Safety and tolerability of hydroxychloroquine in health care workers and first responders for the prevention of COVID-19: WHIP COVID-19 Study.

Background: Health care workers (HCW) are among the highest risk groups for acquisition of COVID-19 because of occupational exposures. The WHIP COVID-19 Study aimed to evaluate the safety and efficacy of hydroxychloroquine (HCQ) as chemoprophylaxis for SARS-CoV-2 infection in this population.

Methods: HCW, first responders, and other occupationally high-risk participants were enrolled in a randomized, placebo-controlled clinical study of HCQ from April to October 2020.

The role of tocilizumab therapy in critically ill patients with severe acute respiratory syndrome coronavirus 2.

Context: Tocilizumab (TCZ), an interleukin-6 (IL-6) receptor antagonist, has been approved for use in rheumatoid arthritis and cytokine storm syndrome (CSS) associated with chimeric antigen receptor T cells treatment. Although TCZ is currently utilized in the treatment of critically ill coronavirus 2019 (COVID-19) patients, data on survival impact is minimal.

Objectives: To assess the mortality rate of patients presenting with COVID-19 who received TCZ for suspected CSS.

Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus.

Objective: Enrollment of patients of Black African ancestry with systemic lupus erythematosus (SLE) in phase II and phase III of the belimumab trials was not reflective of the racial distribution observed in the lupus population. This study was undertaken to assess the efficacy and safety of intravenous (IV) belimumab plus standard therapy in patients of self-identified Black race.

Methods: EMBRACE (GSK Study BEL115471; ClinicalTrials.

Subclinical CMV viremia is associated with increased nosocomial infections and prolonged hospitalization in patients with systemic autoimmune diseases.

Objective: Subclinical cytomegalovirus (CMV) viremia has been associated with other infections, prolonged hospitalization, and mortality in select immunosuppressed populations. We examined the incidence and outcomes of subclinical CMV viremia in hospitalized patients with systemic autoimmune diseases (AD) [systemic lupus erythematosus (SLE) or anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV)] using a highly sensitive CMV assay.

Methods: Prospectively collected samples were obtained from AD hospitalized patients at study entry with a second sample collected 1 week later or at hospital discharge.

Mortality and adverse events of special interest with intravenous belimumab for adults with active, autoantibody-positive systemic lupus erythematosus (BASE): a multicentre, double-blind, randomised, placebo-controlled, phase 4 trial.

Background: Belimumab is approved for the treatment of active systemic lupus erythematosus (SLE). Although clinical trials showed a favourable benefit-risk profile, numerical differences in the incidence of mortality and adverse events of special interest (AESIs) have been reported. We assessed the frequency of these events in patients with SLE receiving belimumab or placebo plus standard therapy.

A longitudinal and transancestral analysis of DNA methylation patterns and disease activity in lupus patients.

Epigenetic dysregulation is implicated in the pathogenesis of lupus. We performed a longitudinal analysis to assess changes in DNA methylation in lupus neutrophils over 4 years of follow-up and across disease activity levels using 229 patient samples. We demonstrate that DNA methylation profiles in lupus are partly determined by ancestry-associated genetic variations and are highly stable over time.

Derivation of an angiographically based classification system in Takayasu's arteritis: an observational study from India and North America.

Objectives: To develop and replicate, using data-driven methods, a novel classification system in Takayasu's arteritis based on distribution of arterial lesions.

Methods: Patients were included from four international cohorts at major academic centres: India (Christian Medical College Vellore); North America (National Institutes of Health, Vasculitis Clinical Research Consortium and Cleveland Clinic Foundation). All patients underwent whole-body angiography of the aorta and branch vessels, with categorization of arterial damage (stenosis, occlusion or aneurysm) in 13 territories.

Patterns of Arterial Disease in Takayasu Arteritis and Giant Cell Arteritis.

Objective: To identify and validate, using computer-driven methods, patterns of arterial disease in Takayasu arteritis (TAK) and giant cell arteritis (GCA).

Methods: Patients with TAK or GCA were studied from the Diagnostic and Classification Criteria for Vasculitis (DCVAS) cohort and a combined North American cohort. Case inclusion required evidence of large-vessel involvement, defined as stenosis, occlusion, or aneurysm by angiography/ultrasonography, or increased F-fluorodeoxyglucose (FDG) uptake by positron emission tomography (PET) in at least 1 of 11 specified arterial territories.

Role of Macrophage Migration Inhibitory Factor in Granulomatosis With Polyangiitis.

Objective: To examine the association between macrophage migration inhibitory factor (MIF) promoter polymorphisms and granulomatosis with polyangiitis (GPA) in human subjects, and to assess the role of MIF in a murine model of granulomatous vasculitis.

Methods: The human study involved 1,077 patients with GPA and healthy controls whose serum was genotyped by capillary electrophoresis for the MIF -794 CATT promoter microsatellite (rs5844572). MIF promoter, CATT-length-dependent gene expression in response to β-glucan was assessed by gene reporter assays.

Brief Report: Whole-Exome Sequencing to Identify Rare Variants and Gene Networks That Increase Susceptibility to Scleroderma in African Americans.

Objective: Whole-exome sequencing (WES) studies in systemic sclerosis (SSc) patients of European American (EA) ancestry have identified variants in the ATP8B4 gene and enrichment of variants in genes in the extracellular matrix (ECM)-related pathway that increase SSc susceptibility. This study was undertaken to evaluate the association of the ATP8B4 gene and the ECM-related pathway with SSc in a cohort of African American (AA) patients.

Methods: SSc patients of AA ancestry were enrolled from 23 academic centers across the US under the Genome Research in African American Scleroderma Patients consortium.

CD4+CD28+KIR+CD11a T cells correlate with disease activity and are characterized by a pro-inflammatory epigenetic and transcriptional profile in lupus patients.

Objective: The goal of this study was to comprehensively characterize CD4+CD28+ T cells overexpressing CD11a and KIR genes, and examine the relationship between this T cell subset, genetic risk, and disease activity in lupus.

Methods: The size of the CD4+CD28+KIR+CD11a T cell subset was determined by flow cytometry, and total genetic risk for lupus was calculated in 105 female patients using 43 confirmed genetic susceptibility loci. Primary CD4+CD28+KIR+CD11a T cells were isolated from lupus patients or were induced from healthy individuals using 5-azacytidine.

Age-associated DNA methylation changes in naive CD4 T cells suggest an evolving autoimmune epigenotype in aging T cells.

Aim: We sought to define age-associated DNA methylation changes in naive CD4 T cells.

Materials & Methods: Naive CD4 T cells were collected from 74 healthy individuals (age 19-66 years), and age-related DNA methylation changes were characterized.

Results: We identified 11,431 age-associated CpG sites, 57% of which were hypermethylated with age.

Epigenetic Reprogramming in Naive CD4+ T Cells Favoring T Cell Activation and Non-Th1 Effector T Cell Immune Response as an Early Event in Lupus Flares.

Objective: Systemic lupus erythematosus (SLE) is a relapsing autoimmune disease that affects multiple organ systems. T cells play an important role in the pathogenesis of lupus; however, early T cell events triggering disease flares are incompletely understood. This study was undertaken to examine DNA methylation in naive CD4+ T cells from lupus patients to determine if epigenetic remodeling in CD4+ T cells is an early event in lupus flares.

Ethnicity-specific epigenetic variation in naïve CD4+ T cells and the susceptibility to autoimmunity.

Background: Genetic and epigenetic variability contributes to the susceptibility and pathogenesis of autoimmune diseases. T cells play an important role in several autoimmune conditions, including lupus, which is more common and more severe in people of African descent. To investigate inherent epigenetic differences in T cells between ethnicities, we characterized genome-wide DNA methylation patterns in naïve CD4+ T cells in healthy African-Americans and European-Americans, and then confirmed our findings in lupus patients.

Autoimmune disease and vaccination: impact on infectious disease prevention and a look at future applications.

Vaccines hold promise both for the prevention of infections and as potential immunologic therapy for patients with autoimmune disease (AD). These patients are at high risk for both common and opportunistic infections, but this risk can be significantly reduced and even obviated with the use of recommended available vaccines. Unfortunately, patients with ADs are not routinely offered or provided indicated vaccinations and have higher rates of complications from vaccine-preventable illnesses than patients without ADs.

DNA methylation patterns in naïve CD4+ T cells identify epigenetic susceptibility loci for malar rash and discoid rash in systemic lupus erythematosus.

Objective: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterised by heterogeneous clinical manifestations, autoantibody production and epigenetic dysregulation in T cells. We sought to investigate the epigenetic contribution to the development of cutaneous manifestations in SLE.

Methods: We performed genome-wide DNA methylation analyses in patients with SLE stratified by a history of malar rash, discoid rash or neither cutaneous manifestation, and age, sex and ethnicity matched healthy controls.

Renal involvement in lupus is characterized by unique DNA methylation changes in naïve CD4+ T cells.

Systemic lupus erythematosus is a multi-system disease characterized by wide-spread DNA methylation changes. To identify epigenetic susceptibility loci for lupus nephritis, genome-wide DNA methylation changes in naïve CD4+ T cells were compared between two sets of lupus patients with and without a history of renal involvement. A total of 56 lupus patients (28 with renal involvement and 28 without renal involvement), and 56 age-, sex-, and ethnicity-matched healthy controls were included in our study.

Disease Relapses among Patients with Giant Cell Arteritis: A Prospective, Longitudinal Cohort Study.

Objective: To evaluate the frequency, timing, and clinical features of relapses in giant cell arteritis (GCA).

Methods: Patients with GCA enrolled in a prospective, multicenter, longitudinal study were included in the analysis. Relapse was defined as either new disease activity after a period of remission or worsening disease activity.

Identification of Susceptibility Loci in IL6, RPS9/LILRB3, and an Intergenic Locus on Chromosome 21q22 in Takayasu Arteritis in a Genome-Wide Association Study.

Objective: Takayasu arteritis is a rare large vessel vasculitis with incompletely understood etiology. This study was undertaken to perform the first unbiased genome-wide association analysis of Takayasu arteritis.

Methods: Two independent cohorts of patients with Takayasu arteritis from Turkey and North America were included in our study.

Value of commonly measured laboratory tests as biomarkers of disease activity and predictors of relapse in eosinophilic granulomatosis with polyangiitis.

Objective: The aim of this study was to assess the clinical value of absolute eosinophil count, serum IgE, ESR and CRP as longitudinal biomarkers of disease activity and predictors of relapse in eosinophilic granulomatosis with polyangiitis (Churg-Strauss, EGPA).

Methods: Patients were selected from an observational EGPA cohort. Absolute eosinophil count, IgE, ESR and CRP were measured quarterly.

New features of disease after diagnosis in 6 forms of systemic vasculitis.

Objective: To quantify the occurrence of features of vasculitis that initially present after diagnosis in 6 types of primary vasculitis.

Methods: Standardized collection of data on 95 disease manifestations in 6 vasculitides, including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (Churg-Strauss; EGPA), polyarteritis nodosa (PAN), giant cell arteritis (GCA), and Takayasu arteritis (TAK), was obtained within a set of multicenter longitudinal, observational cohorts. For each form of vasculitis, the frequency of disease-specific manifestations at diagnosis was compared to the cumulative frequency of each manifestation.

Identification of multiple genetic susceptibility loci in Takayasu arteritis.

Takayasu arteritis is a rare inflammatory disease of large arteries. The etiology of Takayasu arteritis remains poorly understood, but genetic contribution to the disease pathogenesis is supported by the genetic association with HLA-B*52. We genotyped ~200,000 genetic variants in two ethnically divergent Takayasu arteritis cohorts from Turkey and North America by using a custom-designed genotyping platform (Immunochip).

urinary biomarkers in relapsing antineutrophil cytoplasmic antibody-associated vasculitis.

Objective: Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL).

Methods: Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort.

Distribution of arterial lesions in Takayasu's arteritis and giant cell arteritis.

Objectives: To compare patterns of arteriographic lesions of the aorta and primary branches in patients with Takayasu's arteritis (TAK) and giant cell arteritis (GCA).

Methods: Patients were selected from two North American cohorts of TAK and GCA. The frequency of arteriographic lesions was calculated for 15 large arteries.