Discrepancies between two total IgE assays and difference in reference intervals in healthy adults.

Objective: To compare total immunoglobulin (Ig) E assay performance characteristics between Abbott Architect and Siemens Immulite test systems. Reference intervals were also determined for both platforms in an American population of healthy adults.

Methods: Agreement of the two total IgE assays was evaluated in a cohort of 331 subjects with normal complete blood count (CBC) and comprehensive metabolic panel (CMP) results.

Myeloperoxidase Staining Identifies Endothelial Injury of Peritubular Capillaries and Glomeruli in Renal Antibody-Mediated Rejection.

Objective: It remains unclear if C4d staining is related to any peritubular and glomerular injury during antibody mediated rejection (ABMR). The goal of this study was to determine if myeloperoxidase (MPO) staining can highlight endothelial injury in peritubular capillaries (PTC) and glomeruli.

Methods: The study included 12 native negative controls, 19 transplant biopsies with borderline changes (BC) as transplant controls, and one group of renal transplant biopsies with ABMR as the study group (acute/chronic, n=22).

Immune responses of lung transplant recipients against SARS-CoV-2 and common respiratory coronaviruses: Evidence for pre-existing cross-reactive immunity.

Humoral and cellular immune responses to SARS-CoV-2 and other coronaviruses in lung transplant recipients are unknown. We measured antibodies and T cell responses against the SARS-CoV-2 spike S2 and nucleocapsid antigens and spike antigens from common respiratory coronaviruses (229E, NL63, OC43, and HKU1) after vaccination or infection of LTxRs. 148 LTxRs from single center were included in this study: 98 after vaccination and 50 following SARS-CoV-2 infection.

Dried blood spots are a valid alternative to venipuncture for COVID-19 antibody testing.

Background: Serologic analysis is an important tool towards assessing the humoral response to COVID-19 infection and vaccination. Numerous serologic tests and platforms are currently available to support this line of testing. Two broad antibody testing categories are point-of-care lateral flow immunoassays and semi-quantitative immunoassays performed in clinical laboratories, which typically require blood collected from a finger-stick and a standard venipuncture blood draw, respectively.

Predictors of hospitalization and severe disease due to breakthrough SARS-CoV-2 infection in fully vaccinated individuals.

Objective: We aimed to identify risk factors for hospital admission and severe disease among fully vaccinated (FV) individuals with COVID-19. Further, we investigated if risk factors for hospitalization and severe disease are similar between unvaccinated (UV) and vaccinated individuals.

Methods: This was a multicenter, observational cohort analysis from a large regional healthcare system in metro Detroit using electronic health record data to evaluate risk factors for hospitalization and severe COVID-19 disease.

Prognostic Value of SARS-CoV-2 Anti-RBD IgG Antibody Quantitation on Clinical Outcomes in Hospitalized COVID-19 Patients.

Background: Antibody levels against SARS-CoV-2 can be used as an indicator of recent or past vaccination or infection. However, the prognostic value of antibodies targeting the receptor binding protein (anti-RBD) in hospitalized patients is not widely reported.

Purpose: Determine prognostic impact of SARS-CoV-2 antibody quantification at the time of admission on clinical outcomes in hospitalized COVID-19 patients.

Clinical and analytical evaluation of the Abbott AdviseDx quantitative SARS-CoV-2 IgG assay and comparison with two other serological tests.

Introduction: Serological testing is an important tool to assist with assessing the immune response to SARS-CoV-2 infections, the causative agent of COVID-19. A quantitative assay was recently developed by Abbott Laboratories to measures antibodies against the receptor binding domain of the spike protein. In addition to assessing disease prevalence, this assay is useful towards determining the scale and duration of the humoral response to infection and vaccination.

Vaccination reduces need for emergency care in breakthrough COVID-19 infections: A multicenter cohort study.

Background: While recent literature has shown the efficacy of the SARS-CoV-2 vaccine in preventing infection, it's impact on need for emergency care/hospitalization in breakthrough infections remain unclear, particularly in regions with a high rate of variant viral strains. We aimed to determine if vaccination reduces hospital visits in breakthrough COVID-19.

Methods: This observational cohort analysis compared unvaccinated (UV), partially vaccinated (PV), and fully vaccinated (FV) adult patients with SARS-CoV-2 infection requiring emergency care(EC)/hospitalization within an eight-hospital system in Michigan.

Longitudinal characterization of the IgM and IgG humoral response in symptomatic COVID-19 patients using the Abbott Architect.

Background: Antibody testing has recently emerged as an option to assist with determining exposure to SARS-CoV-2, the causative agent of COVID-19. Elucidation of the kinetics and duration of the humoral response is important for clinical management and interpreting results from serological surveys.

Objectives: Here we evaluated the clinical performance of Abbott SARS-CoV-2 IgM and IgG assays, as well as the longitudinal dynamics of the antibody response in symptomatic COVID-19 patients.

Coronavirus Disease 2019 (COVID-19) Seropositivity and Asymptomatic Rates in Healthcare Workers Are Associated with Job Function and Masking.

Background: Although the risk of exposure to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is higher for frontline healthcare workers, not all personnel have similar risks. Determining infection rate is difficult due to the limits on testing and the high rate of asymptomatic individuals. Detection of antibodies against SARS-CoV-2 may be useful for determining prior exposure to the virus and assessing mitigation strategies, such as isolation, masks, and other protective equipment.

CCDC22 deficiency in humans blunts activation of proinflammatory NF-κB signaling.

NF-κB is a master regulator of inflammation and has been implicated in the pathogenesis of immune disorders and cancer. Its regulation involves a variety of steps, including the controlled degradation of inhibitory IκB proteins. In addition, the inactivation of DNA-bound NF-κB is essential for its regulation.

COMMD1 (copper metabolism MURR1 domain-containing protein 1) regulates Cullin RING ligases by preventing CAND1 (Cullin-associated Nedd8-dissociated protein 1) binding.

Cullin RING ligases (CRLs), the most prolific class of ubiquitin ligase enzymes, are multimeric complexes that regulate a wide range of cellular processes. CRL activity is regulated by CAND1 (Cullin-associated Nedd8-dissociated protein 1), an inhibitor that promotes the dissociation of substrate receptor components from the CRL. We demonstrate here that COMMD1 (copper metabolism MURR1 domain-containing 1), a factor previously found to promote ubiquitination of various substrates, regulates CRL activation by antagonizing CAND1 binding.

A bimolecular affinity purification method under denaturing conditions for rapid isolation of a ubiquitinated protein for mass spectrometry analysis.

Ubiquitination can have profound effects on the stability and function of cellular proteins. Mass spectrometry (MS) can be used to map the specific amino acid residues that are conjugated to ubiquitin in a target protein. However, the purification required for proteomic analysis can be challenging.

Bimolecular affinity purification (BAP): tandem affinity purification using two protein baits.

The tandem affinity purification (TAP) procedure was pioneered in yeast for the purpose of purifying and characterizing protein complexes. While affinity purification is relatively easy to perform, nonspecific protein interactions can plague the identification of true interacting partners of the given bait utilized in the purification. To alleviate this problem, two sequential affinity purification steps are employed in the TAP procedure.

GCN5 is a required cofactor for a ubiquitin ligase that targets NF-kappaB/RelA.

The transcription factor NF-kappaB is a critical regulator of inflammatory and cell survival signals. Proteasomal degradation of NF-kappaB subunits plays an important role in the termination of NF-kappaB activity, and at least one of the identified ubiquitin ligases is a multimeric complex containing Copper Metabolism Murr1 Domain 1 (COMMD1) and Cul2. We report here that GCN5, a histone acetyltransferase, associates with COMMD1 and other components of the ligase, promotes RelA ubiquitination, and represses kappaB-dependent transcription.

Nuclear-cytosolic transport of COMMD1 regulates NF-kappaB and HIF-1 activity.

Copper metabolism MURR1 domain1 (COMMD1) is a novel inhibitor of the transcription factors NF-kappaB and HIF-1, which play important roles in inflammation and tumor growth, respectively. In this study, we identified two highly conserved nuclear export signals (NESs) in COMMD1 and revealed that these NESs were essential and sufficient to induce maximal nuclear export of COMMD1. Inhibition of CRM1-mediated nuclear export by Leptomycin B resulted in nuclear accumulation of COMMD1.

COMMD1 expression is controlled by critical residues that determine XIAP binding.

COMMD {COMM [copper metabolism Murr1 (mouse U2af1-rs1 region 1)] domain-containing} proteins participate in several cellular processes, ranging from NF-kappaB (nuclear factor kappaB) regulation, copper homoeostasis, sodium transport and adaptation to hypoxia. The best-studied member of this family is COMMD1, but relatively little is known about its regulation, except that XIAP [X-linked IAP (inhibitor of apoptosis)] functions as its ubiquitin ligase. In the present study, we identified that the COMM domain of COMMD1 is required for its interaction with XIAP, and other COMMD proteins can similarly interact with IAPs.

COMMD proteins and the control of the NF kappa B pathway.

The COMM domain containing (COMMD) family of proteins represents a recently discovered set of evolutionarily conserved factors characterized by the presence of a defining carboxy-terminal motif. In vertebrates, there are ten members of the family, and among their emerging functions the control of the transcription factor NFkappaB has been most extensively studied. NFkappaB plays a critical role in a number of homeostatic processes in multicellular organisms, including the regulation of immunity and cell survival.

COMMD1 promotes the ubiquitination of NF-kappaB subunits through a cullin-containing ubiquitin ligase.

NF-kappaB is a pleiotropic transcription factor involved in multiple processes, including inflammation and oncogenesis. We have previously reported that COMMD1 represses kappaB-dependent transcription by negatively regulating NF-kappaB-chromatin interactions. Recently, ubiquitination of NF-kappaB subunits has been similarly implicated in the control of NF-kappaB recruitment to chromatin.

Early vaccination with tumor-lysate-pulsed dendritic cells after allogeneic bone marrow transplantation has antitumor effects.

Allogeneic bone marrow transplantation (BMT) remains the primary treatment for many hematologic malignancies but has had limited success against solid tumors. The antitumor activity of this treatment approach involves the tumoricidal activity of chemoradiation and the additive graft-versus-tumor activity of donor T cells. However, even with current protocols, some tumors develop resistance and become unresponsive to current therapeutic regimens.

COMMD proteins, a novel family of structural and functional homologs of MURR1.

MURR1 is a multifunctional protein that inhibits nuclear factor kappaB (NF-kappaB), a transcription factor with pleiotropic functions affecting innate and adaptive immunity, apoptosis, cell cycle regulation, and oncogenesis. Here we report the discovery of a new family of proteins with homology to MURR1. These proteins form multimeric complexes and were identified in a biochemical screen for MURR1-associated factors.