Biologic Medications for Severe Asthma: Implications for Understanding Pathogenic Heterogeneity and Endotypes.

Asthma is a chronic inflammatory disease of the airways long known for phenotypic heterogeneity. Phenotyping studies in asthma have led to a better characterization of disease pathogenesis, yet further work is needed to pair available treatments with disease endotypes. In this review, the biology of targeted pathways is discussed along with the efficacy of biologic therapies targeting those pathways.

Transient anti-interferon autoantibodies in the airways are associated with recovery from COVID-19.

Preexisting anti-interferon-α (anti-IFN-α) autoantibodies in blood are associated with susceptibility to life-threatening COVID-19. However, it is unclear whether anti-IFN-α autoantibodies in the airways, the initial site of infection, can also determine disease outcomes. In this study, we developed a multiparameter technology, FlowBEAT, to quantify and profile the isotypes of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and anti-IFN-α antibodies in longitudinal samples collected over 20 months from the airways and blood of 129 donors spanning mild to severe COVID-19.

MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID.

Post-acute sequelae of SARS-CoV-2 (SARS2) infection (PASC) is a heterogeneous condition, but the main viral drivers are unknown. Here, we use MENSA, Media Enriched with Newly Synthesized Antibodies, secreted exclusively from circulating human plasmablasts, to provide an immune snapshot that defines the underlying viral triggers. We provide proof-of-concept testing that the MENSA technology can capture the new host immune response to accurately diagnose acute primary and breakthrough infections when known SARS2 virus or proteins are present.

Patients taking benralizumab, dupilumab, or mepolizumab have lower postvaccination SARS-CoV-2 immunity.

Background: Biologic therapies inhibiting the IL-4 or IL-5 pathways are very effective in the treatment of asthma and other related conditions. However, the cytokines IL-4 and IL-5 also play a role in the generation of adaptive immune responses. Although these biologics do not cause overt immunosuppression, their effect in primary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization has not been studied completely.

Chronic inflammation, neutrophil activity, and autoreactivity splits long COVID.

While immunologic correlates of COVID-19 have been widely reported, their associations with post-acute sequelae of COVID-19 (PASC) remain less clear. Due to the wide array of PASC presentations, understanding if specific disease features associate with discrete immune processes and therapeutic opportunities is important. Here we profile patients in the recovery phase of COVID-19 via proteomics screening and machine learning to find signatures of ongoing antiviral B cell development, immune-mediated fibrosis, and markers of cell death in PASC patients but not in controls with uncomplicated recovery.

Bridging the Gap between Innate and Adaptive Immunity in the Lung: Summary of the Aspen Lung Conference 2022.

Although significant strides have been made in the understanding of pulmonary immunology, much work remains to be done to comprehensively explain coordinated immune responses in the lung. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic only served to highlight the inadequacy of current models of host-pathogen interactions and reinforced the need for current and future generations of immunologists to unravel complex biological questions. As part of that effort, the 64th Annual Thomas L.

Single-cell analysis of human nasal mucosal IgE antibody secreting cells reveals a newly minted phenotype.

Immunoglobulin (Ig) E is central to the pathogenesis of allergic conditions, including allergic fungal rhinosinusitis. However, little is known about IgE antibody secreting cells (ASCs). We performed single-cell RNA sequencing from cluster of differentiation (CD)19 and CD19 ASCs of nasal polyps from patients with allergic fungal rhinosinusitis (n = 3).

CCL5 is a potential bridge between type 1 and type 2 inflammation in asthma.

Background: Type 1 (T1) inflammation (marked by IFN-γ expression) is now consistently identified in subsets of asthma cohorts, but how it contributes to disease remains unclear.

Objective: We sought to understand the role of CCL5 in asthmatic T1 inflammation and how it interacts with both T1 and type 2 (T2) inflammation.

Methods: CCL5, CXCL9, and CXCL10 messenger RNA expression from sputum bulk RNA sequencing, as well as clinical and inflammatory data were obtained from the Severe Asthma Research Program III (SARP III).

Dysregulated naive B cells and de novo autoreactivity in severe COVID-19.

Severe SARS-CoV-2 infection has been associated with highly inflammatory immune activation since the earliest days of the COVID-19 pandemic. More recently, these responses have been associated with the emergence of self-reactive antibodies with pathologic potential, although their origins and resolution have remained unclear. Previously, we and others have identified extrafollicular B cell activation, a pathway associated with the formation of new autoreactive antibodies in chronic autoimmunity, as a dominant feature of severe and critical COVID-19 (refs.

Inactivation of SARS-CoV-2 and COVID-19 Patient Samples for Contemporary Immunology and Metabolomics Studies.

Due to the severity of COVID-19 disease, the U.S. Centers for Disease Control and Prevention and World Health Organization recommend that manipulation of active viral cultures of SARS-CoV-2 and respiratory secretions from COVID-19 patients be performed in biosafety level (BSL)3 laboratories.

Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection.

Within 8 weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrated the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence.

Diagnosis of Streptococcus pneumoniae infection using circulating antibody secreting cells.

Background: Streptococcus pneumoniae infections cause morbidity and mortality worldwide. A rapid, simple diagnostic method could reduce the time needed to introduce definitive therapy potentially improving patient outcomes.

Methods: We introduce two new methods for diagnosing S.

Extrafollicular IgD+ B cells generate IgE antibody secreting cells in the nasal mucosa.

Increased IgE is a typical feature of allergic rhinitis. Local class-switch recombination has been intimated but B cell precursors and mechanisms remain elusive. Here we describe the dynamics underlying the generation of IgE-antibody secreting cells (ASC) in human nasal polyps (NP), mucosal tissues rich in ASC without germinal centers (GC).

One-Stop Serum Assay Identifies COVID-19 Disease Severity and Vaccination Responses.

SARS-CoV-2 has caused over 100,000,000 cases and almost 2,500,000 deaths globally. Comprehensive assessment of the multifaceted antiviral Ab response is critical for diagnosis, differentiation of severity, and characterization of long-term immunity, especially as COVID-19 vaccines become available. Severe disease is associated with early, massive plasmablast responses.

Longitudinal trends using a point-of-care gelatin-based model for ultrasound-guided central venous catheter insertion.

Ultrasound (US)-guided central venous catheter (CVC) insertion is a procedure that carries the risk of significant complications. Simulation provides a safe learning atmosphere, but most CVC simulators are not available outside of simulation centers. To explore longitudinal trends in US-guided CVC insertion competency in internal medicine (IM) interns, we studied the use of a low-fidelity, gelatin-based, US-guided CVC insertion simulation model combined with a simulation curriculum.

Checklists Improve Team Performance During Simulated Extracorporeal Membrane Oxygenation Emergencies: A Randomized Trial.

Unlabelled: Extracorporeal membrane oxygenation-related complications are potentially catastrophic if not addressed quickly. Because complications are rare, high-fidelity simulation is recommended as part of the training regimen for extracorporeal membrane oxygenation specialists. We hypothesized that the use of standardized checklists would improve team performance during simulated extracorporeal membrane oxygenation emergencies.

Elevated SARS-CoV-2 Antibodies Distinguish Severe Disease in Early COVID-19 Infection.

Background: SARS-CoV-2 has caused over 36,000,000 cases and 1,000,000 deaths globally. Comprehensive assessment of the multifaceted anti-viral antibody response is critical for diagnosis, differentiation of severe disease, and characterization of long-term immunity. Initial observations suggest that severe disease is associated with higher antibody levels and greater B cell/plasmablast responses.

Relaxed peripheral tolerance drives broad autoreactivity in severe COVID-19.

An emerging feature of COVID-19 is the identification of autoreactivity in patients with severe disease that may contribute to disease pathology, however the origin and resolution of these responses remain unclear. Previously, we identified strong extrafollicular B cell activation as a shared immune response feature between both severe COVID-19 and patients with advanced rheumatic disease. In autoimmune settings, this pathway is associated with relaxed peripheral tolerance in the antibody secreting cell compartment and the generation of autoreactive responses.

Extrafollicular B cell responses correlate with neutralizing antibodies and morbidity in COVID-19.

A wide spectrum of clinical manifestations has become a hallmark of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, although the immunological underpinnings of diverse disease outcomes remain to be defined. We performed detailed characterization of B cell responses through high-dimensional flow cytometry to reveal substantial heterogeneity in both effector and immature populations. More notably, critically ill patients displayed hallmarks of extrafollicular B cell activation and shared B cell repertoire features previously described in autoimmune settings.