HLA-DRB1 association with Henoch-Schonlein purpura

Objective: Henoch-Schönlein purpura (HSP) is the most common vasculitis in children but it is not exceptional in adults. Increased familial occurrence supports a genetic predisposition for HSP. In this context, an association with the human leukocyte antigen-HLA-DRB1*01 phenotype has been suggested in Caucasian individuals with HSP. However, data on the potential association of HSP with HLA-DRB1*01 were based on small case series. To further investigate this issue, we performed HLA-DRB1 genotyping of the largest series of HSP patients ever assessed for genetic studies in Caucasians. Methods: 342 Spanish patients diagnosed with HSP fulfilling the American College of Rheumatology and the Michel et al classification criteria, and 303 sex and ethnically matched controls were assessed. HLA-DRB1 alleles were determined using a PCR-Sequence-Specific-Oligonucleotide Probe (PCR-SSOP) method. Results: A statistically significant increase of HLA-DRB1*01 in HSP patients when compared with controls was found (43% vs 7%, respectively; p<0.001; odds ratio-OR=2.03 [1.43-2.87]). It was due to the increased frequency of HLA-DRB1*0103 phenotype in HSP (14% vs 2%; p<0.001; OR=8.27 [3.46-23.9]). These results remained statistically significant after adjusting for Bonferroni correction. In contrast, a statistically significant decreased frequency of the HLA-DRB1*0301 phenotype was observed in patients compared to controls (5.6% vs 18.1%, respectively; p<0.001, OR=0.26 [0.14-0.47]), even after adjustment for Bonferroni correction. No HLA-DRB1 association with specific features of the disease was found. Conclusion: Our study confirms an association of HSP with HLA-DRB1*01 in Caucasians. Also, a protective effect against the development of HSP appears to exist in Caucasians carrying the HLA-DRB1*03 phenotype

Imaging social and environmental factors as modulators of brain dysfunction: time to focus on developing, non-Western societies

Social and environmental factors are known risk factors and modulators of mental health disorders. We here conducted a nonsystematic review of the neuroimaging literature studying the effects of poverty, urbanicity, and community violence, highlighting the opportunities of studying non-Western developing societies such as those in Latin America. Social and environmental factors in these communities are widespread and have a large magnitude, as well as an unequal distribution, providing a good opportunity for their characterization. Studying the effect of poverty in these settings could help to explore the brain effect of economic improvements, disentangle the effect of absolute and relative poverty, and characterize the modulating impact of poverty on the underlying biology of mental health disorders. Exploring urbanicity effects in highly unequal cities could help identify the specific factors that modulate this effect as well as examine a possible dose–response effect by studying megacities. Studying brain changes in those living among violence, which is particularly high in places such as Latin America, could help to characterize the interplay between brain predisposition and exposure to violence. Furthermore, exploring the brain in an adverse environment should shed light on the mechanisms underlying resilience. We finally provide examples of two methodological approaches that could contribute to this field, namely a big cohort study in the developing world and a consortium-based meta-analytic approach, and argue about the potential translational value of this research on the development of effective social policies and successful personalized medicine in disadvantaged societies.Fil: Crossley, Nicolas A.. Pontificia Universidad Católica de Chile; ChileFil: Alliende, Luz Maria. Pontificia Universidad Católica de Chile; ChileFil: Ossandon, Tomas. Pontificia Universidad Católica de Chile; ChileFil: Castañeda, Carmen Paz. Instituto Psiquiátrico Dr. José Horwitz Barak; ChileFil: González Valderrama, Alfonso. Instituto Psiquiátrico Dr. José Horwitz Barak; Chile. Universidad Finis Terrae.; ChileFil: Undurraga, Juan. Universidad del Desarrollo; Chile. Instituto Psiquiátrico Dr. José Horwitz Barak; ChileFil: Castro, Mariana Nair. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Guinjoan, Salvador Martín. Universidad de Buenos Aires. Facultad de Medicina; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Díaz Zuluaga, Ana M.. Universidad de Antioquia; ColombiaFil: Pineda-Zapata, Julián A.. Instituto de Alta Tecnología Médica; ColombiaFil: López-Jaramillo, Carlos. Hospital Universitario San Vicente Fundación; Colombia. Universidad de Antioquia; ColombiaFil: Reyes Madrigal, Francisco. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: León-Ortíz, Pablo. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: de la Fuente-Sandoval, Camilo. Instituto Nacional de Neurología y Neurocirugía; MéxicoFil: Czepielewski, Leticia Sanguinetti. Hospital de Clinicas de Porto Alegre; BrasilFil: Gama, Clarissa S.. Hospital de Clinicas de Porto Alegre; BrasilFil: Zugman, Andre. Universidade Federal de Sao Paulo; BrasilFil: Gadelha, Ary. Universidade Federal de Sao Paulo; BrasilFil: Jackowski, Andrea. Universidade Federal de Sao Paulo; BrasilFil: Bressan, Rodrigo. Universidade Federal de Sao Paulo; Brasi

Solution structure of the hypothetical protein TA0095 from Thermoplasma acidophilum: A novel superfamily with a two-layer sandwich architecture

TA0095 is a 96-residue hypothetical protein from Thermoplasma acidophilum that exhibits no sequence similarity to any protein of known structure. Also, TA0095 is a member of the COG4004 orthologous group of unknown function found in Archaea bacteria. We determined its three-dimensional structure by NMR methods. The structure displays an α/β two-layer sandwich architecture formed by three α-helices and five β-strands following the order β1-α1-β2-β3-β4-β5-α2-α3. Searches for structural homologs indicate that the TA0095 structure belongs to the TBP-like fold, constituting a novel superfamily characterized by an additional C-terminal helix. The TA0095 structure provides a fold common to the COG4004 proteins that will obviously belong to this new superfamily. Most hydrophobic residues conserved in the COG4004 proteins are buried in the structure determined herein, thus underlying their importance for structure stability. Considering that the TA0095 surface shows a large positively charged patch with a high degree of residue conservation within the COG4004 domain, the biological function of TA0095 and the rest of COG4004 proteins might occur through binding a negatively charged molecule. Like other TBP-like fold proteins, the COG4004 proteins might be DNA-binding proteins. The fact that TA0095 is shown to interact with large DNA fragments is in favor of this hypothesis, although nonspecific DNA binding cannot be ruled out