Idiopathic Hypereosinophilic Syndrome in a Professional Athlete.

OBJECTIVE: To present the case of an athlete with hypereosinophilic syndrome (HES). CASE REPORT: We present a 25-year-old female athlete, with no significant past medical history, who had a two-month history of progressive dry cough, wheezing, exertional dyspnea, and chest pain. Physical examination revealed patient to be febrile to 101.6 degrees Fahrenheit and tachycardic to 120 beats per minute with new leukocytosis of 35.9x109/L and eosinophilia of 24,000/µL. She was also found to have elevated troponins ~1.5 ng/mL and creatine kinase (CK) 203 U/L. Her overall clinical picture was concerning for hypereosinophilic syndrome with multiorgan system involvement. CONCLUSION: Findings endorse the diagnosis of HES. HES is a rare condition that is difficult to diagnose. Early clinical diagnostic signs of HES may include fatigue, cough, breathlessness, and fever.

Phosphorylated p38 MAP kinase expression by leucocytes is increased in allergic humans and associated with IgE responses.

Mitogen-activated protein kinases (MAPK) activate cascades that regulate cell proliferation, differentiation and death. Phosphorylated (phos-)p38 MAPK is a cell-signalling pathway associated with Th2 cytokine responses, which is required for immunoglobulin (Ig)E production. It is unknown whether MAPK are associated with IgE production. We examine the evidence linking p38 MAPK to inflammatory responses. Phos-p38, extracellular signal-related kinase (ERK) and c-JUN-n terminal (JNK) MAPK expression by blood leucocyte subsets and levels of serum Igs were measured in blood from adults with asthma and/or rhinoconjunctivitis (N = 28) and non-asthma (N = 10) (flow cytometry, microfluorenzymeimmunoassay). Peripheral blood mononuclear cells (PBMC) from allergic subjects were cultured for 10 days ± anti-CD40/recombinant IL-4 ± inhibitor of phos-P38. Culture supernatants were assayed for IgE (ELISA). Phos-p38 MAPK expression by all leucocyte subsets of allergic subjects was associated with serum IgE levels (p ≤ 0.01), after adjusting for cell counts, age, sex, race and smoking status (p ≤ 0.04). Leucocyte expression of phos-ERK and JNK did not correlate with IgE (p = 0.09-0.99). Instead, phos-ERK expression was associated with serum IgG. When PBMC from atopic subjects were cultured for 10 days with anti-CD40/rhIL-4, IgE levels were 26.2 ± 18 ng/mL. Inclusion of SB202190 (5-20 µg/mL), a specific inhibitor of phos-p38 MAPK, in culture suppressed IgE production in dose-dependent manner, with peak suppression obtained with SB202190 at 20 µg/mL (82.1% ± 11.8) (p = 0.0001), with virtually no cytotoxicity (<5%). Different MAPK pathways may be associated with IgE (p38) and IgG (ERK) responses. Phos-p38 MAPK can be a potential anti-allergy drug target.

Social determinants of health disparities in Staten Island compared with Manhattan, Queens, Brooklyn, and the Bronx: Contribution to COVID-19 outcomes.

INTRODUCTION: Social determinants of health (SDH) negatively affected Coronavirus disease-2019 (COVID-19) outcomes within the five boroughs of New York City. The goal of this study was to determine whether differences in social demographics within the borough of Staten Island, compared with the other four boroughs, may have contributed to poor COVID-19 outcomes in Staten Island. METHODS: Data were obtained from public data sources. Social demographics obtained included age, household income, poverty status, and education level. COVID-19 infection, hospitalization, and death rates reported from Staten Island were compared with rates from Manhattan, Queens, Brooklyn, and the Bronx (February 29, 2020-October 31, 2022). Mean differences in case rates of COVID-19 were higher in Staten Island compared to all four boroughs. RESULTS: Mean differences in hospitalization and death rates were higher than Manhattan but similar to the other four boroughs. Within Staten Island, case rates were highest in zip codes 10306 and 10309. Hospitalization and death rates were highest in Staten Island zip code 10304. We found that the zip codes of Staten Island with poorer COVID-19 outcomes had more individuals with less than a high school degree, lower mean household income, higher proportion of households earning less than $25,000 a year, and a greater proportion of individuals using public transportation. CONCLUSION: Differences in COVID-19 infection, hospitalization, and death rates exist between the five boroughs and between the 12 zip codes within Staten Island. These differences in COVID-19 outcomes can be attributed to different SDH.

Chlamydia pneumoniae-immunoglobulin E antibody responses in serum from children with asthma.

Chlamydia pneumoniae is an obligate intracellular bacterium that causes respiratory infections in humans. An association between persistent C. pneumoniae infection and asthma pathogenesis has been described. It is unknown whether specific immunoglobulin E (IgE) is a marker of persistent immune activation responses. Therefore, the association between C. pneumoniae-specific-IgE antibodies (Abs) and interferon (IFN)-gamma produced by C. pneumoniae-stimulated peripheral blood mononuclear cells (PBMC) was examined. Blood was collected and serum separated. PBMC from 63 children with or without stable asthma (N = 45 and 18, respectively) were infected or not infected with C. pneumoniae AR-39 and cultured for up to 7 days. Supernatants were collected, and IFN-gamma levels measured (ELISA). Serum C. pneumoniae-IgE Abs were detected by immunoblotting. C. pneumoniae-IgE Abs were detected in asthmatics (27%), compared with non-asthmatics (11%) (P = NS). IFN-gamma responses were more prevalent among asthmatics who had positive C. pneumoniae-IgE Abs (60%) compared with asthmatics without C. pneumoniae-IgE Abs (20%) (P = 0.1432). IFN-gamma responses in C. pneumoniae-stimulated PBMC from children with asthma were more frequent in children who had specific anti-C. pneumoniae-IgE Abs compared to those who did not. This immune response may reflect persistent infection, which may contribute to ongoing asthma symptoms.

CD4+ T effector memory cell responses in Chlamydia pneumoniae-stimulated peripheral blood mononuclear cells in nonasthmatic subjects.

Chlamydia pneumoniae (C. pneumoniae) is a gram-negative intracellular bacterium that causes respiratory infection in humans, including subjects with or without asthma. C. pneumoniae activates cells (e.g., monocytes/macrophages) in vitro, and produces cytokines that may contribute to inflammatory responses observed in asthma. Immunological differences exist between subjects with or without asthma, with regard to host responses to C. pneumoniae. The heterogeneity and subsequent diverse pathophysiology of asthma can be better understood by analyzing the repertoire of T-cell subpopulations; the most common distinction between different asthma endotypes includes cytokines produced by CD4+  cells (T helper (Th)2 high vs. Th2 low).

The Role of Inflammasomes in Mediating Urological Disease: A Short Literature Review.

Inflammasome dysfunction may be responsible for underlying inflammatory diseases, which include renal and urological pathologies. Five inflammasomes have been described, including nucleotide-binding domain leucine-rich repeat (NLR), NL pyrin domain containing receptor 1(NLPR1), NLRP3, NLR and caspase recruitment domain containing receptor 4 (NLRC4), and the AIM2-like receptor. The purpose of this study was to review literature sources regarding how innate immunity and inflammasomes contribute to urologic disease and infection. A literature search of PubMed/MEDLINE, EMBASE and Google Scholar articles. Articles were selected for review if their content included (1) inflammasomes and (2) urology in the adult population. The initiation of specific cytokine cascades, which include IL-1ß and IL-18, appear responsible for a repertoire of urologic pathologies. Inflammation mediates a wide range of uropathies (urologic disorders and infections) which are found in the bladder, prostate, or kidney and inflammasomes appear to be particularly responsible for urological and renal pathologies. Understanding the role of inflammasomes in urologic disorders can help improve treatment and overall quality of life in patients with these disorders.

Intracellular Adhesion Molecule-1 (ICAM-1) Levels in Convalescent COVID-19 Serum: A Case Report.

OBJECTIVE: Intercellular adhesion molecule-1 (ICAM-1), an endothelial cell adhesion molecule, contributes to inflammation and immune-mediated responses. Viral infection of endothelial cells caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can cause vascular changes and elevate the expression of ICAM-1 in coronavirus disease 2019 (COVID-19) patients and may be used as a biomarker to measure disease severity or recovery. This study sought to identify the ICAM-1 levels in convalescent COVID-19 serum 2 to 33 weeks after the initial diagnosis. METHODS: ICAM-1 levels were measured 2-33 weeks after COVID-19 diagnosis (April 2020) in the serum from a subject in Brooklyn, New York who recovered from COVID-19 (ELISA). SARS-CoV-2 IgG antibody levels were also measured (ELISA). RESULTS: ICAM-1 levels were low 2 weeks after the initial COVID-19 diagnosis and increased 6-fold at 5 weeks. ICAM-1 levels decreased at 12 weeks (50%) and at 33 weeks (50%) after the initial COVID-19 diagnosis. SARS-CoV-2 IgG antibody levels were detected 4-5 weeks after the initial COVID-19 diagnosis. CONCLUSIONS: ICAM-1 levels in serum from a recovered COVID-19 patient were highest 5 weeks after the initial COVID-19 diagnosis. The presence of high levels of soluble markers such as ICAM-1, as measured by the anti-ICAM-1 antibody, may be due to their increased shedding from the cell surface. ICAM-1 may also be a prognostic indicator for late complications or sequelae due to COVD-19 infection.

Comparison of Mycoplasma pneumoniae IgM and IgE Antibody Levels in Asthmatic and Non-Asthmatic Adults.

OBJECTIVE: Mycoplasma pneumoniae (M. pneumoniae), an extracellular pathogen lacking a cell wall, causes respiratory infection in adults and children and has been implicated in asthma exacerbation; immunoglobulin (Ig) E may be involved in these exacerbations. Specific IgM and IgG immune response to M. pneumoniae has been reported, but less is known about IgE M. pneumoniae antibody (Ab) responses in asthma. Previous studies in our laboratory demonstrated that asthmatic children have increased IgM M. pneumoniae levels, but not IgE. Thus, we sought to investigate whether past M. pneumoniae infection triggers production of M. pneumoniae-specific IgE Abs in adult subjects with/without asthma. METHODS: M. pneumoniae- IgE and -IgM Ab responses were studied in adult asthmatic (N=22) and non-asthmatic (N=22) subjects (ELISA). Data are reported as antibody index. Threshold detection levels: IgE, IgM: 0.2, 0.9, respectively. RESULTS: M. pneumoniae-IgE Ab levels were low and below the threshold of detection in both asthmatic and non-asthmatics (0.002±0.008 vs. 0.02±0.03; P=0.021). However, specific-IgM levels were slightly higher in non-asthmatics compared with asthmatics (0.96±0.37 vs. 0.79±0.31; P=0.054). M. pneumoniae-IgM Ab positivity was similar in both groups (P=1.0). CONCLUSION: IgM M. pneumoniae Abs may play an important role in non-asthma and persist for months after acute infection. IgE M. pneumoniae Abs may play a less important role in both groups.