Tracking of Systemic Lupus Erythematosus (SLE) Longitudinally Using Biosensor and Patient-Reported Data: A Report on the Fully Decentralized Mobile Study to Measure and Predict Lupus Disease Activity Using Digital Signals-The OASIS Study.

(1) Objective: Systemic lupus erythematosus (SLE) is a complex disease involving immune dysregulation, episodic flares, and poor quality of life (QOL). For a decentralized digital study of SLE patients, machine learning was used to assess patient-reported outcomes (PROs), QOL, and biometric data for predicting possible disease flares. (2) Methods: Participants were recruited from the LupusCorner online community.

Gram-Positive Bacteria Cell Wall Peptidoglycan Polymers Activate Human Dendritic Cells to Produce IL-23 and IL-1β and Promote T17 Cell Differentiation.

Gram-positive bacterial infections are a major cause of organ failure and mortality in sepsis. Cell wall peptidoglycan (PGN) is shed during bacterial replication, and PGN promotes a sepsis-like pathology in baboons. Herein, we determined the ability of polymeric PGN free from TLR ligands to shape human dendritic cell (DC) responses that are important for the initiation of T cell immunity.

A Flare Risk Index Informed by Select Immune Mediators in Systemic Lupus Erythematosus.

Objective: Systemic lupus erythematosus (SLE) is marked by immune dysregulation linked to varied clinical disease activity. Using a unique longitudinal cohort of SLE patients, this study sought to identify optimal immune mediators informing an empirically refined flare risk index (FRI) reflecting altered immunity prior to clinical disease flare.

Methods: Thirty-seven SLE-associated plasma mediators were evaluated by microfluidic immunoassay in 46 samples obtained in SLE patients with an imminent clinical disease flare (preflare) and 53 samples obtained in SLE patients without a flare over a corresponding period (pre-nonflare).

Pre-Clinical Autoimmunity in Lupus Relatives: Self-Reported Questionnaires and Immune Dysregulation Distinguish Relatives Who Develop Incomplete or Classified Lupus From Clinically Unaffected Relatives and Unaffected, Unrelated Individuals.

Systemic lupus erythematosus (SLE) is propelled by pathogenic autoantibody (AutoAb) and immune pathway dysregulation. Identifying populations at risk of reaching classified SLE is essential to curtail inflammatory damage. Lupus blood relatives (Rel) have an increased risk of developing SLE.

Clinical disease activity and flare in SLE: Current concepts and novel biomarkers.

Systemic lupus erythematosus (SLE) is a complex and heterogeneous systemic autoimmune disease associated with innate and adaptive immune dysregulation. SLE occurs primarily in females of childbearing age, with increased prevalence and severity in minority populations. Despite improvements in treatment modalities, SLE patients frequently experience periods of heightened disease activity and flare that can lead to permanent organ damage, increased morbidity, and early mortality.

Epstein-Barr Functional Mimicry: Pathogenicity of Oncogenic Latent Membrane Protein-1 in Systemic Lupus Erythematosus and Autoimmunity.

Systemic lupus erythematosus (SLE) and other autoimmune diseases are propelled by immune dysregulation and pathogenic, disease-specific autoantibodies. Autoimmunity against the lupus autoantigen Sm is associated with cross-reactivity to Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1). Additionally, EBV latent membrane protein-1 (LMP1), initially noted for its oncogenic activity, is an aberrantly active functional mimic of the B cell co-stimulatory molecule CD40.

Associations Between Smoking and Systemic Lupus Erythematosus-Related Cytokines and Chemokines Among US Female Nurses.

Objective: Smoking has been associated with increased systemic lupus erythematosus (SLE) risk, but the biologic basis for this association is unknown. Our objective was to investigate whether women's smoking was positively associated with SLE-associated proinflammatory chemokines/cytokines (stem cell factor [SCF], B lymphocyte stimulator [BLyS], interferon-γ-inducible 10-kd protein [IP-10], and interferon-α); or negatively associated with antiinflammatory cytokine interleukin-10 (IL-10); and whether associations were modified by SLE-related autoantibody status.

Methods: The Nurses' Health Study (NHS, n = 121,700) and NHSII (n = 116,429) cohorts were begun in 1976 and 1989.

Associations between daily alcohol consumption and systemic lupus erythematosus-related cytokines and chemokines among US female nurses without SLE.

Objectives: Moderate alcohol consumption has been associated with decreased systemic lupus erythematosus risk, but the biologic basis for this association is unknown. We aimed to determine whether moderate alcohol consumption was associated with lower concentrations of systemic lupus erythematosus-associated chemokines/cytokines in an ongoing cohort of female nurses without systemic lupus erythematosus, and whether the association was modified by the presence of systemic lupus erythematosus-related autoantibodies.

Methods: About 25% of participants from the Nurses' Health Study ( = 121,700 women) and Nurses' Health Study 2 ( = 116,429) donated a blood sample; of these, 1177 women were without systemic lupus erythematosus at time of donation.

Autoantibody-positive healthy individuals with lower lupus risk display a unique immune endotype.

Background: Autoimmune diseases comprise a spectrum of illnesses and are on the rise worldwide. Although antinuclear antibodies (ANAs) are detected in many autoimmune diseases, up to 20% of healthy women are ANA-positive (ANA+) and most will never develop clinical symptoms. Furthermore, disease transition is higher among ANA+ African Americans compared with ANA+ European Americans.

Adults with systemic lupus exhibit distinct molecular phenotypes in a cross-sectional study.

Background: The clinical and pathologic diversity of systemic lupus erythematosus (SLE) hinders diagnosis, management, and treatment development. This study addresses heterogeneity in SLE through comprehensive molecular phenotyping and machine learning clustering.

Methods: Adult SLE patients ( = 198) provided plasma, serum, and RNA.

Author Correction: Immunologic findings precede rapid lupus flare after transient steroid therapy.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Unique Sjögren's syndrome patient subsets defined by molecular features.

Objective: To address heterogeneity complicating primary SS (pSS) clinical trials, research and care by characterizing and clustering patients by their molecular phenotypes.

Methods: pSS patients met American-European Consensus Group classification criteria and had at least one systemic manifestation and stimulated salivary flow of ⩾0.1 ml/min.

Immunologic findings precede rapid lupus flare after transient steroid therapy.

Systemic lupus erythematosus (SLE) flares elicit progressive organ damage, leading to disability and early mortality. This study evaluated clinical and immunologic factors associated with impending flare in the Biomarkers of Lupus Disease study. Autoantibodies and 32 soluble mediators were measured by multiplex assays, immune pathway activation by gene expression module scores, and immune cell subset frequencies and activation states by flow cytometry.

Unique clinical characteristics, autoantibodies and medication use in Native American patients with systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease with varied morbidity and mortality. We assessed clinical presentations, autoantibody specificities and therapeutic interventions in Native American (NA) patients with SLE.

Methods: Patients with SLE meeting 1997 American College of Rheumatology classification criteria (n=3148) were enrolled between 1992 and 2010 in the multiethnic, cross-sectional Lupus Family Registry and Repository.

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.

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.

Clinical and Serologic Features in Patients With Incomplete Lupus Classification Versus Systemic Lupus Erythematosus Patients and Controls.

Objective: Incomplete lupus erythematosus (ILE) involves clinical and/or serologic manifestations consistent with but insufficient for systemic lupus erythematosus (SLE) classification. Because the nature of ILE is poorly understood and no treatment recommendations exist, we examined the clinical manifestations, medication history, and immunologic features in a diverse collection of ILE and SLE patients.

Methods: Medical records of subjects enrolled in the Lupus Family Registry and Repository were reviewed for medication history and American College of Rheumatology (ACR) classification criteria to identify ILE patients (3 ACR criteria; n = 440) and SLE patients (≥4 ACR criteria; n = 3,397).

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.

Discerning Risk of Disease Transition in Relatives of Systemic Lupus Erythematosus Patients Utilizing Soluble Mediators and Clinical Features.

Objective: Systemic lupus erythematosus (SLE) and other autoimmune diseases cause significant morbidity. Identifying populations at risk of developing SLE is essential for curtailing irreversible inflammatory damage. The aim of this study was to identify factors associated with transition to classified disease that would inform our understanding of the risk of SLE.

Dysregulation of innate and adaptive serum mediators precedes systemic lupus erythematosus classification and improves prognostic accuracy of autoantibodies.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a poorly understood preclinical stage of immune dysregulation and symptom accrual. Accumulation of antinuclear autoantibody (ANA) specificities is a hallmark of impending clinical disease. Yet, many ANA-positive individuals remain healthy, suggesting that additional immune dysregulation underlies SLE pathogenesis.

Impact of heart rate variability, a marker for cardiac health, on lupus disease activity.

Background: Decreased heart rate variability (HRV) is associated with adverse outcomes in cardiovascular diseases and has been observed in patients with systemic lupus erythematosus (SLE). We examined the relationship of HRV with SLE disease activity and selected cytokine pathways.

Methods: Fifty-three patients from the Oklahoma Lupus Cohort were evaluated at two visits each.

Combined role of vitamin D status and CYP24A1 in the transition to systemic lupus erythematosus.

Objective: We examined whether measures of vitamin D were associated with transitioning to systemic lupus erythematosus (SLE) in individuals at risk for SLE.

Methods: 436 individuals who reported having a relative with SLE but who did not have SLE themselves were evaluated at baseline and again an average of 6.3 (±3.

Unique Inflammatory Mediators and Specific IgE Levels Distinguish Local from Systemic Reactions after Anthrax Vaccine Adsorbed Vaccination.

Although the U.S. National Academy of Sciences concluded that anthrax vaccine adsorbed (AVA) has an adverse event (AE) profile similar to those of other adult vaccines, 30 to 70% of queried AVA vaccinees report AEs.

Altered type II interferon precedes autoantibody accrual and elevated type I interferon activity prior to systemic lupus erythematosus classification.

Objectives: The relationship of immune dysregulation and autoantibody production that may contribute to systemic lupus erythematosus (SLE) pathogenesis is unknown. This study evaluates the individual and combined contributions of autoantibodies, type I interferon (IFN-α) activity, and IFN-associated soluble mediators to disease development leading to SLE.

Methods: Serial serum specimens from 55 individuals collected prior to SLE classification (average timespan=4.