Reproductive Health Screening in Women with Autoimmune Diseases.

Although the female predominance of autoimmune diseases is not completely understood, sex hormones are thought to play a role. Attention to lifelong reproductive health is especially important for women with autoimmune disorders. Many of these women require long-term immunosuppressive therapy that may affect their ability to clear infections, including viruses, and may alter natural tumor surveillance mechanisms.

The Development of Translational Biomarkers as a Tool for Improving the Understanding, Diagnosis and Treatment of Chronic Neuropathic Pain.

Chronic neuropathic pain (CNP) is one of the most significant unmet clinical needs in modern medicine. Alongside the lack of effective treatments, there is a great deficit in the availability of objective diagnostic methods to reliably facilitate an accurate diagnosis. We therefore aimed to determine the feasibility of a simple diagnostic test by analysing differentially expressed genes in the blood of patients diagnosed with CNP of the lower back and compared to healthy human controls.

Use it or lose it: citations predict the continued online availability of published bioinformatics resources.

Scientific Data Analysis Resources (SDARs) such as bioinformatics programs, web servers and databases are integral to modern science, but previous studies have shown that the Uniform Resource Locators (URLs) linking to them decay in a time-dependent manner, with ∼27% decayed to date. Because SDARs are overrepresented among science's most cited papers over the past 20 years, loss of widely used SDARs could be particularly disruptive to scientific research. We identified URLs in MEDLINE abstracts and used crowdsourcing to identify which reported the creation of SDARs.

Loss of CD73 prevents accumulation of alternatively activated macrophages and the formation of prefibrotic macrophage clusters in irradiated lungs.

While radiotherapy is a mainstay for cancer therapy, pneumonitis and fibrosis constitute dose-limiting side effects of thorax and whole body irradiation. So far, the contribution of immune cells to disease progression is largely unknown. Here we studied the role of ecto-5'-nucelotidase (CD73)/adenosine-induced changes in the myeloid compartment in radiation-induced lung fibrosis.

Polygenic risk assessment reveals pleiotropy between sarcoidosis and inflammatory disorders in the context of genetic ancestry.

Sarcoidosis is a complex disease of unknown etiology characterized by the presence of granulomatous inflammation. Though various immune system pathways have been implicated in disease, the relationship between the genetic determinants of sarcoidosis and other inflammatory disorders has not been characterized. Herein, we examined the degree of genetic pleiotropy common to sarcoidosis and other inflammatory disorders to identify shared pathways and disease systems pertinent to sarcoidosis onset.

Downregulation of E Protein Activity Augments an ILC2 Differentiation Program in the Thymus.

Innate lymphoid cells (ILCs) are important regulators in various immune responses. The current paradigm states that all newly made ILCs originate from common lymphoid progenitors in the bone marrow. Id2, an inhibitor of E protein transcription factors, is indispensable for ILC differentiation.

Association of IFIH1 and pro-inflammatory mediators: Potential new clues in SLE-associated pathogenesis.

Antiviral defenses are inappropriately activated in systemic lupus erythematosus (SLE) and association between SLE and the antiviral helicase gene, IFIH1, is well established. We sought to extend the previously reported association of pathogenic soluble mediators and autoantibodies with mouse Mda5 to its human ortholog, IFIH1. To better understand the role this gene plays in human lupus, we assessed association of IFIH1 variants with soluble mediators and autoantibodies in 357 European-American SLE patients, first-degree relatives, and unrelated, unaffected healthy controls.

Anti-La positive, anti-Ro negative subset of primary Sjögren's syndrome: anti-La is a reality but is the disease?

Objectives: To characterise the serological and clinical findings in primary Sjögren's syndrome in which anti-La was found without anti-Ro. We hypothesised that a significant portion of these are falsely negative for anti-Ro60.

Methods: Twenty-nine sera from primary Sjögren's syndrome patients were tested for antibodies directed against La and Ro.

Validating Antibody Specificities for Immunohistochemistry by Protein Blotting Methods.

Immunoblotting has been used in conjunction with other important antibody based detection methods like enzyme linked immunosorbent assay and immunohistochemistry to provide confirmation of results both in research and diagnostic testing. Specificity of antibodies employed for immunohistochemical studies is of critical importance and therefore the use of western blotting is imperative to address specificity of antibodies. In spite of its overall simplicity, western blotting or protein blotting is a powerful procedure for immunodetection of proteins, especially those that are of low abundance, following electrophoretic separation.

Effect of Tobacco Smoking on The Clinical, Histopathological, and Serological Manifestations of Sjögren's Syndrome.

Objectives: To assess the association of smoking habits with the clinical, serological, and histopathological manifestations of Sjögren's syndrome (SS) and non-Sjögren's sicca (non-SS sicca).

Methods: Cross-sectional case-control study of 1288 patients with sicca symptoms (587 SS and 701 non-SS sicca) evaluated in a multi-disciplinary research clinic. Smoking patterns were obtained from questionnaire data and disease-related clinical and laboratory data were compared between current, past, ever, and never smokers.

Pathways of impending disease flare in African-American systemic lupus erythematosus patients.

Immune dysregulation in systemic lupus erythematosus (SLE) contributes to increased disease activity. African-American (AA) SLE patients have an increased prevalence of complications from disease flares and end-organ damage that leads to increased morbidity and early mortality. We previously reported alterations in inflammatory and regulatory immune mediator levels prior to disease flare in European American (EA) SLE patients.

A missense variant in NCF1 is associated with susceptibility to multiple autoimmune diseases.

Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with a strong genetic component characterized by autoantibody production and a type I interferon signature. Here we report a missense variant (g.74779296G>A; p.

Evaluation of 10 SLE susceptibility loci in Asian populations, which were initially identified in European populations.

Ten novel loci have been found to be associated with systemic lupus erythematosus (SLE) susceptibility by a recent genome-wide association study conducted in Europeans. To test their disease associations and genetic similarities/differences in Asians and Europeans, we genotyped the 10 novel single nucleotide polymorphisms (SNPs) and performed an association study. A Chinese cohort from Northern China was recruited as the discovery population, and three East Asian cohorts were included for independent replication.

Confirmation of five novel susceptibility loci for systemic lupus erythematosus (SLE) and integrated network analysis of 82 SLE susceptibility loci.

We recently identified ten novel SLE susceptibility loci in Asians and uncovered several additional suggestive loci requiring further validation. This study aimed to replicate five of these suggestive loci in a Han Chinese cohort from Hong Kong, followed by meta-analysis (11,656 cases and 23,968 controls) on previously reported Asian and European populations, and to perform bioinformatic analyses on all 82 reported SLE loci to identify shared regulatory signatures. We performed a battery of analyses for these five loci, as well as joint analyses on all 82 SLE loci.

Loss of Nrf2 exacerbates the visual deficits and optic neuritis elicited by experimental autoimmune encephalomyelitis.

Purpose: Optic neuritis, inflammation of the optic nerve, is experienced by most patients with multiple sclerosis (MS) and is typically characterized by episodes of acute, monocular vision loss. These episodes of inflammation can lead to damage or degeneration of the retinal ganglion cells (RGCs), the axons of which comprise the optic nerve. Experimental autoimmune encephalomyelitis (EAE) is a well-established model of MS in which mice are immunized to produce a neuroautoimmunity that recapitulates the cardinal hallmarks of human disease, namely, inflammation, demyelination, and neurodegeneration of the brain, spinal cord, and optic nerve.

Transcriptional Classification and Functional Characterization of Human Airway Macrophage and Dendritic Cell Subsets.

The respiratory system is a complex network of many cell types, including subsets of macrophages and dendritic cells that work together to maintain steady-state respiration. Owing to limitations in acquiring cells from healthy human lung, these subsets remain poorly characterized transcriptionally and phenotypically. We set out to systematically identify these subsets in human airways by developing a schema of isolating large numbers of cells by whole-lung bronchoalveolar lavage.

Systemic lupus erythematosus biomarkers: the challenging quest.

SLE, a multisystem heterogeneous disease, is characterized by production of antibodies to cellular components, with activation of both the innate and the adaptive immune system. Decades of investigation of blood biomarkers has resulted in incremental improvements in the understanding of SLE. Owing to the heterogeneity of immune dysregulation, no single biomarker has emerged as a surrogate for disease activity or prediction of disease.

Influence of geolocation and ethnicity on the phenotypic expression of primary Sjögren's syndrome at diagnosis in 8310 patients: a cross-sectional study from the Big Data Sjögren Project Consortium.

Objectives: To analyse the influence of geolocation and ethnicity on the clinical presentation of primary Sjögren's syndrome (SjS) at diagnosis.

Methods: The Big Data Sjögren Project Consortium is an international, multicentre registry designed in 2014. By January 2016, 20 centres from five continents were participating.

Incidence and Prevention of Herpes Zoster Reactivation in Patients with Autoimmune Diseases.

Herpes zoster is the reactivation of latent varicella zoster virus usually occurring decades after initial exposure, and manifesting as a painful vesicular rash occurring along one or more dermatomes. Zoster incidence increases with age as cell mediated immunity against latent virus wanes. Epidemiological evidence suggests that individuals with underlying rheumatic diseases are at increased risk for zoster.

Anti-Ro and Concomitant Anti-La Autoantibodies Strongly Associated With Anti-oxLDL or Anti-Phospholipid Antibody in Systemic Lupus Erythematosus.

Background: Premature atherosclerosis is observed in systemic lupus erythematosus (SLE). Oxidative modification of LDL is associated with atherosclerotic plaque formation.

Objectives: We hypothesized that anti-oxidized LDL (oxLDL) and anti-phospholipid (APL) in SLE sera would segregate with specific antibody subsets, and that anti-oxLDL antibodies will linger in circulation over an extended period.

Genotype-Phenotype Study of the Middle Gangetic Plain in India Shows Association of rs2470102 with Skin Pigmentation.

Our understanding of the genetics of skin pigmentation has been largely skewed towards populations of European ancestry, imparting less attention to South Asian populations, who behold huge pigmentation diversity. Here, we investigate skin pigmentation variation in a cohort of 1,167 individuals in the Middle Gangetic Plain of the Indian subcontinent. Our data confirm the association of rs1426654 with skin pigmentation among South Asians, consistent with previous studies, and also show association for rs2470102 single nucleotide polymorphism.

Effects of transgenic methionine sulfoxide reductase A (MsrA) expression on lifespan and age-dependent changes in metabolic function in mice.

Mechanisms that preserve and maintain the cellular proteome are associated with long life and healthy aging. Oxidative damage is a significant contributor to perturbation of proteostasis and is dealt with by the cell through regulation of antioxidants, protein degradation, and repair of oxidized amino acids. Methionine sulfoxide reductase A (MsrA) repairs oxidation of free- and protein-bound methionine residues through enzymatic reduction and is found in both the cytosol and the mitochondria.

Novel identified associations of RGS1 and RASGRP1 variants in IgA Nephropathy.

Known susceptibility loci together can only explain about 6-8% of the disease heritability of IgA nephropathy (IgAN), suggesting that there are still a large number of genetic variants remained to be discovered. We previously identified IgAN and systemic lupus erythematosus (SLE)/lupus nephritis (LN) shared many loci based on GWAS on Chinese populations. The more recent study with high-density genotyping of immune-related loci in individuals with Asian ancestry identified 10 new and 6 suggestive loci in SLE.

Urinary high-mobility group box-1 associates specifically with lupus nephritis class V.

Introduction: High-mobility group box 1 protein (HMGB-1) has been implicated in the pathogenesis of lupus nephritis (LN). There is increased HMGB-1 expression in the kidneys and increased levels are observed in serum and urine of patients with LN. This study was performed to determine whether the increased urinary HMGB-1 was specific for active lupus or secondary to renal damage.