BAFF, APRIL and BAFFR on the pathogenesis of Immunoglobulin-A vasculitis

BAFF, APRIL and BAFF-R are key proteins involved in the development of B-lymphocytes and autoimmunity. Additionally, BAFF, APRIL and BAFFR polymorphisms were associated with immune-mediated conditions, being BAFF GCTGT>A a shared insertion-deletion genetic variant for several autoimmune diseases. Accordingly, we assessed whether BAFF, APRIL and BAFFR represent novel genetic risk factors for Immunoglobulin-A vasculitis (IgAV), a predominantly B-lymphocyte inflammatory condition. BAFF rs374039502, which colocalizes with BAFF GCTGT>A, and two tag variants within APRIL (rs11552708 and rs6608) and BAFFR (rs7290134 and rs77874543) were genotyped in 386 Caucasian IgAV patients and 806 matched healthy controls. No genotypes or alleles differences were observed between IgAV patients and controls when BAFF, APRIL and BAFFR variants were analysed independently. Likewise, no statistically significant differences were found in the genotype and allele frequencies of BAFF, APRIL or BAFFR when IgAV patients were stratified according to the age at disease onset or to the presence/absence of gastrointestinal (GI) or renal manifestations. Similar results were disclosed when APRIL and BAFFR haplotypes were compared between IgAV patients and controls and between IgAV patients stratified according to the clinical characteristics mentioned above. Our results suggest that BAFF, APRIL and BAFFR do not contribute to the genetic network underlying IgAV.Acknowledgements: We are indebted to the patients and healthy controls for their essential collaboration to this study. We also thank the National DNA Bank Repository (Salamanca) for supplying part of the control samples. This study was supported by European Union FEDER funds and `Fondo de Investigaciones Sanitarias´ (grant PI18/00042) from ‘Instituto de Salud Carlos III’ (ISCIII, Health Ministry, Spain). DP-P is a recipient of a Río Hortega programme fellowship from the ISCIII, co-funded by the European Social Fund (ESF, `Investing in your future´) (grant number CM20/00006). SR-M is supported by funds of the RETICS Program (RD16/0012/0009) (ISCIII, co-funded by the European Regional Development Fund (ERDF)). VP-C is supported by a pre-doctoral grant from IDIVAL (PREVAL 18/01). BA-M is a recipient of a `López Albo´ Post-Residency Programme funded by Servicio Cántabro de Salud. LL-G is supported by funds from IDIVAL (INNVAL20/06). OG is staff personnel of Xunta de Galicia (Servizo Galego de Saude (SERGAS)) through a research-staff stabilization contract (ISCIII/SERGAS) and his work is funded by ISCIII and the European Union FEDER fund (grant numbers RD16/0012/0014 (RIER) and PI17/00409). He is beneficiary of project funds from the Research Executive Agency (REA) of the European Union in the framework of MSCA-RISE Action of the H2020 Programme, Project 734899—Olive-Net. RL-M is a recipient of a Miguel Servet type I programme fellowship from the ISCIII, cofunded by ESF (`Investing in your future´) (grant number CP16/00033)

Replication of TCF7L2 rs7903146 association with type 2 diabetes in an Iranian population

The transcription factor 7-like 2 gene (TCF7L2) rs7903146 T allele is constantly associated with Type 2 diabetes in various populations and ethnic groups. Nevertheless, this has not been observed in two studies involving Arab populations. The aim of the present study was to investigate the association between TCF7L2 rs7903146 in an Iranian population. Type 2 diabetes patients (N = 258) and normal healthy control subjects (N = 168) from the same area, were examined. The ARMS- PCR (Amplification Refractory Mutation System) technique, subsequently validated by direct sequencing, was used for genotyping. Allele and genotype frequencies were significantly different between patients and controls TT vs. CT + CC [p 0.0081 OR 3.4 95%CI (1.27-11.9)] and T vs. C allele [p 0.02 OR 1.4 95%CI (1.03-1.9)]. Our data thus confirm the association between the rs7903146 T allele and T2D in an Iranian population, contrary to previous reports in Arab populations. This can possibly be attributed to differences in ethnic background or the effects of environmental factors

HIV and HPV infections and ocular surface squamous neoplasia: systematic review and meta-analysis.

BACKGROUND: The frequency of ocular surface squamous neoplasias (OSSNs) has been increasing in populations with a high prevalence of infection with human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) and infection with human papillomavirus (HPV). We aimed to quantify the association between HIV/AIDS and HPV infection and OSSN, through systematic review and meta-analysis. METHODS: The articles providing data on the association between HIV/AIDS and/or HPV infection and OSSN were identified in MEDLINE, SCOPUS and EMBASE searched up to May 2013, and through backward citation tracking. The DerSimonian and Laird method was used to compute summary relative risk (RR) estimates and 95% confidence intervals (95% CI). Heterogeneity was quantified with the I(2) statistic. RESULTS: HIV/AIDS was strongly associated with an increased risk of OSSN (summary RR=8.06, 95% CI: 5.29-12.30, I(2)=56.0%, 12 studies). The summary RR estimate for the infection with mucosal HPV subtypes was 3.13 (95% CI: 1.72-5.71, I(2)=45.6%, 16 studies). Four studies addressed the association between both cutaneous and mucosal HPV subtypes and OSSN; the summary RR estimates were 3.52 (95% CI: 1.23-10.08, I(2)=21.8%) and 1.08 (95% CI: 0.57-2.05, I(2)=0.0%), respectively. CONCLUSION: Human immunodeficiency virus infection increases the risk of OSSN by nearly eight-fold. Regarding HPV infection, only the cutaneous subtypes seem to be a risk factor

Genetic polymorphisms of the RAS-cytokine pathway and chronic kidney disease

Chronic kidney disease (CKD) in children is irreversible. It is associated with renal failure progression and atherosclerotic cardiovascular (CV) abnormalities. Nearly 60% of children with CKD are affected since birth with congenital or inherited kidney disorders. Preliminary evidence primarily from adult CKD studies indicates common genetic risk factors for CKD and atherosclerotic CV disease. Although multiple physiologic pathways share common genes for CKD and CV disease, substantial evidence supports our attention to the renin angiotensin system (RAS) and the interlinked inflammatory cascade because they modulate the progressions of renal and CV disease. Gene polymorphisms in the RAS-cytokine pathway, through altered gene expression of inflammatory cytokines, are potential factors that modulate the rate of CKD progression and CV abnormalities in patients with CKD. For studying such hypotheses, the cooperative efforts among scientific groups and the availability of robust and affordable technologies to genotype thousands of single nucleotide polymorphisms (SNPs) across the genome make genome-wide association studies an attractive paradigm for studying polygenic diseases such as CKD. Although attractive, such studies should be interpreted carefully, with a fundamental understanding of their potential weaknesses. Nevertheless, whole-genome association studies for diabetic nephropathy and future studies pertaining to other types of CKD will offer further insight for the development of targeted interventions to treat CKD and associated atherosclerotic CV abnormalities in the pediatric CKD population

Low-power, deformable, dynamic multicolor electrochromic skin

Active camouflage exhibited by certain creatures in nature such as cephalopods has inspired the fabrication of display devices for human-adaptive camouflage technologies. In order to realize that, electrochromic devices (ECDs) have attracted significant attention owing to their low-voltage operations and fast responses. However, the effective utilization of ECDs requires multicolor patterning, durable functioning, and wearable characteristics, simultaneously, but has not been explored. Here, we demonstrate a low-power, deformable, dynamic multicolor electrochromic skin (DMECS) that mimics the multicolor patterning and the active camouflage functionalities of the skins of cephalopods. The electrochromic polymers such as poly(3-hexylthiophene-2,5-diyl), poly[2-methoxy-5-(2-ethylhexyl-oxy)-1,4-phenylenevinylene], and P4a (green color polymer) are used to create purple, orange, and green colors, respectively. An iontronic polymer pump composed of an ionic liquid (1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) incorporated in thermoplastic polyurethane is used as a deformable and transparent solid-state electrolyte that enables low-voltage (+/- 3 V) operated DMECS with excellent cyclic coloration/bleaching stability (>35,000 s), fast response (similar to 1.75 s), and high durability under repeated 10,000 cycles of compressive force (with a bending radius of 8 mm) and tensile strains (similar to 100% up to 15,000 s). We believe that our DMECS can offer user-controlled selective coloration/bleaching of arbitrary display patterns and open new avenues for next-generation wearable optoelectronics.11Nsciescopu

HLA-DR association in papillary thyroid carcinoma

Abstract. Objective: Papillary thyroid carcinoma (PTC) is the most frequent types of thyroid malignancies. Several genes may be involved in susceptibility of thyroid cancer including Human Leukocyte Antigens (HLA). The association of thyroid carcinoma with HLA alleles has been previously studied in other populations and certain HLA alleles were shown to be either predisposing or protective. The aim of this study was to determine the association between HLA-DR and papillary thyroid carcinoma in an Iranian population. Design: HLA-DR antigen frequencies were determined in patients with papillary thyroid carcinoma (N = 70) and non-related healthy controls (N = 180) using PCR -SSP. Main Outcome: We found that HLA-DRB1*04 frequency was significantly higher in our patients compared to the controls [P = 0.02, OR; 1.9, 95% CI (1.04-3.57)]. Conclusions: Our results revealed HLA-DRB1*04 as predisposing factor in papillary thyroid carcinoma in Iranian population. This confirms the previous findings for associations between HLA-DRB1 and differentiated carcinomas in other populations