High Interferon Signature Leads to Increased STAT1/3/5 Phosphorylation in PBMCs From SLE Patients by Single Cell Mass Cytometry.

The establishment of an "interferon (IFN) signature" to subset SLE patients on disease severity has led to therapeutics targeting IFNα. Here, we investigate IFN signaling in SLE using multiplexed protein arrays and single cell cytometry by time of flight (CyTOF). First, the IFN signature for SLE patients (n=81) from the Stanford Lupus Registry is determined using fluidigm qPCR measuring 44 previously determined IFN-inducible transcripts.

Implementation of a low titer group O whole blood program for a law enforcement tactical team.

The Texas Ranger Special Operations Group (SOG) performs high-risk warrant service and responds to callouts for evolving kinetic situations and special missions as required. These operations may occur many hours from a trauma center. Fresh whole blood (FWB) transfusions may offer a stopgap for those who are critically injured.

Integrated, multicohort analysis reveals unified signature of systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a complex autoimmune disease that follows an unpredictable disease course and affects multiple organs and tissues. We performed an integrated, multicohort analysis of 7,471 transcriptomic profiles from 40 independent studies to identify robust gene expression changes associated with SLE. We identified a 93-gene signature (SLE MetaSignature) that is differentially expressed in the blood of patients with SLE compared with healthy volunteers; distinguishes SLE from other autoimmune, inflammatory, and infectious diseases; and persists across diverse tissues and cell types.

High-Resolution Analysis of Antibodies to Post-Translational Modifications Using Peptide Nanosensor Microarrays.

Autoantibodies are a hallmark of autoimmune diseases such as lupus and have the potential to be used as biomarkers for diverse diseases, including immunodeficiency, infectious disease, and cancer. More precise detection of antibodies to specific targets is needed to improve diagnosis of such diseases. Here, we report the development of reusable peptide microarrays, based on giant magnetoresistive (GMR) nanosensors optimized for sensitively detecting magnetic nanoparticle labels, for the detection of antibodies with a resolution of a single post-translationally modified amino acid.

Multiplex giant magnetoresistive biosensor microarrays identify interferon-associated autoantibodies in systemic lupus erythematosus.

High titer, class-switched autoantibodies are a hallmark of systemic lupus erythematosus (SLE). Dysregulation of the interferon (IFN) pathway is observed in individuals with active SLE, although the association of specific autoantibodies with chemokine score, a combined measurement of three IFN-regulated chemokines, is not known. To identify autoantibodies associated with chemokine score, we developed giant magnetoresistive (GMR) biosensor microarrays, which allow the parallel measurement of multiple serum antibodies to autoantigens and peptides.

Development of Th17-Associated Interstitial Kidney Inflammation in Lupus-Prone Mice Lacking the Gene Encoding STAT-1.

Objective: Type I interferon (IFN) signaling is a central pathogenic pathway in systemic lupus erythematosus (SLE), and therapeutics targeting type I IFN signaling are in development. Multiple proteins with overlapping functions play a role in IFN signaling, but the signaling events downstream of receptor engagement are unclear. This study was undertaken to investigate the roles of the type I and type II IFN signaling components IFN-α/β/ω receptor 2 (IFNAR-2), IFN regulatory factor 9 (IRF-9), and STAT-1 in a mouse model of SLE.

Mapping epitopes of U1-70K autoantibodies at single-amino acid resolution.

The mechanisms underlying development of ribonucleoprotein (RNP) autoantibodies are unclear. The U1-70K protein is the predominant target of RNP autoantibodies, and the RNA binding domain has been shown to be the immunodominant autoantigenic region of U1-70K, although the specific epitopes are not known. To precisely map U1-70K epitopes, we developed silicon-based peptide microarrays with >5700 features, corresponding to 843 unique peptides derived from the U1-70K protein.

Autoantigen microarrays reveal autoantibodies associated with proliferative nephritis and active disease in pediatric systemic lupus erythematosus.

Introduction: Pediatric systemic lupus erythematosus (pSLE) patients often initially present with more active and severe disease than adults, including a higher frequency of lupus nephritis. Specific autoantibodies, including anti-C1q, anti-DNA and anti-alpha-actinin, have been associated with kidney involvement in SLE, and DNA antibodies are capable of initiating early-stage lupus nephritis in severe combined immunodeficiency (SCID) mice. Over 100 different autoantibodies have been described in SLE patients, highlighting the need for comprehensive autoantibody profiling.

The synergetic effect of ambient PM2.5 exposure and rhinovirus infection in airway dysfunction in asthma: a pilot observational study from the Central Valley of California.

Background: Elevated levels of particulate matter PM2.5 and rhinovirus infection have been known to exacerbate asthma. However, the combined effect of rhinovirus infection and high PM2.