreign body sensation and symptoms of ocular discomfort. He reported having 3 days before an urgent hospital admission for dyspnoea with odynophagia, hyposmia, nausea, vomiting, headache and asthenia. Otorhinolaryngological examination revealed a severe hypertrophic rhinopharyngitis and a significant decrease in overall sensitivity to olfactory stimuli. General anamnesis was negative for previous diseases or medication use. RESULTS: Ocular examination revealed a diffuse injection of the ocular surface with some areas of conjunctival and limbal ischaemia, a best-corrected visual acuity of 20/25 in both eyes, an intraocular pressure of 23 and 21 mmHg, respectively, in the right and in the left eyes, and a normal fundus oculi. Assessment of the tear film and ocular surface showed the presence of dry eye disease. Based on medical history and clinical tests, initial diagnostic hypothesis was ocular surface burn due to chemical exposure, i.e. to fluorspar. Therefore, anterior segment fluorescein angiography was performed to confirm the extension of conjunctival and limbal ischaemia. Thus, ocular ischaemia was detected in approximately 10 clock hours of limbus and in 50% of conjunctiva. CONCLUSIONS: The present work remarks the importance of using protective equipment for preventing ocular and respiratory tract damages in workers occupationally exposed to the 'acid-grade fluorite'