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.

Viral Load Suppression in People Living with HIV Before and During the COVID-19 Pandemic in Brooklyn, New York.

Consistent care is crucial for the health maintenance of people living with human immunodeficiency virus (HIV) (PWH). The coronavirus 2019 (COVID-19) epidemic disrupted patient care in New York City (NYC), yet few studies investigated the association between COVID-19 and viral load suppression in PWH in NYC. This study aims to assess how the COVID-19 pandemic impacted HIV viral load and CD4 + T-cell counts in PWH. Medical records of 1130 adult HIV patients who visited the Special Treatment and Research Health Center in Brooklyn, NY, between January 2019 and May 2023 were compared across three timeframes (pre-pandemic, January 1, 2019 to December 31, 2019; first pandemic phase, March 19, 2020 to December 31, 2020; and second pandemic phase, January 1, 2021 to May 11, 2023). Demographic and clinical variables (e.g. viral load and CD4 + T cell count) were assessed. About 40% of patients did not have routine laboratory monitoring during the first pandemic phase compared with pre-pandemic. The mean HIV viral load was higher during the second pandemic phase compared with pre-pandemic (p = 0.009). The percentages of patients with undetectable HIV viral load and numbers (mm3) of CD4 + T-cells were similar for all time periods. These findings indicate that the COVID-19 pandemic may have exacerbated challenges for individuals who already had barriers to medication adherence or access. However, most individuals remained consistently on their antiretrovirals throughout the pandemic. Further studies are warranted to determine how to mitigate the impact of future pandemics for the health of PWH.

Neonatal prophylaxis with antibiotic containing ointments does not reduce incidence of chlamydial conjunctivitis in newborns.

BACKGROUND: Neonatal ocular prophylaxis with silver nitrate does not prevent neonatal conjunctivitis due to Chlamydia trachomatis. The efficacy of antibiotic containing preparations for prevention of neonatal chlamydial conjunctivitis (NCC) has not been established. OBJECTIVE: To examine published literature to determine whether antibiotic containing preparation are efficacious for prevention of NCC and C. trachomatis in the nasopharynx. METHODS: A literature search of MEDLINE and EMBASE. Articles were selected for review if their content included 4 key criteria: (1) Prospective/comparative study. (2) Prenatal screening of mothers for C. trachomatis with results reported. (3) Follow-up of infants born to chlamydia-positive women. (4) Infants prospectively followed at regular intervals and tested for C. trachomatis in the eye/ nasopharynx (NP). RESULTS: The search yielded 159 studies; 11 were selected for full reviews, eight were excluded; three addressed the four criteria. Rates of C. trachomatis conjunctivitis in infants in included studies who received silver nitrate was 20-33%; positive NP, 1-28% and pneumonia, 3-8%. Rates of C. trachomatis conjunctivitis in neonates who received erythromycin or tetracycline prophylaxis did not differ from silver nitrate; 0-15 and 11%, respectively, who received erythromycin or tetracycline developed NCC. Similarly, 4-33 and 5% of infants who received erythromycin or tetracycline, respectively, had positive NP cultures; 0-4% developed chlamydial pneumonia. CONCLUSION: Neonatal ocular prophylaxis with erythromycin or tetracycline ophthalmic ointments does not reduce incidence of neonatal chlamydial conjunctivitis or respiratory infection in infants born to mothers with C. trachomatis infection compared to silver nitrate.

Doxycycline suppresses Chlamydia pneumoniae induced interferon-gamma responses in peripheral blood mononuclear cells in children with allergic asthma.

Persistent respiratory infections caused by Chlamydia pneumoniae have been implicated in the pathogenesis of chronic diseases (e.g. asthma). Antibiotics are used to treat C. pneumoniae respiratory infections; however, the use of antibiotics as anti-inflammatory agents in treatment of asthma remains controversial. The current study investigated whether ciprofloxacin, azithromycin, or doxycycline can suppress C. pneumoniae-induced production of immunoglobulin (Ig) E or cytokines in peripheral blood mononuclear cells (PBMC) obtained from asthmatic children. Apart from blood, nasopharyngeal swab specimens were also collected to test for the presence of C. pneumoniae and/or M. pneumoniae (qPCR). PBMC (1.5 x 106) from asthmatic pediatric patients (N = 18) were infected or mock infected for 1 h ± C. pneumoniae AR-39 at a multiplicity of infection (MOI) = 0.1, and cultured ± ciprofloxacin, azithromycin, or doxycycline (0.1 or 1.0 µg/mLmL) for either 48 h (cytokines) or 10 days (IgE). Interleukin (IL)-4, interferon (IFN)-γ and IgE levels in supernatants were measured (ELISA). When PBMC were infected with C. pneumoniae, IL-4 and IFNγ production increased (p = 0.06 and 0.03, respectively); IgE levels were low. The now-elevated levels of IL-4 didn't decrease significantly after addition of ciprofloxacin, azithromycin, or doxycycline. However, infected PBMC IFNγ formation decreased significantly when 0.1 µg/mL doxycycline was employed (p = 0.04); no dose of ciprofloxacin or azithromycin had any impact. This inhibitory outcome with doxycycline lends support to the use of tetracyclines as immune modulators and anti-inflammatory medications in treatment of C. pneumoniae-infected asthma patients.

IgE anti-Haemophilus influenzae type b (Hib) antibodies detected in serum of Hib-vaccinated asthmatic and non-asthmatic pediatric patients.

BACKGROUND: Haemophilus influenzae type b (Hib) bacterium causes severe illness in infants and children, but has largely been eliminated by introducing a universal Hib conjugate vaccine. While effects of certain vaccinations on atopic disease have been studied, little is known about the relationship between Hib vaccination and diseases of altered immunoglobulin E (IgE) regulation (asthma or atopy). As such, it is necessary to provide more evidence concerning Hib vaccination as a possible risk factor for atopic disease. METHODS: Total serum IgE and IgE-and IgG-anti-Hib antibody responses were studied in Hib vaccinated asthmatic (N.=14) and non-asthmatic children (N=26) (VaccZyme™ Human Anti Hib Enzyme Immunoassay Kit). Data are reported as mean optical density (OD) values. RESULTS: We found that: 1) total serum IgE levels were higher in asthmatic compared with non-asthmatic subjects (389±125 vs. 125±129, P<0.001); 2) IgE and IgG anti-Hib antibody responses were similar in both asthmatic and non-asthmatic subjects (0.722±0.279 and 0.681±0.280, respectively; P=0.65; 0.450±0.505 and 0.573±0.779, respectively; P=0.580). CONCLUSIONS: The universal Hib vaccine antigen did not result in either increased IgE, or IgG anti-Hib antibody responses in asthmatic or non-asthmatics subjects. Thus, in this cohort, no association between Hib vaccination and asthma status was identified.

Cost-benefit analysis of Chlamydia trachomatis screening in pregnant women in a high burden setting in the United States.

BACKGROUND: Chlamydia trachomatis is the most common bacterial sexually transmitted infection (STI) in the United States (U.S.) [1] and remains a major public health problem. We determined the cost- benefit of screening all pregnant women aged 15-24 for Chlamydia trachomatis infection compared with no screening. METHODS: We developed a decision analysis model to estimate costs and health-related effects of screening pregnant women for C. trachomatis in a high burden setting (Brooklyn, NY). Outcome data was from literature for pregnant women in the 2015 US population. A virtual cohort of 6,444,686 pregnant women, followed for 1 year was utilized. Using outcomes data from the literature, we predicted the number of C. trachomatis cases, associated morbidity, and related costs. Two comparison arms were developed: pregnant women who received chlamydia screening, and those who did not. Costs and morbidity of a pregnant woman-infant pair with C. trachomatis were calculated and compared. RESULTS: Cost and benefit of screening relied on the prevalence of C. trachomatis; when rates are above 16.9%, screening was proven to offer net cost savings. At a pre-screening era prevalence of 8%, a screening program has an increased expense of $124.65 million ($19.34/individual), with 328 thousand more cases of chlamydia treated, and significant reduction in morbidity. At a current estimate of prevalence, 6.7%, net expenditure for screening is $249.08 million ($38.65/individual), with 204.63 thousand cases of treated chlamydia and reduced morbidity. CONCLUSIONS: Considering a high prevalence region, prenatal screening for C. trachomatis resulted in increased expenditure, with a significant reduction in morbidity to woman-infant pairs. Screening programs are appropriate if the cost per individual is deemed acceptable to prevent the morbidity associated with C. trachomatis.

Relationship of influenza virus infection to associated infections in children who present with influenza-like symptoms.

BACKGROUND: Influenza virus is a major health care burden and is associated with significant morbidity and mortality. Data on morbidity and complications (pneumonia, otitis media) related to influenza virus infection in primary care settings are limited with reports mainly obtained from hospital settings. We assessed the prevalence of complications from viral/bacterial infections in influenza- positive compared with influenza- negative children presenting with influenza-like illness (ILI) in a primary care setting. METHODS: This retrospective, practice-based chart review studied complications from viral/bacterial infections in 255 children and adolescents (females/males, 1-21 years) who presented with ILI. We also compared the prevalence of complications by influenza vaccination status between influenza positive (N = 32/121) and influenza negative (N = 50/134) cases (2013-2015). Comparisons for categorical variables were made using chi-squared tests. RESULTS: The prevalence of complications was similar in influenza positive (18/121) and influenza negative (22/134) patients (P = NS). Patients presenting with ILI, who were vaccinated, were less likely to test positive for influenza compared with patients who were not vaccinated (P = 0.064). However, prevalence of infections was similar in both groups based on vaccination status. We did not find any effect of type of health insurance on influenza status (P > 0.05) CONCLUSION: Common respiratory complications of seasonal influenza did not differ in influenza positive compared with influenza negative patients. Vaccination with influenza vaccine may result in decreased duration or severity of symptoms, and remains an important public health intervention. In primary care settings, determination of influenza status may be an important tool for clinicians to predict the likelihood of complications.

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.

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.

Doxycycline suppresses Chlamydia pneumoniae-mediated increases in ongoing immunoglobulin E and interleukin-4 responses by peripheral blood mononuclear cells of patients with allergic asthma.

OBJECTIVES: Chlamydia pneumoniae, an obligate intracellular bacterium, has been associated with asthma and the induction of immunoglobulin E (IgE) responses. Whereas tetracyclines have anti-chlamydial activity, their effect on human IgE responses to C. pneumoniae has not been studied. METHODS: Peripheral blood mononuclear cells (PBMCs) from serum IgE+ allergic asthmatic subjects (n = 11) and healthy controls (n = 12) were infected with C. pneumoniae and cultured for 12 days with or without doxycycline (0.01-1.0 mg/L). IgE, interferon (IFN)-γ and interleukin (IL)-4 levels in supernatants were determined on days 1-12 post-infection, and C. pneumoniae DNA copy numbers in PBMC culture were measured on day 2 (quantitative PCR). RESULTS: C. pneumoniae-infected PBMCs from allergic asthmatic individuals had increased levels of IgE in supernatants compared with uninfected PBMCs (520% on day 10 post-infection, P = 0.008). IgE levels in PBMC cultures from controls were undetectable (<0.3 ng/mL). Increases in C. pneumoniae-induced IgE in asthmatics correlated with those of C. pneumoniae-induced IL-4 (r = 0.98; P < 0.001), but not with IFN-γ. The addition of doxycycline (1.0 mg/L) to the culture strongly suppressed the production of IgE (>70%, P = 0.04) and IL-4 (75%, P = 0.018), but not IFN-γ. The suppressive effect on IL-4 production remained significant even at concentrations of doxycycline that were subinhibitory (0.01 mg/L) for C. pneumoniae. In both asthmatic participants and controls, no significant effect of doxycycline on DNA copy numbers of C. pneumoniae was observed. CONCLUSIONS: Doxycycline suppressed the C. pneumoniae-induced production of IgE and IL-4, but not IFN-γ, in PBMCs from IgE+ allergic asthmatic subjects. These findings resulted from the immunomodulatory anti-allergic properties of tetracyclines.

Effect of filgrastim (recombinant human granulocyte colony stimulating factor) on IgE responses in human asthma: a case study.

RATIONALE: The role of peripheral blood progenitor cell mobilization on Immunoglobulin E (IgE) responses has not been studied. METHODS: Distributions of blood lymphocytes (CD4+, CD8+, CD8+CD60+, CD19+, CD23+, CD16/56+, CD25, CD45RA+, CD45RO+, CD34+), and levels of serum immunoglobulins (IgM, IgG, IgA, IgE) were studied in an allergic asthmatic serum IgE+ (181IU/mL) adult (m/45 y/o) donor undergoing routine stem cell mobilization protocol (American Society of Hematology) before (day-30), during (day 4), and after (1 wk post last dose) filgrastim (subcutaneous, 480 mcg, 2qd) treatment (flow cytometry, nephelometry, UniCAP Total IgE Fluoro enzyme immunoassay). RESULTS: On day 4 of filgrastim treatment, numbers of CD8+CD60+T cells and CD23+ blood cells dramatically increased (98% and 240% respectively) compared with pre treatment. In contrast on day 4 of treatment, serum IgE levels decreased (>50%) compared with pre treatment. CD8+CD60+T cells and CD23+ blood cells and serum IgE levels approached pre-treatment levels at 1 week post treatment. CONCLUSIONS: Filgrastim treatment transiently increases numbers of CD8+CD60+T and CD23+ expressing cells, which are known to regulate human IgE responses, while also transiently suppressing ongoing IgE responses. These results suggest that filgrastim affects IgE related responses, and may be useful in modulating allergic responses.

Serum Immunoglobulin Levels as Potential Biomarkers of COVID-19 Pneumonia.

OBJECTIVE: Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has been known to cause immune dysregulation. However, the association between specific immunoglobulins and clinical characteristics in COVID-19 remains poorly understood. This study investigated the relationship between immunoglobulins and clinical outcomes in adults hospitalized with COVID-19 pneumonia. METHODS: A retrospective chart analysis was performed (N=569, December 2020-April 2021). Information on demographics, clinical factors, and total serum immunoglobulin (IgG, IgA, IgM, and IgE) levels were collected (N=60). Clinical outcomes of interest included: symptom duration, comorbidities (Charlson 10-year-estimated-survival (C10YES) and comorbidity index (CCI), vital derangements upon presentation (NEWS-2-score), length of stay (LOS), and mortality. Spearman correlation, chi-square tests and linear regression were conducted. RESULTS: Serum IgM levels were positive predictors of C10YES (ß=0.104, p=0.023) and negative predictors of CCI (ß=-0.007, p=0.047). There was an association between higher serum IgG levels and longer LoS (ß=7.455, p=0.047). We found no significant associations between immunoglobulins and preadmission symptom duration, medication use, or mortality. CONCLUSIONS: Total IgM was associated with increased survival and decreased comorbidity, and total IgG was associated with length of hospitalization. IgM may predict the body's initial ability to produce humoral immune responses, and IgG may function as a possible signature of chronic antigenic responses and inflammation, associated with comorbidities that increase COVID-19 hospitalization. Evaluating total IgM and IgG as prognostic biomarkers in COVID-19 pneumonia patients may contribute to improved management and clinical outcomes.

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.