Historical Archaeology in the Iberian Peninsula

UID/HIS/04209/2019 DL 57/2016/CP1453/CT0084authorsversionpublishe

The TT Genotype of the STAT4 rs7574865 Polymorphism Is Associated with High Disease Activity and Disability in Patients with Early Arthritis

[Background] The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis. [Methodology and Results] We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype. [Conclusions] Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability.This work was partially supported by the RETICS (Redes Tematicas de Investigación Cooperativa, Cooperative Research Thematic Networks) Program, RD08/0075 (RIER) and FIS (Fondo de Investigación en Salud) Health Research Fund grant FIS 08/0754 to IG-A from Instituto de Salud Carlos III (ISCIII; www.isciii.es) and by grants from the European Innovative Medicines Initiative and BTCure Program (http://www.life-sciences-europe.com/orga​nisation/btcure-project-imi-efpia-201103​-innovative-medicines-initiative-2001-28​657.html). The work of IG-A was in part supported by a Research Intensification Grant from the National Health Care System (Instituto Carlos III; www.isciii.es), Madrid, Spain

IFNL4 ss469415590 polymorphism is associated with unfavourable clinical and immunological status in HIV-infected individuals

AbstractThe IFNL4 ss469415590 polymorphism, in high linkage disequilibrium with the IL28B rs12979860 variant, has been associated with hepatitis C virus clearance. We evaluated whether ss469415590 is associated with clinical and immunovirological parameters in human immunodeficiency virus-infected subjects. We found an independent association of the IFNL4 ss469415590 polymorphism with higher prevalence of AIDS-defining illnesses and lower CD4 T cell numbers. These results suggest the existence of common host defence mechanisms against different viral infections

A replication study confirms the association of TNFSF4 (OX40L) polymorphisms with systemic sclerosis in a large European cohort

<p><b>Objectives</b> The aim of this study was to confirm the influence of TNFSF4 polymorphisms on systemic sclerosis (SSc) susceptibility and phenotypic features.</p> <p><b>Methods</b> A total of 8 European populations of Caucasian ancestry were included, comprising 3014 patients with SSc and 3125 healthy controls. Four genetic variants of TNFSF4 gene promoter (rs1234314, rs844644, rs844648 and rs12039904) were selected as genetic markers.</p> <p><b>Results</b> A pooled analysis revealed the association of rs1234314 and rs12039904 polymorphisms with SSc (OR 1.15, 95% CI 1.02 to 1.31; OR 1.18, 95% CI 1.08 to 1.29, respectively). Significant association of the four tested variants with patients with limited cutaneous SSc (lcSSc) was revealed (rs1234314 OR 1.22, 95% CI 1.07 to 1.38; rs844644 OR 0.91, 95% CI 0.83 to 0.99; rs844648 OR 1.10, 95% CI 1.01 to 1.20 and rs12039904 OR 1.20, 95% CI 1.09 to 1.33). Association of rs1234314, rs844648 and rs12039904 minor alleles with patients positive for anti-centromere antibodies (ACA) remained significant (OR 1.23, 95% CI 1.10 to 1.37; OR 1.12, 95% CI 1.01 to 1.25; OR 1.22, 95% CI 1.07 to 1.38, respectively). Haplotype analysis confirmed a protective haplotype associated with SSc, lcSSc and ACA positive subgroups (OR 0.88, 95% CI 0.82 to 0.96; OR 0.88, 95% CI 0.80 to 0.96; OR 0.86, 95% CI 0.77 to 0.97, respectively) and revealed a new risk haplotype associated with the same groups of patients (OR 1.14, 95% CI 1.03 to 1.26; OR 1.20, 95% CI 1.08 to 1.35; OR 1.23, 95% CI 1.07 to 1.42, respectively).</p> <p><b>Conclusions</b> The data confirm the influence of TNFSF4 polymorphisms in SSc genetic susceptibility, especially in subsets of patients positive for lcSSc and ACA.</p&gt

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

Guide to the alien and invasive species of rivers, lakes and estuaries in the Iberian Peninsula.

Guide to the alien and invasive species of rivers, lakes and estuaries in the Iberian Peninsula

Vaginal neutrophil infiltration is contingent on ovarian cycle phase and independent of pathogen infection

The mucosa of the female reproductive tract must reconcile the presence of commensal microbiota and the transit of exogenous spermatozoa with the elimination of sexually transmitted pathogens. In the vagina, neutrophils are the principal cellular arm of innate immunity and constitute the first line of protection in response to infections or injury. Neutrophils are absent from the vaginal lumen during the ovulatory phase, probably to allow sperm to fertilize; however, the mechanisms that regulate neutrophil influx to the vagina in response to aggressions remain controversial. We have used mouse inseminations and infections of Neisseria gonorrhoeae, Candida albicans, Trichomonas vaginalis, and HSV-2 models. We demonstrate that neutrophil infiltration of the vaginal mucosa is distinctively contingent on the ovarian cycle phase and independent of the sperm and pathogen challenge, probably to prevent sperm from being attacked by neutrophils. Neutrophils extravasation is a multi-step cascade of events, which includes their adhesion through selectins (E, P and L) and integrins of the endothelial cells. We have discovered that cervical endothelial cells expressed selectin-E (SELE, CD62E) to favor neutrophils recruitment and estradiol down-regulated SELE expression during ovulation, which impaired neutrophil transendothelial migration and orchestrated sperm tolerance. Progesterone up-regulated SELE to restore surveillance after ovulation