Publications by authors named "Michael S Abers"

Article Synopsis
  • - Mutations in the RAC2 protein are linked to various immune disorders in patients, including neonatal SCID and infantile diseases resembling leukocyte adhesion deficiency, with 15 new mutations identified among 54 patients studied.
  • - The study highlighted that different types of mutations in RAC2 influenced disease outcomes; for instance, certain mutations led to neonatal SCID while others caused later-onset combined immune deficiency or LAD-like diseases.
  • - Clinical analysis revealed significant immune system issues among affected patients, including low levels of T and B cells, recurrent infections, and abnormalities in neutrophil function, indicating severe impacts on their immune response.
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  • Elderly patients with severe COVID-19 showed reduced T-cell diversity and weaker immune responses compared to younger patients, highlighting age-related vulnerabilities in fighting the virus.
  • The study used advanced sequencing techniques to analyze T-cell responses in both COVID-19 patients and individuals with inborn errors of immunity who received an mRNA vaccine, revealing specific genetic associations affecting these responses.
  • Findings indicated that mRNA vaccines successfully enhanced the T-cell responses in individuals with immune deficiencies, suggesting their effectiveness even in populations that struggle to develop strong immune responses on their own.
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  • CD4 T helper 17 (T17) cells play a dual role in protecting barrier tissues and contributing to autoimmune conditions, like multiple sclerosis.* -
  • The transcription factor EGR2 is crucial for driving the harmful behavior of pathogenic T17 cells in the central nervous system (CNS), while it does not affect protective T17 cells elsewhere.* -
  • Deleting EGR2 specifically in T cells reduces neuroinflammation without impairing the body's ability to fight infections, highlighting its role in regulating T17 cell functions based on tissue and disease context.*
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  • - A study examined 22 patients with CTLA-4 insufficiency who contracted COVID-19 between 2020 and 2022, revealing that most had mild symptoms like fever and cough, with an average illness duration of 7.5 days.
  • - Out of the participants, 91% were treated as outpatients, while only 2 were hospitalized for pneumonia, and several received monoclonal antibody treatment and vaccinations without severe side effects.
  • - The study found that all patients tested negative for autoantibodies against type 1 interferons (IFNs), suggesting that CTLA-4 insufficiency does not significantly increase the risk of severe COVID-19 in this group.
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Systemic candidiasis is a common, high-mortality, nosocomial fungal infection. Unexpectedly, it has emerged as a complication of anti-complement C5-targeted monoclonal antibody treatment, indicating a critical niche for C5 in antifungal immunity. We identified transcription of complement system genes as the top biological pathway induced in candidemic patients and as predictive of candidemia.

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  • Subcutaneous phaeohyphomycosis usually affects healthy individuals after trauma but can become severe in people with CARD9 deficiencies or those who have had transplants due to unclear protective mechanisms.
  • A patient with a severe case of this infection harbored harmful mutations in the CLEC7A gene, leading to impaired immune responses against the fungus Corynespora cassiicola.
  • Research using a mouse model revealed that both Dectin-1 and CARD9 are crucial for producing key immune signals (TNF-α and IL-1β) that help kill this fungus, and a study of additional patients showed that many had similar mutations affecting immune function.
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Type-I interferons (IFNs) mediate antiviral activity and have emerged as important immune mediators during coronavirus disease 19 (COVID-19). Several lines of evidence suggest that impaired type-I IFN signaling may predispose to severe COVID-19. However, the pathophysiologic mechanisms that contribute to illness severity remain unclear.

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Immune and inflammatory responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) contribute to disease severity of coronavirus disease 2019 (COVID-19). However, the utility of specific immune-based biomarkers to predict clinical outcome remains elusive. Here, we analyzed levels of 66 soluble biomarkers in 175 Italian patients with COVID-19 ranging from mild/moderate to critical severity and assessed type I IFN-, type II IFN-, and NF-κB-dependent whole-blood transcriptional signatures.

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Article Synopsis
  • - The study analyzed 987 patients with severe COVID-19 pneumonia and found that 101 patients had neutralizing autoantibodies (auto-Abs) against interferon-ω and various types of interferon-α at the onset of the disease.
  • - These auto-Abs interfere with the ability of type I interferons to combat SARS-CoV-2 infection in laboratory tests, but they were absent in people with mild infections and very rare in healthy individuals.
  • - The presence of these auto-Abs is linked to life-threatening COVID-19 pneumonia and appears to affect 2.6% of women and 12.5% of men, indicating a significant gender difference in this autoimmune response.
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Neutrophils employ several mechanisms to restrict fungi, including the action of enzymes such as myeloperoxidase (MPO) or NADPH oxidase, and the release of neutrophil extracellular traps (NETs). Moreover, they cooperate, forming "swarms" to attack fungi that are larger than individual neutrophils. Here, we designed an assay for studying how these mechanisms work together and contribute to neutrophil's ability to contain clusters of live Candida.

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The clearance of both tumors and microbes depends on highly coordinated immune responses that are sufficiently potent to kill malignant or microbial cells while avoiding immunopathology from an overly exuberant inflammatory response. A molecular understanding of the immune pathways that regulate these responses paved the way for the development of checkpoint inhibitors (CPIs) as a therapeutic strategy to boost endogenous antitumor immunity. CPIs have demonstrated survival benefits across a wide spectrum of cancers.

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The mammalian immune system has evolved the capacity to detect and destroy tumor cells. Tumors utilize multiple strategies to evade host immune surveillance, including the induction of the checkpoint molecules cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1) to suppress antitumor immunity. Pharmacologic blockade of these molecules with checkpoint inhibitors (CPIs) restores T cell function and prolongs survival in patients with various malignancies.

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Before 1945, Streptococcus pneumoniae caused more than 90% of cases of pneumonia in adults. After 1950, the proportion of pneumonia caused by pneumococcus began to decline. Pneumococcus has continued to decline; at present, this organism is identified in fewer than fewer10%-15% of cases.

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Background: Procalcitonin (PCT) is a prohormone that rises in bacterial pneumonia and has promise in reducing antibiotic use. Despite these attributes, there are inconclusive data on its use for clinical prognostication. We hypothesize that serial PCT measurements can predict mortality, intensive care unit (ICU) admission, and bacteremia.

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Prolonged neutropenia is generally thought to be the major factor for invasive pulmonary aspergillosis (IPA). In the present study, we characterize the frequency, severity, and duration of neutropenia that immediately precedes IPA. Prolonged neutropenia was identified in only one third of all IPA cases and occurred exclusively in hematologic patients.

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Abnormal movements are frequently encountered in patients with brain injury hospitalized in intensive care units (ICUs), yet characterization of these movements and their underlying pathophysiology is difficult due to the comatose or uncooperative state of the patient. In addition, the available diagnostic approaches are largely derived from outpatients with neurodegenerative or developmental disorders frequently encountered in the outpatient setting, thereby limiting the applicability to inpatients with acute brain injuries. Thus, we reviewed the available literature regarding abnormal movements encountered in acutely ill patients with brain injuries.

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Background: Postobstructive community-acquired pneumonia (PO-CAP) is relatively common in clinical practice. The clinical syndrome is poorly defined, and the role of infection as a cause of the infiltrate is uncertain. We prospectively studied patients with PO-CAP and compared them to a cohort of patients with bacterial community-acquired pneumonia (B-CAP).

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