A functional PTPN22 polymorphism associated with several autoimmune diseases is not associated with IgA deficiency in the Spanish population

BACKGROUND: The 1858C/T SNP of the PTPN22 gene has been associated with many autoimmune diseases, suggesting the existence of an inflammatory process common to all of them. We studied the association of that polymorphism with immunoglobulin A deficiency (IgAD) following a double approach: a case-control and a TDT study. METHODS: A total of 259 IgAD patients and 455 unrelated matched controls, and 128 families were used for each approach. Comparisons were performed using Chi-Square tests or Fisher's exact test when necessary. RESULTS: No association between the PTPN22 1858C/T SNP and IgA deficiency was found in any case (allelic frequencies 8% vs. 6% in patients and controls, respectively, OR= 1.14 (0.72–1.79), p= 0.56; TDT p = 0.08). CONCLUSION: The result obtained seems to reinforce the consideration of IgA deficiency as a primary immunodeficiency rather than an autoimmune disease

High-Density SNP Mapping of the HLA Region Identifies Multiple Independent Susceptibility Loci Associated with Selective IgA Deficiency

Selective IgA deficiency (IgAD; serum IgA<0.07 g/l) is the most common form of human primary immune deficiency, affecting approximately 1∶600 individuals in populations of Northern European ancestry. The polygenic nature of IgAD is underscored by the recent identification of several new risk genes in a genome-wide association study. Among the characterized susceptibility loci, the association with specific HLA haplotypes represents the major genetic risk factor for IgAD. Despite the robust association, the nature and location of the causal variants in the HLA region remains unknown. To better characterize the association signal in this region, we performed a high-density SNP mapping of the HLA locus and imputed the genotypes of common HLA-B, -DRB1, and -DQB1 alleles in a combined sample of 772 IgAD patients and 1,976 matched controls from 3 independent European populations. We confirmed the complex nature of the association with the HLA locus, which is the result of multiple effects spanning the entire HLA region. The primary association signal mapped to the HLA-DQB1*02 allele in the HLA Class II region (combined P = 7.69×10−57; OR = 2.80) resulting from the combined independent effects of the HLA-B*0801-DRB1*0301-DQB1*02 and -DRB1*0701-DQB1*02 haplotypes, while additional secondary signals were associated with the DRB1*0102 (combined P = 5.86×10−17; OR = 4.28) and the DRB1*1501 (combined P = 2.24×10−35; OR = 0.13) alleles. Despite the strong population-specific frequencies of HLA alleles, we found a remarkable conservation of these effects regardless of the ethnic background, which supports the use of large multi-ethnic populations to characterize shared genetic association signals in the HLA region. We also provide evidence for the location of association signals within the specific extended haplotypes, which will guide future sequencing studies aimed at characterizing the precise functional variants contributing to disease pathogenesis

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

Spinosad bait sprays against the olive fruit fly ( Bactrocera oleae

Abundance and diversity of arthropods were compared in olive trees treated against the olive fruit fly with spinosad bait sprays and an untreated control, paying special attention to predators and parasitoids. Spinosad bait sprays did not reduce the abundance and diversity of arthropods as a whole in the canopy. However, principal response curve analysis revealed a significant deleterious effect of the treatments on natural enemies in the last of the three years of study. The most affected taxa were Anthocoridae (especially Orius spp.) and Aphelinidae. © 2014 Taylor & Francis

Association between heavy metal and metalloid levels in topsoil and cancer mortality in Spain

Spatio-temporal cancer mortality studies in Spain have revealed patterns for some tumours which display a distribution that is similar across the sexes and persists over time. Such characteristics would be common to tumours that shared risk factors, including the geochemical composition of the soil. The aim of this study was to assess the possible association between heavy metal and metalloid levels in topsoil (upper soil horizon) and cancer mortality in mainland Spain. Ecological cancer mortality study at a municipal level, covering 861,440 cancer deaths (27 different tumour locations) in 7917 Spanish mainland towns, from 1999 to 2008. The elements included in this analysis were Al, As, Cd, Cr, Cu, Fe, Mn, Ni, Pb and Zn. Topsoil levels (partial extraction) were determined by ICP-MS at 13,317 sampling points. For the analysis, the data on the topsoil composition have been transformed by the centred logratio (clr-transformation). Principal factor analysis was performed to obtain independent latent factors for the transformed variables. To estimate the effect of heavy metal levels in topsoil composition on mortality, we fitted Besag, York and Mollié models, which included each town's factor scores as the explanatory variable. Integrated Nested Laplace Approximation (INLA) was used as a tool for Bayesian inference. All results were adjusted for sociodemographic variables. The results showed an association between trace contents of heavy metals and metalloids in topsoil and mortality due to tumours of the digestive system in mainland Spain. This association was observed in both sexes, something that would support the hypothesis that the incorporation of heavy metals into the trophic chain might be playing a role in the aetiology of some types of cancer. Topsoil composition and the presence of potentially toxic elements in trace concentrations might be an additional component in the aetiology of some types of cancer, and go some way to determine the ensuing geographic differences in mortality in Spain. The results support the interest of inclusion of heavy metal levels in topsoil as a hypothesis in analytical epidemiological studies using biological markers of exposure to heavy metals and metalloids.The study was partially supported by research grants from the Carlos III Institute of Health (PI4CIII/50) and Spanish Health Research Fund (FIS PI11/00871 and FIS CP11/00112). Mortality data were supplied by the Spanish National Statistics Institute in accordance with a specific confidentiality protocol.S