CTLA4CT60 gene polymorphism is not associated with differential susceptibility to pemphigus foliaceus

Pemphigus foliaceus is an organ-specific autoimmune disease characterized by autoantibodies against the extracellular region of desmoglein 1, a protein that mediates intercellular adhesion in desmosomes. Cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is a key negative regulator of the T cell immune response, playing an important role in T cell homeostasis and maintenance of peripheral tolerance. Polymorphisms in the CTLA4 gene have been associated with autoimmune diseases and the functional CT60 single nucleotide polymorphism (rs3087243, also named 6230G > A) has been proposed to be a casual variant in several of these diseases. The aim of this study was to ascertain whether this polymorphism is associated with inter-individual variation in susceptibility to pemphigus foliaceus. The population sample in this case-control association study comprised 248 patient and 367 controls. We did not found a significant association of pemphigus foliaceus with the CT60 variants. We conclude that the CTLA4CT60 polymorphism is not an important factor for pemphigus foliaceus pathogenesis in the population analyzed

Activating KIR and HLA Bw4 Ligands Are Associated to Decreased Susceptibility to Pemphigus Foliaceus, an Autoimmune Blistering Skin Disease

The KIR genes and their HLA class I ligands have thus far not been investigated in pemphigus foliaceus (PF) and related autoimmune diseases, such as pemphigus vulgaris. We genotyped 233 patients and 204 controls for KIR by PCR-SSP. HLA typing was performed by LABType SSO reagent kits. We estimated the odds ratio, 95% confidence interval and performed logistic regression analyses to test the hypothesis that KIR genes and their known ligands influence susceptibility to PF. We found significant negative association between activating genes and PF. The activating KIR genes may have an overlapping effect in the PF susceptibility and the presence of more than three activating genes was protective (OR = 0.49, p = 0.003). A strong protective association was found for higher ratios activating/inhibitory KIR (OR = 0.44, p = 0.001). KIR3DS1 and HLA-Bw4 were negatively associated to PF either isolated or combined, but higher significance was found for the presence of both together (OR = 0.34, p<10−3) suggesting that the activating function is the major factor to interfere in the PF pathogenesis. HLA-Bw4 (80I and 80T) was decreased in patients. There is evidence that HLA-Bw4(80T) may also be important as KIR3DS1 ligand, being the association of this pair (OR = 0.07, p = 0.001) stronger than KIR3DS1-Bw4(80I) (OR = 0.31, p = 0.002). Higher levels of activating KIR signals appeared protective to PF. The activating KIR genes have been commonly reported to increase the risk for autoimmunity, but particularities of endemic PF, like the well documented influence the environmental exposure in the pathogenesis of this disease, may be the reason why activated NK cells probably protect against pemphigus foliaceus

Harmful Elements in Estuarine and Coastal Systems

Estuaries and coastal zones are dynamic transitional systems which provide many economic and ecological benefits to humans, but also are an ideal habitat for other organisms as well. These areas are becoming contaminated by various anthropogenic activities due to a quick economic growth and urbanization. This chapter explores the sources, chemical speciation, sediment accumulation and removal mechanisms of the harmful elements in estuarine and coastal seawaters. It also describes the effects of toxic elements on aquatic flora and fauna. Finally, the toxic element pollution of the Venice Lagoon, a transitional water body located in the northeastern part of Italy, is discussed as a case study, by presenting the procedures adopted to measure the extent of the pollution, the impacts on organisms and the restoration activities

Predicting the Proteins of Angomonas deanei, Strigomonas culicis and Their Respective Endosymbionts Reveals New Aspects of the Trypanosomatidae Family

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Endosymbiont-bearing trypanosomatids have been considered excellent models for the study of cell evolution because the host protozoan co-evolves with an intracellular bacterium in a mutualistic relationship. Such protozoa inhabit a single invertebrate host during their entire life cycle and exhibit special characteristics that group them in a particular phylogenetic cluster of the Trypanosomatidae family, thus classified as monoxenics. In an effort to better understand such symbiotic association, we used DNA pyrosequencing and a reference-guided assembly to generate reads that predicted 16,960 and 12,162 open reading frames (ORFs) in two symbiont-bearing trypanosomatids, Angomonas deanei (previously named as Crithidia deanei) and Strigomonas culicis (first known as Blastocrithidia culicis), respectively. Identification of each ORF was based primarily on TriTrypDB using tblastn, and each ORF was confirmed by employing getorf from EMBOSS and Newbler 2.6 when necessary. The monoxenic organisms revealed conserved housekeeping functions when compared to other trypanosomatids, especially compared with Leishmania major. However, major differences were found in ORFs corresponding to the cytoskeleton, the kinetoplast, and the paraflagellar structure. The monoxenic organisms also contain a large number of genes for cytosolic calpain-like and surface gp63 metalloproteases and a reduced number of compartmentalized cysteine proteases in comparison to other TriTryp organisms, reflecting adaptations to the presence of the symbiont. The assembled bacterial endosymbiont sequences exhibit a high A+T content with a total of 787 and 769 ORFs for the Angomonas deanei and Strigomonas culicis endosymbionts, respectively, and indicate that these organisms hold a common ancestor related to the Alcaligenaceae family. Importantly, both symbionts contain enzymes that complement essential host cell biosynthetic pathways, such as those for amino acid, lipid and purine/pyrimidine metabolism. These findings increase our understanding of the intricate symbiotic relationship between the bacterium and the trypanosomatid host and provide clues to better understand eukaryotic cell evolution.84Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)ERC AdG SISYPHEFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq