Mycophenolate mofetil withdrawal in patients with systemic lupus erythematosus: a multicentre, open-label, randomised controlled trial.

Background: Mycophenolate mofetil is an immunosuppressant commonly used to treat systemic lupus erythematosus (SLE) and lupus nephritis. It is a known teratogen associated with significant toxicities, including an increased risk of infections and malignancies. Mycophenolate mofetil withdrawal is desirable once disease quiescence is reached, but the timing of when to do so and whether it provides a benefit has not been well-studied.

B Cell-Directed Therapy in Autoimmunity.

Autoimmune diseases with B cell-directed therapeutics approved by the US Food and Drug Administration are surprisingly diverse in clinical manifestations and pathophysiology. In this review, we focus on recent clinical and mechanistic insights into the efficacy of B cell depletion in these diverse autoimmune disorders, the rapidly expanding armamentarium of approved agents, and future approaches. The pathogenic roles for B cells include direct functions such as production of autoantibodies and proinflammatory cytokines and indirect functions via antigen presentation to T cells.

Immune dysregulation.

The understanding of immune dysregulation in many different diseases continues to grow. There is increasing evidence that altered microbiome and gut barrier dysfunction contribute to systemic inflammation in patients with primary immunodeficiency and in patients with rheumatic disease. Recent research provides insight into the process of induction and maturation of pathogenic age-associated B cells and highlights the role of age-associated B cells in creating tissue inflammation.

Risk and protective factors for heavy episodic drinking among college students: Influence of mental health service use.

This study was designed to assess the relationship between mental health service utilization and heavy episodic drinking (HED) after controlling for demographic and student-level variables. A national sample of college undergraduate respondents to the 2017-2018 Healthy Minds Study survey ( = 67,427). Hierarchical logistic regression entering all variables on a single step.

Biomarkers of Development of Immunity and Allergic Diseases in Farming and Non-farming Lifestyle Infants: Design, Methods and 1 Year Outcomes in the "Zooming in to Old Order Mennonites" Birth Cohort Study.

Traditional farming lifestyle has been shown to be protective against asthma and allergic diseases. The individual factors that appear to be associated with this "farm-life effect" include consumption of unpasteurized farm milk and exposure to farm animals and stables. However, the biomarkers of the protective immunity and those associated with early development of allergic diseases in infancy remain unclear.

Quantitative glycoproteomics of human milk and association with atopic disease.

The prevalence of allergic diseases and asthma is increasing rapidly worldwide, with environmental and lifestyle behaviors implicated as a reason. Epidemiological studies have shown that children who grow up on farms are at lower risk of developing childhood atopic disease, indicating the presence of a protective "farm effect". The Old Order Mennonite (OOM) community in Upstate New York have traditional, agrarian lifestyles, a low rate of atopic disease, and long periods of exclusive breastfeeding.

Traditional Farming Lifestyle in Old Older Mennonites Modulates Human Milk Composition.

Background: In addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown.

Objective: This study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy.

Methods: HM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA and IgA antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites.

B Cell Activation and Plasma Cell Differentiation Are Promoted by IFN-λ in Systemic Lupus Erythematosus.

Type I IFN is essential for viral clearance but also contributes to the pathogenesis of autoimmune diseases, such as systemic lupus erythematosus (SLE), via aberrant nucleic acid-sensing pathways, leading to autoantibody production. Type III IFN (IFN-λ) is now appreciated to have a nonredundant role in viral infection, but few studies have addressed the effects of IFN-λ on immune cells given the more restricted expression of its receptor primarily to the epithelium. In this study, we demonstrate that B cells display a prominent IFN gene expression profile in patients with lupus.

Steroid Allergy in a Patient With Behçet's Disease.

Immediate hypersensitivity reactions to systemic steroids are reported rarely in the literature. The authors present a case of Behçet's disease-associated panuveitis in a patient with skin test confirmed immunoglobulin E-mediated allergy to methylprednisolone and reported allergic reaction to prednisone. The patient tolerated prednisolone eyedrops for his anterior segment disease, as well as oral prednisolone for systemic therapy.

Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle.

Background: Growing up on traditional, single-family farms is associated with protection against asthma in school age, but the mechanisms against early manifestations of atopic disease are largely unknown. We sought determine the gut microbiome and metabolome composition in rural Old Order Mennonite (OOM) infants at low risk and Rochester, NY urban/suburban infants at high risk for atopic diseases.

Methods: In a cohort of 65 OOM and 39 Rochester mother-infant pairs, 101 infant stool and 61 human milk samples were assessed by 16S rRNA gene sequencing for microbiome composition and qPCR to quantify Bifidobacterium spp.

Transmission Electron Microscopy and Electron Energy-Loss Spectroscopy Studies of Hole-Selective Molybdenum Oxide Contacts in Silicon Solar Cells.

In this study, substochiometric hole-selective molybdenum oxide (MoO) contacts in crystalline silicon (c-Si) solar cells were investigated by a combination of transmission electron microscopy (TEM) and spatially resolved electron energy-loss spectroscopy (SR-EELS). It was observed that ≈ 4 nm SiO interlayer grows at the MoO/c-Si interface during the evaporation of MoO over a c-Si substrate. SR-EELS analyses revealed the presence of a 1.

Correction to: Cell Senescence in Lupus.

The original version of this article unfortunately contained mistakes.

Cell Senescence in Lupus.

Purpose Of Review: The concept of cellular senescence has been evolving. Although originally proposed based on studies of serum-driven replication of cell lines in vitro, it is now clear that cellular senescence occurs in vivo. It has also become clear that cellular senescence can be triggered by a number of stimuli such as radiation, chemotherapy, activation of oncogenes, metabolic derangements, and chronic inflammation.

Bone Marrow-Derived Mesenchymal Stem Cells From Patients With Systemic Lupus Erythematosus Have a Senescence-Associated Secretory Phenotype Mediated by a Mitochondrial Antiviral Signaling Protein-Interferon-β Feedback Loop.

Objective: Bone marrow-derived mesenchymal stem cells (BM-MSCs) create a special microenvironment for hematopoiesis and immunity and display robust immunomodulatory properties that are impaired in systemic lupus erythematosus (SLE). This study was undertaken to identify the mechanisms of defects in human SLE BM-MSCs.

Methods: Patients fulfilling SLE classification criteria and healthy controls (n = 6 per group) were recruited according to an institutional review board-approved protocol.

Alcohol-Related Blackouts, Negative Alcohol-Related Consequences, and Motivations for Drinking Reported by Newly Matriculating Transgender College Students.

Background: Many transgender college students struggle with identity formation and other emotional, social, and developmental challenges associated with emerging adulthood. A potential maladaptive coping strategy employed by such students is heavy drinking. Prior literature has suggested greater consumption and negative alcohol-related consequences (ARCs) in transgender students compared with their cisgender peers, but little is known about their differing experiences with alcohol-related blackouts (ARBs).

Alcohol expectancies and drinking behaviors among college students with disordered eating.

Objective: The authors investigated binge drinking, alcohol expectancies, and risky and protective drinking behaviors in relation to disordered eating behaviors in male and female college students.

Participants: The full sample consisted of 7,720 undergraduate students, 18 to 22 years of age. Drinking behaviors were analyzed in 4,592 recent drinkers.

Treatment of systemic lupus erythematosus patients with the BAFF antagonist "peptibody" blisibimod (AMG 623/A-623): results from randomized, double-blind phase 1a and phase 1b trials.

Introduction: Blisibimod is a potent B cell-activating factor (BAFF) antagonist that binds to both cell membrane-expressed and soluble BAFF. The goal of these first-in-human studies was to characterize the safety, tolerability, and pharmacokinetic and pharmacodynamic profiles of blisibimod in subjects with systemic lupus erythematosus (SLE).

Methods: SLE subjects with mild disease that was stable/inactive at baseline received either a single dose of blisibimod (0.

Expansion of Activated Peripheral Blood Memory B Cells in Rheumatoid Arthritis, Impact of B Cell Depletion Therapy, and Biomarkers of Response.

Although B cell depletion therapy (BCDT) is effective in a subset of rheumatoid arthritis (RA) patients, both mechanisms and biomarkers of response are poorly defined. Here we characterized abnormalities in B cell populations in RA and the impact of BCDT in order to elucidate B cell roles in the disease and response biomarkers. In active RA patients both CD27+IgD- switched memory (SM) and CD27-IgD- double negative memory (DN) peripheral blood B cells contained significantly higher fractions of CD95+ and CD21- activated cells compared to healthy controls.

Efficacy and safety of rituximab in patients with active proliferative lupus nephritis: the Lupus Nephritis Assessment with Rituximab study.

Objective: To evaluate the efficacy and safety of rituximab in a randomized, double-blind, placebo-controlled phase III trial in patients with lupus nephritis treated concomitantly with mycophenolate mofetil (MMF) and corticosteroids.

Methods: Patients (n = 144) with class III or class IV lupus nephritis were randomized 1:1 to receive rituximab (1,000 mg) or placebo on days 1, 15, 168, and 182. The primary end point was renal response status at week 52.

Decreased influenza-specific B cell responses in rheumatoid arthritis patients treated with anti-tumor necrosis factor.

Introduction: As a group, rheumatoid arthritis (RA) patients exhibit increased risk of infection, and those treated with anti-tumor necrosis factor (TNF) therapy are at further risk. This increased susceptibility may result from a compromised humoral immune response. Therefore, we asked if short-term effector (d5-d10) and memory (1 month or later) B cell responses to antigen were compromised in RA patients treated with anti-TNF therapy.

Beneficial effect of novel proteasome inhibitors in murine lupus via dual inhibition of type I interferon and autoantibody-secreting cells.

Objective: To investigate the hypothesis that proteasome inhibition may have potential in the treatment of SLE, by targeting plasmacytoid dendritic cells (PDCs) and plasma cells, both of which are critical in disease pathogenesis.

Methods: Lupus-prone mice were treated with the nonselective proteasome inhibitors carfilzomib and bortezomib, the immunoproteasome inhibitor ONX 0914, or vehicle control. Tissue was harvested and analyzed by flow cytometry using standard markers.

Human basophils express amphiregulin in response to T cell-derived IL-3.

Background: Amphiregulin, a member of the epidermal growth factor family, is expressed by activated mouse T(H)2 cells. Amphiregulin produced by mouse hematopoietic cells contributes to the elimination of a nematode infection by a type 2 effector response.

Objective: To identify the human peripheral blood cell population expressing amphiregulin.