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The current data on rates and geographic distribution of vasculitis mortality are limited. We aimed to estimate the mortality rates of primary systemic vasculitis and its geographic distribution using recent population data in the United States. The mortality rates of vasculitis from 1999 to 2019 were obtained from the Center for Disease Control (CDC) Wonder Multiple Cause of Death (MCD). The age-adjusted rates per million for vasculitis as MCD and as an underlying cause of death (UCD) were calculated by state using demographics. A joinpoint regression analysis was applied to evaluate trends over time. The age-adjusted mortality rate of vasculitis as MCD was 4.077 (95% CI: 4.029–4.125) and as a UCD was 1.888 per million (95% CI: 1.855–1.921). Since 1999, mortality rates have progressively decreased. The age-adjusted mortality rate was higher in females than in males. The highest mortality rate for vasculitis as MCD was in White patients (4.371, 95% CI: 4.317–4.424). The northern states and areas with lower populations had higher mortality rates. We found a trend of progressive decreases in the mortality rates of vasculitis, as well as gender, racial, and geographic disparities. Further analyses are warranted to better understand the factors associated with these disparities in order to implement targeted public health interventions to decrease them.

Summary Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by loss of tolerance to nucleic acids and highly diverse clinical manifestations. To assess its molecular heterogeneity, we longitudinally profiled the blood transcriptome of 158 pediatric patients. Using mixed models accounting for repeated measurements, demographics, treatment, disease activity (DA), and nephritis class, we confirmed a prevalent IFN signature and identified a plasmablast signature as the most robust biomarker of DA. We detected gradual enrichment of neutrophil transcripts during progression to active nephritis and distinct signatures in response to treatment in different nephritis subclasses. Importantly, personalized immunomonitoring uncovered individual correlates of disease activity that enabled patient stratification into seven groups, supported by patient genotypes. Our study uncovers the molecular heterogeneity of SLE and provides an explanation for the failure of clinical trials. This approach may improve trial design and implementation of tailored therapies in genetically and clinically complex autoimmune diseases. PaperClip

Background Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. Hence, harnessing the biology of tissue-resident dendritic cells is fundamental for the rational design of vaccines against pathogens. Methods Herein, we characterized the transcriptomes of four antigen-presenting cell subsets from the human vagina (Langerhans cells, CD14- and CD14+ dendritic cells, macrophages) by microarray, at both the transcript and network level, and compared them to those of three skin dendritic cell subsets and blood myeloid dendritic cells. Results We found that genomic fingerprints of antigen-presenting cells are significantly influenced by the tissue of origin as well as by individual subsets. Nonetheless, CD14+ populations from both vagina and skin are geared towards innate immunity and pro-inflammatory responses, whereas CD14- populations, particularly skin and vaginal Langerhans cells, and vaginal CD14- dendritic cells, display both Th2-inducing and regulatory phenotypes. We also identified new phenotypic and functional biomarkers of vaginal antigen-presenting cell subsets. Conclusions We provide a transcriptional database of 87 microarray samples spanning eight antigen-presenting cell populations in the human vagina, skin and blood. Altogether, these data provide molecular information that will further help characterize human tissue antigen-presenting cell lineages and their functions. Data from this study can guide the design of mucosal vaccines against sexually transmitted pathogens. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0098-y) contains supplementary material, which is available to authorized users.

Background: Compelling arguments exist for a role of infectious agent in giant cell arteritis (GCA). Parvovirus B19 and several herpesviruses have focussed the attention in recent years, but the few studies to date have yielded inconsistent results. Objectives: To study the relationship between the presence of parvovirus B19 DNA or major known herpesviruses and the histopathological features of GCA. Study design: Between January 1997 and March 2002, 147 consecutive temporal artery biopsies were performed in our center because of a clinical suspicion of GCA. Using polymerase chain reaction (PCR) procedures validated by the World Health Organization and employed routinely by our laboratory, we examined the paraffin-embedded specimens for DNA from parvovirus B19, herpes simplex viruses (HSV) 1 and 2, Epstein–Barr virus (EBV), varicella-zoster virus (VZV), human cytomegalovirus (HCMV), and human herpesvirus 6 (HHV-6). We investigated positive results further with immunohistochemistry studies. Results: Fifty of the 147 temporal artery biopsies (34%) showed histological features of GCA. Three biopsies (2.5%) were initially PCR positive for parvovirus B19. None of the herpesvirus PCR assays were positive. Upon repeat testing by both PCR and immunohistochemistry, none of the three initially positive parvovirus B19 assays were confirmed. The results of both positive and negative control assays in these studies validated these findings. We confirmed the presence of amplifiable DNA in the temporal artery biopsy specimens using PCR primers for beta-globin and indoleamine 2,3-dioxygenase (IDO). Conclusions: The results of our study do not support a role in the etiopathogenesis of GCA for either parvovirus B19 or any of these six herpesviruses.

Blood monocytes from children with systemic lupus erythematosus (SLE) behave similar to dendritic cells (DCs), and SLE serum induces healthy monocytes to differentiate into DCs in a type I IFN–dependent manner. In this study, we found that these monocytes display significant transcriptional changes, including a prominent IFN signature, compared with healthy controls. Few of those changes, however, explain DC function. Exposure to allogeneic T cells in vitro reprograms SLE monocytes to acquire DC phenotype and function, and this correlates with both IFN-inducible (IP10) and proinflammatory cytokine (IL-1β and IL6) expression. Furthermore, we found that both IFN and SLE serum induce the upregulation of CCR7 transcription in these cells. CCR7 protein expression, however, requires a second signal provided by TLR agonists such as LPS. Thus, SLE serum “primes” a subset of monocytes to readily (

Rationale: Globally there are approximately 9 million new active tuberculosis cases and 1.4 million deaths annually. Effective antituberculosis treatment monitoring is difficult as there are no existing biomarkers of poor adherence or inadequate treatment earlier than 2 months after treatment initiation. Inadequate treatment leads to worsening disease, disease transmission and drug resistance. Objectives: To determine if blood transcriptional signatures change in response to antituberculosis treatment and could act as early biomarkers of a successful response. Methods: Blood transcriptional profiles of untreated active tuberculosis patients in South Africa were analysed before, during (2 weeks and 2 months), at the end of (6 months) and after (12 months) antituberculosis treatment, and compared to individuals with latent tuberculosis. An active-tuberculosis transcriptional signature and a specific treatment-response transcriptional signature were derived. The specific treatment response transcriptional signature was tested in two independent cohorts. Two quantitative scoring algorithms were applied to measure the changes in the transcriptional response. The most significantly represented pathways were determined using Ingenuity Pathway Analysis. Results: An active tuberculosis 664-transcript signature and a treatment specific 320-transcript signature significantly diminished after 2 weeks of treatment in all cohorts, and continued to diminish until 6 months. The transcriptional response to treatment could be individually measured in each patient. Conclusions: Significant changes in the transcriptional signatures measured by blood tests were readily detectable just 2 weeks after treatment initiation. These findings suggest that blood transcriptional signatures could be used as early surrogate biomarkers of successful treatment response.

Staphylococcus aureus infections are associated with diverse clinical manifestations leading to significant morbidity and mortality. To define the role of the host response in the clinical manifestations of the disease, we characterized whole blood transcriptional profiles of children hospitalized with community-acquired S. aureus infection and phenotyped the bacterial strains isolated. The overall transcriptional response to S. aureus infection was characterized by over-expression of innate immunity and hematopoiesis related genes and under-expression of genes related to adaptive immunity. We assessed individual profiles using modular fingerprints combined with the molecular distance to health (MDTH), a numerical score of transcriptional perturbation as compared to healthy controls. We observed significant heterogeneity in the host signatures and MDTH, as they were influenced by the type of clinical presentation, the extent of bacterial dissemination, and time of blood sampling in the course of the infection, but not by the bacterial isolate. System analysis approaches provide a new understanding of disease pathogenesis and the relation/interaction between host response and clinical disease manifestations.

Objective:To date, it has not been adequately proven whether the published formulas used to obtain incidence from the prevalence of nosocomial infections provide a good estimate of real incidence. With the hypothesis that within the hospital setting prevalence may be lower than incidence, the aim of this study was to analyze the behavior of point prevalence as it relates to cumulative incidence and duration of infection.Design:Hospital simulation study.Methods:By randomly selecting a sample of infected patients within a specific range of cumulative incidences and infection durations, we constructed a simulated hospital population, allowing us to estimate daily point prevalences and their maximum and minimum values. The association between the different components of stay and cumulative incidence was evaluated to obtain a more accurate estimate of incidence.Results:Prevalence can be lower than, equal to, or higher than the corresponding incidence. For all incidence levels, prevalence was increasing with duration. Between 14 and 20 days of infection duration, prevalence was consistently lower than incidence. Prevalence duration of infection was approximately half the time of the total duration.Conclusions:The existing formulas relating incidence and prevalence can frequently be inadequate. Until a validated system for converting prevalence into incidence is available, we do not believe their use is appropriate.