Elevated Titers Research Articles

Narcolepsy type 1 and Sydenham chorea – Report of 3 cases and review of the literature

Objectives/backgroundNarcolepsy type 1 (NT1) is an immune-mediated disorder characterized by excessive daytime sleepiness, cataplexy, low levels of hypocretin-1 in the cerebrospinal fluid, and a strong association with the HLA DQB1*06:02 allele. There is evidence for streptococcal infections as one pathogenic factor that may lead to NT1 as part of a multifactorial pathogenesis. Elevated titers of Antistreptolysin-O antibodies and increased inflammatory activity in response to streptococci antigens have been described in patients with NT1. Sydenham chorea (SC) results from a post-streptococcal autoimmune process targeting basal ganglia neurons. Despite this common trigger, SC has been interpreted as a misdiagnosis in a few described cases of patients who were first diagnosed with SC and later with NT1. Our goal was to analyze the association between SC and NT1. Patients/methodsWe reviewed the literature and report three patients from three European sleep centers who were diagnosed with both SC and NT1 within a few months. ResultsWe describe the cases of one male (age 10) and two female (age 22 and 10) patients. ConclusionsWe argue that in those cases both diagnoses are justified, unlike reports of previous cases in which SC was considered a misdiagnosis in patients with NT1. It remains, however, unclear if the conditions occur independently or if there is an overlap disorder- an SC-like subtype of narcolepsy with a particular sequence of symptoms. Further studies need to clarify the causality of the relationship and the pathophysiology of the reported rare association.

Study on genotyping and coinfection rate of human parvovirus 4 among the HTLV-I/II infected blood donors in Khorasan Razavi, Iran

BackgroundHuman Parvovirus 4 (PARV4) is an emerging virus infecting individuals with other blood-borne diseases. This study aimed to determine the prevalence of PARV4 in confirmed HTLVI/II positive samples from blood donors, assessing PARV4 viral load (DNA) and genotyping. Methods: A novel qReal-Time PCR, based on a plasmid construct, was developed to simultaneously detect all three PARV4 genotypes using in-house primers and probes. Positive qPCR samples were subjected to nested PCR amplification and subsequent sequencing. Phylogenetic trees were constructed using the Neighbor-joining (N.J.) method. Results: The coinfection rate of PARV4-DNA in HTLVI/II confirmed infected donors, who were previously deferred, was 14.4 % (13 out of 90), with no observed association with donation status (p = 1.0).Phylogenetic analysis indicated that PARV4-positive samples closely resembled genotype 2 in Iran.qPCR quantification demonstrated significant PARV4 viral loads in positive samples, ranging between 104 and 106 DNA copies/mL of serum. Conclusion: This study presents the first evaluation of HTLVI/II and PARV4coinfection rates among blood donors. Notably, elevated PARV4-DNA titers were detected in HTLVI/II-positive donors. Given PARV's resistance to standard plasma refinery inactivation methods and the absence of its targeted inactivation, its potential impact remains a concern.

Intravenous Bacille Calmette–Guérin vaccination protects simian immunodeficiency virus-infected macaques from tuberculosis

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is the most common cause of death in people living with human immunodeficiency virus (HIV). Intra-dermal Bacille Calmette–Guérin (BCG) delivery is the only licensed vaccine against tuberculosis; however, it offers little protection from pulmonary tuberculosis in adults and is contraindicated in people living with HIV. Intravenous BCG confers protection against Mtb infection in rhesus macaques; we hypothesized that it might prevent tuberculosis in simian immunodeficiency virus (SIV)-infected macaques, a model for HIV infection. Here intravenous BCG-elicited robust airway T cell influx and elevated plasma and airway antibody titres in both SIV-infected and naive animals. Following Mtb challenge, all 7 vaccinated SIV-naive and 9 out of 12 vaccinated SIV-infected animals were protected, without any culturable bacteria detected from tissues. Peripheral blood mononuclear cell responses post-challenge indicated early clearance of Mtb in vaccinated animals, regardless of SIV infection. These data support that intravenous BCG is immunogenic and efficacious in SIV-infected animals.

The role of sex hormones and ROS values in the control of andrology in male double-spurred Francolin (<i>Francolinus bicalcaratus</i>)

Background: This study explored the relationship between andrology, seasonal sex hormone fluctuations, and ROS values in adult male Francolinus bicalcaratus while establishing baseline parameters.
 Methods: Double-spurred Francolins (n=5 per season) were randomly selected in both dry and rainy seasons from their natural habitat. They were carefully stabilized with dewormer, antibiotics, and multivitamins, then acclimatized for two weeks at the Experimental Animal House, University of Ibadan, Nigeria. The birds were weighed, sedated, and 3 to 5 ml of blood was collected from the jugular vein in lithium heparinized bottles for serum sex hormone analysis. Testes were excised, weighed, washed with a 1.15% KCL solution, and processed for complete andrology and oxidative stress assays.
 Results: Sperm count, activity, and morphological characteristics peaked during late rainy seasons, coinciding with increased mating and hatchability. This correlated with high serum testosterone and low ROS titres in the testes. Conversely, early dry seasons witnessed declines in serum testosterone, sperm parameters, and hatchability due to increased ROS titres from food scarcity. Late dry seasons saw further declines in sex hormone levels and elevated ROS titres, leading to the absence of sperm cells.
 Conclusion: This study highlights how sex hormone and ROS titres influence sperm cell viability in double-spurred Francolins, with significant seasonal variations. These factors mainly support spermatogenesis and fertility during the breeding season, characterized by food abundance and cover. Dry season sex hormone values serve as baselines, while wet season sperm count and ROS levels represent baseline data for this bird species.

SAT462 TSI Versus TRAb In The Diagnosis Of Grave’s Disease

Abstract Disclosure: K. Ibrahim: None. K. Raju: None. M. Morkos: None. Objective: Improvement in the thyroid antibody titers can help in predicting the remission of Graves’ disease. We aimed to assess the level of elevation of the antibody titers, thyroid stimulating immunoglobulin (TSI) and thyroid receptor antibody (TRAb) in patients with Grave’s disease. Research and Design Methods: This is a retrospective cross-sectional study of patients diagnosed with Graves’ disease at an academic outpatient endocrinology clinic from August 2019 to November 2022. TSI and TRAb were measured synchronously during the initial assessment of the patients, titers were compared against the upper limit of normal to assess their level of elevation. TSI was measured using Semi-Quantitative Chemiluminescent Immunoassay and TRAb using Quantitative Electrochemiluminescent Immunoassay. SPSS® (version 28) was used for statistical analysis, descriptive statistics were utilized and paired-sample t-test was used to compare TSI And TRAb ratios. Results: We identified 41 patients who presented for initial assessment of Graves’ disease, 31 (75.6%) were female, 23 (56.1%) Caucasian, and 16 (39.0%) African American. Mean age (± standard deviation) 46.3 ± 14.2 years. Mean TSI 8.3 ± 15.9 IU/L (ref <0.55), TSI ratio of elevation above the upper limit of normal was 11.1 ± 15.3, Mean TRAb 8.9 ± 9.4 (ref ≤1.75), TRAb ratio of elevation above the upper limit of normal was 5.1 ± 5.4. The correlation coefficient for both TSI and TRAb ratios was 0.92 (p <0.001). One patient had a normal TSI but elevated TRAb level and two patients had a normal TRAb level but elevated TSI levels. Conclusion: TSI was more highly elevated above its normal range than TRAb. TSI can be a reasonable initial antibody test for patients with Graves’ disease to establish a baseline. Presentation: Saturday, June 17, 2023

SAT154 Insulin Autoimmune Syndrome In The Setting Of Metastatic Colon Cancer: Case Report

Abstract Disclosure: M. Bernal: None. J. Suarez: None. K.M. Tuna: None. F. Amer: None. M. Lamas: None. Insulin Autoinmune Syndrome is a rare cause of hypoglycemia. Its incidence is higher among Asians, Japanese patients. Also known as Hirata’s disease, it is characterized by the presence of a hyperinsulinemic state, hypoglycemia, elevated insulin antibodies titers without prior exposure to exogenous insulin, and no pathological abnormalities of the pancreatic islets cells. Some commonly used drugs and viruses have been identified as triggers. We present the case of 65-year-old male Caucasian patient who presented with recurrent episodes of hypoglycemia, that started after surgical resection of a metastatic liver lesion, in the context of metastatic colon cancer. During the workup, it was confirmed that patient had hyperinsulinemia, hypoglycemia, and positive auto-insulin antibodies without previous exposure to exogenous insulin and no imaging findings suggestive of a pancreatic abnormality. The relevance of this case is not only related to the rarity of this entity in the Western World, but also the possibility of being associated with a paraneoplastic syndrome in the setting of metastatic colon cancer, which to the best our knowledge, has not yet been described in the literature as a possible trigger of Insulin Autoimmune Syndrome. Presentation: Saturday, June 17, 2023

OC 76.4 Elevation of Antiphospholipid Antibody Titers Following Vaccination with SARS-CoV-2 mRNA in Patients with Antiphospholipid Syndrome and/or Systemic Lupus Erythematosus

OC 76.4 Elevation of Antiphospholipid Antibody Titers Following Vaccination with SARS-CoV-2 mRNA in Patients with Antiphospholipid Syndrome and/or Systemic Lupus Erythematosus

Adeno-associated virus serotype 9 antibody seroprevalence for patients in the United States with spinal muscular atrophy

Onasemnogene abeparvovec is a recombinant adeno-associated virus serotype 9 (AAV9) vector-based gene therapy for spinal muscular atrophy (SMA). Patients with elevated titers of anti-AAV9 antibodies (AAV9-Ab) should not receive onasemnogene abeparvovec because of potential safety and efficacy implications. We conducted a retrospective study to describe the seroprevalence of anti-AAV9 binding antibodies for pediatric patients with SMA in the United States. At initial testing, 13.0% (115 of 882) of patients (mean [SD] age, 26.29 [33.66] weeks) had elevated AAV9-Ab titers. The prevalence of elevated titers decreased as age increased, with 18.2% (92 of 507) of patients ≤3months old but only 1.1% (1 of 92) of patients≥21months old having elevated titers. This suggests transplacental maternal transfer of antibodies. No patterns of geographic variations in AAV9-Ab prevalence were confirmed. Elevated AAV9-Ab titers in children <6weeks old decreased in all circumstances. Lower magnitudes of elevated titers declined more rapidly than greater magnitudes. Retesting was completed at the discretion of the treating clinician, so age at testing and time between tests varied. AAV9-Ab retesting should be considered when patients have elevated titers, and elevations at a young age are not a deterrent to eventual onasemnogene abeparvovec administration. Early disease-modifying treatment for SMA leads to optimal outcomes.

Evaluation of the Effect of Tonsillectomy on Antistreptolysin O (ASO) Titer

Background: Acute recurrent tonsillitis is a common problem worldwide and tonsillectomy is the preferable treatment for patients not responding to medical treatment. Many patients with acute recurrent tonsillitis and increased antistreptolysin O (ASO) titers are caused by group A beta hemolytic streptococcal (GABHS) tonsillitis, which can lead to serious side effects such rheumatic fever and glomerulonephritis. ‎&#x0D; Aim: To assess the consequence of tonsillectomy on ASO titer.&#x0D; Patients and Method: This prospective study was conducted to analyze the consequence of tonsillectomy on 43 patients with raised antistreptolysin O (ASO) titer out of 220 patients with acute recurrent tonsillitis, for the period from October 2015 to October 2016 at Otolaryngology department, Tertiary referring hospital at Erbil, Kurdistan/Iraq. Their Demographic characteristics, medical, drug and family history and disease extent were analyzed. Postoperative follow up were processed.&#x0D; Results: The study included 43 patients between 3 to 16 years suffering from acute recurrent tonsillitis, elevated ASO titer (≥200 IU/ml) and positive throat swab for GABHS were included in the study. Six months postoperatively had been shown that there is a significant reduction in ASO titer in comparison to preoperative measures (p &lt; 0.001) and this is also applicable to the number of sore throat episodes.&#x0D; Conclusion: The main conclusion from this study is significant effect of tonsillectomy on decreasing ASO titer which reveals the reduction in postoperative GABHS throat infection, this supported by reduction of postoperative sore throat episodes.

Surveillance and treatment of primary hepatocellular carcinoma (aka. STOP HCC): protocol for a prospective cohort study of high-risk patients for HCC using GALAD-score

BackgroundVietnam and Saudi Arabia have high disease burden of primary hepatocellular carcinoma (HCC). Early detection in asymptomatic patients at risk for HCC is a strategy to improve survival outcomes in HCC management. GALAD score, a serum-based panel, has demonstrated promising clinical utility in HCC management. However, in order to ascertain its potential role in the surveillance of the early detection of HCC, GALAD needs to be validated prospectively for clinical surveillance of HCC (i.e., phase IV biomarker validation study). Thus, we propose to conduct a phase IV biomarker validation study to prospectively survey a cohort of patients with advanced fibrosis or compensated cirrhosis, irrespective of etiologies, using semi-annual abdominal ultrasound and GALAD score for five years.MethodsWe plan to recruit a cohort of 1,600 patients, male or female, with advanced fibrosis or cirrhosis (i.e., F3 or F4) and MELD ≤ 15, in Vietnam and Saudi Arabia (n = 800 each). Individuals with a liver mass ≥ 1 cm in diameter, elevated alpha-fetoprotein (AFP) (≥ 9 ng/mL), and/or elevated GALAD score (≥ -0.63) will be scanned with dynamic contrast-enhanced magnetic resonance imaging (MRI), and a diagnosis of HCC will be made by Liver Imaging Reporting and Data System (LiRADS) assessment (LiRADS-5). Additionally, those who do not exhibit abnormal imaging findings, elevated AFP titer, and/or elevated GALAD score will obtain a dynamic contrast-enhanced MRI annually for five years to assess for HCC. Only MRI nearest to the time of GALAD score measurement, ultrasound and/or AFP evaluation will be included in the diagnostic validation analysis. MRI will be replaced with an abdominal computed tomography scan when MRI results are poor due to patient conditions such as movement etc. Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced MRI will not be carried out in study sites in both countries. Bootstrap resampling technique will be used to account for repeated measures to estimate standard errors and confidence intervals. Additionally, we will use the Cox proportional hazards regression model with covariates tailored to the hypothesis under investigation for time-to-HCC data as predicted by time-varying biomarker data.DiscussionThe present work will evaluate the performance of GALAD score in early detection of liver cancer. Furthermore, by leveraging the prospective cohort, we will establish a biorepository of longitudinally collected biospecimens from patients with advanced fibrosis or cirrhosis to be used as a reference set for future research in early detection of HCC in the two countries.Trial registrationName of the registry: ClinicalTrials.govRegistration date: 22 April 2022Trial registration number: NCT05342350URL of trial registry record

Flight and flight energy accumulation related to the daily rhythm of juvenile hormone titer in the wing‐dimorphic cricket Velarifictorus aspersus

AbstractThe cricket Velarifictorus aspersus (Walker) (Orthoptera: Gryllidae) exhibits a wing dimorphism mediating two distinct life‐history strategies during early adulthood; long‐winged (LW) females mainly invest resources in flight, whereas short‐winged (SW) females invest more heavily in reproduction than LW females. To understand the relationships among juvenile hormone (JH), flight capacity, and energy accumulation, the daily rhythm of JH titer and flight activity, the concentrations of flight energy substances, and the influence of exogenous JH on flight activity and flight energy substances were investigated in V. aspersus. The results showed that the hemolymph JH titer exhibited a high‐amplitude daily rhythm in 5‐day‐old LW V. aspersus females, and the JH titer rose about 10× at 18:00 hours (6 h before lights off) and dropped to baseline levels after lights off. The females flew inactively (i.e., they floated in the air) from 14:00 to 19:00 hours during the light period, whereas they had a stronger flight capacity in the initial photophase and before lights out. The flight ability of LW females with 20 μg μL−1 JH treatments was significantly improved during periods of flight inactivity. After the peak JH titer, the concentrations of glycogen and trehalose in the flight muscles increased significantly. The LW females treated with JH during the inactive flight period had a significant increase in glycogen after 1 h and trehalose after 3 h. These results suggested that the high‐amplitude daily rhythm of the JH titer was correlated with accumulation of flight energy substance and flight capacity; that is, an elevated JH titer promoted the biosynthesis of flight energy substances, resulting in improvement of flight capacity.

Immunological Impact of Fermented Soybean Condiments Produced from Indigenous Fermenters

Several studies have shown that most condiments consumed in Nigeria today are fortified with chemicals that alter the nature and stripped the natural immunological adjuvants designed by nature to protect the body system. Several condiments have been developed from fermented foods in order to control this ugly situation but there is still controversial thought in the choice of microorganism to be used in order to produce a non-toxic condiment with an improved immunological function. The aim of this study was to evaluate the toxicity, nutritive value and immunological impact of fermented soybean condiments. Soybean (Glycine max) sample was fermented with indigenous microorganisms isolated from 7 days old fermented soybean sample; this was oven-dried, pulverized and packaged in a cleaned sterile screw capped container. The immunological impact, pro-inflammatory and anti-inflammatory activities were determined using in vivo and instrumentation techniques. Lactobacillus plantarum strain ZS 2058 (L), Bacillus subtilis strain 168 (B) and Saccharomyces cerevisiae strain YJM555 (Y) were the indigenous microbes used both singly and in consortium for the production of light to dark brown condiments with water activity ranging from 0.27 – 0.37 for the fermented soybean in the plate and 0.22 - 0.36 for the fermented soybean wrapped with Thaumatococcus danielli leaves (called Uma in Igbo and Ewe eran in Yoruba). There was pronounced delay type hypersensitivity (DTH) and significant (P&lt;0.05) elevation of lymphocyte population, rosette counts, antibody titers, phagocytic indices, total lymphocytes and malondialdehyde (MDA) values, of which pronounced activities were mostly seen on those condiments prepared with consortium of the organisms (BLY). Therefore condiments produced from fermentation of soybean using indigenous B, L, Y, BL and BLY are recommended as this would enhance its immunological impact and also safe, and those fermented in plastic plates using BLY were most efficient, preferable and acceptable.

Detection of immune effects of the Mannheimia haemolytica gamma irradiated vaccine in sheep.

Exposure to gamma rays from cobalt 60 (Co60) can induce a complete inactivation of Mannheimia haemolytica. The inactivated bacterial pathogen is a potential vaccine candidate for immunization of ruminants such as sheep. The subcutaneous administration of irradiated vaccine in a two-dose regimen (4.0 × 109 colony forming unit (CFU) per dose) results in no mortality in any of the vaccinated sheep during immunization and after subsequent challenge of the live bacteria of the same strain of M. haemolytica. A significant rise in serum IgG titer, detected through ELISA, is observed after the passage of two weeks from the inoculation of the first dose whereas, the peak of the mean serum antibody titer occurred after two weeks of booster dose. The vaccination does not bring significant change to the IFN-γ levels in serum. The bacterial challenge of the vaccinated sheep does not induce a further seroconversion relative to serum antibody titer. In conclusion, the vaccinated sheep are protected by the elevated IgG titer and increased levels of IL-4 (Th-2 response) compared to the non-vaccinated sheep. Radiation technology can provide the opportunity for mass production of immunologically safe vaccines against animal and zoonotic diseases. Ethics Approval by the National Research Center Ethics Committee (Trial Registration Number (TRN) no 13,602,023, 13/5/2023) was obtained.

Subacute sclerosing panencephalitis (SSPE): Late onset of measles complication - Case of IVIG treatment failure

Subacute sclerosing panencephalitis (SSPE) is characterized by gradual deterioration of cognitive motor and cognitive functions. SSPE more often occurs in individuals who had a history of measles viral infection. We present a case of 8 year old male child who was presented with generalized progressive weakness, recurrent falls to one side, multiple episodes of seizure, urinary incontinence. On liaison it was understood that he had a history of measles at the age of 3 years. Examination showed elevated serum measles antibody titer, electro-encephalogram (EEG) analysis revealed stereotyped polymorphic discharge seen periodically, suggestive of SSPE. He was treated with IVIG and other symptomatic treatment. However he had recurrent episodes of vomiting after IVIG administration, Ribavirin administration caused multiple oral lesions. Upon discharge he was given Syr. Valproate, Oral Steroid (Prednisolone) tapering therapy, THP 2 mg BD, PPI and Laxatives. Parents were advised to maintain RT feed of 150 mL, once in 3 hours. After 1 week, he succumbed to his illness at his residence.

Insertion of an immunodominant T helper cell epitope within the Group A Streptococcus M protein promotes an IFN-γ-dependent shift from a non-protective to a protective immune response.

The common pathogen Group A Streptococcus (GAS, Streptococcus pyogenes) is an extracellular bacterium that is associated with a multitude of infectious syndromes spanning a wide range of severity. The surface-exposed M protein is a major GAS virulence factor that is also target for protective antibody responses. In this study, we use a murine immunization model to investigate aspects of the cellular and molecular foundation for protective adaptive immune responses generated against GAS. We show that a wild type M1 GAS strain induces a non-protective antibody response, while an isogenic strain carrying the immunodominant 2W T helper cell epitope within the M protein elicits an immune response that is protective against the parental non-recombinant M1 GAS strain. Although the two strains induce total anti-GAS IgG levels of similar magnitude, only the 2W-carrying strain promotes elevated titers of the complement-fixing IgG2c subclass. Protection is dependent on IFN-γ, and IFN-γ-deficient mice show a specific reduction in IgG2c levels. Our findings suggest that inclusion of the 2W T cell epitope in the M protein confers essential qualitative alterations in the adaptive immune response against GAS, and that sparsity in IFN-γ-promoting Th cell epitopes in the M protein may constitute an immune evasion mechanism, evolved to allow the pathogen to avoid attack by complement-fixing antibodies.

MiR34a-5p impedes CLOCK expression in chronodisruptive C57BL/6J mice and potentiates pro-atherogenic manifestations.

Altered circadian rhythms underlie manifestation of several cardiovascular disorders, however a little is known about the mediating biomolecules. Multiple transcriptional-translational feedback loops control circadian-clockwork wherein; micro RNAs (miRNAs) are known to manifest post transcriptional regulation. This study assesses miR34a-5p as a mediating biomolecule. 8-10-week-old male C57BL/6J mice (n = 6/group) were subjected to photoperiodic manipulation induced chronodisruption and thoracic aortae were examined for miRNA, gene (qPCR) and protein (Immunoblot) expression studies. Histomorphological changes were assessed for pro-atherogenic manifestations (fibrillar arrangement, collagen/elastin ratio, intima-media thickening). Computational studies for miRNA-mRNA target prediction were done using TargetScan and miRDB. Correlative in vitro studies were done in serum synchronized HUVEC cells. Time point based studies were done at five time points (ZT 0, 6, 12, 18, 24) in 24h. Chronodisruption induced hypomethylation in the promoter region of miR34a-5p, in the thoracic aortae, culminating in elevated miRNA titers. In a software-based detection of circadian-clock-associated targets of miR34a-5p, Clock and Sirt1 genes were identified. Moreover, miR34a-5p exhibited antagonist circadian oscillations to that of its target genes CLOCK and SIRT1 in endothelial cells. Luciferase reporter gene assay further showed that miR34a-5p interacts with the 3'UTR of the Clock gene to lower its expression, disturbing the operation of positive arm of circadian clock system. Elevated miR34a-5p and impeded SIRT1 expression in a chronodisruptive aortae exhibited pro-atherogenic changes observed in form of gene expression, increased collagen/elastin ratio, fibrillar derangement and intimal-media thickening. The study reports for the first time chronodisruption mediated miR34a-5p elevation, its circadian expression and interaction with the 3'UTR of Clock gene to impede its expression. Moreover, elevated miR34a-5p and lowered SIRT1 expression in the chronodisruptive aortae lead off cause-consequence relationship of chronodisruption mediated proatherogenic changes.

Changes of allergic inflammation and immunological parameters after Alt a 1 and A. alternata immunotherapy in mice

BackgroundThe efficacy of allergen-specific subcutaneousimmunotherapy (SCIT) with Alt a 1 of the fungus A. alternata is still unknown. Yet, few studies compare the therapeutic effects and immunological mechanisms of Alt a 1 and A. alternata extracts. We aim to explore and compare the changes in allergic inflammation and immunological mechanisms of Alt a 1 and A. alternata in mice. MethodsFemale BALB/c mice administrated recombinant Alt a 1 (rAlt a 1), native Alt a 1 (nAlt a 1), and A. alternata. Lung histology, airway hyper-reactivity (AHR), bronchoalveolar lavage fluid (BALF) cytokine levels, serum immunoglobulin responses, the expression of Bcl-6, the percentages of T follicular helper cells (Tfh), cytokine-related Tfh subtypes, regulatory B cells (Breg), and IL-10+ Breg cells were detected. ResultsHigh-purity nAlt 1 protein was obtained. SCIT with Alt a 1 and Alternaria decreased airway and lung inflammation, including improvement of lung pathology, lower levels of AHR, reduction of total cell numbers, and IL-4 and IL-13 levels in BALF. Furthermore, Alt a 1-SCIT effectively suppressed the IgE responses, elevated IgG titers, and was superior in decreasing the expression of Bcl-6. Additionally, Alternaria-SCIT significantly decreased the expression of Tfh cells, L-4+ Tfh, and IL-5+ Tfh cells in the spleen, whereas Alt a 1 showed superior therapeutic effects in the lymph node. IL-13+ Tfh cells in these two treatment groups not being significant. IL-17A+ Tfh cells were alleviated most effectively after A. alternata-SCIT in both the spleen and lymph node. Intriguingly, IL-10+ Breg cells decreased remarkably in response to SCIT with rAlt a 1. ConclusionsTreatments with Alt a 1 and A. alternata extracts had beneficial effects on allergic inflammation. Alt a 1-SCIT resulted in prominent improvement in the immunoglobulin responses, Bcl-6, and IL-10+ Breg cells. Alternaria-SCIT was more likely to suppress the expression of Tfh and cytokine-related Tfh subtypes.

Serologic Testing for Rocky Mountain Spotted Fever in a Low-Incidence Region.

Tick-borne diseases have grown in incidence over recent decades. As a result, diagnostic testing has become more common, often performed as broad antibody-based panels for multiple tick-transmitted pathogens. Rocky Mountain spotted fever (RMSF) is rare in our region yet may cause severe morbidity, leading to diagnostic screening in low-risk patients. We sought to describe trends in RMSF diagnostic testing, rate of IgG seropositivity, and clinical features of those tested. We performed a retrospective chart review of patients ≤21 years old undergoing testing for RMSF and/or with an ICD-9/10 code for RMSF. Patients were categorized by infection likelihood based on clinical and laboratory criteria adapted from Centers for Disease Control and Prevention's (CDC) case definition of spotted fever rickettsioses. Clinical data were collected and analyzed with descriptive statistics. One hundred and seventy patients were included. 5.8% met CDC criteria for rickettsial infection, 6.5% had an elevated IgG titer but lacked suggestive symptoms, and 87.6% had a negative IgG titer. Many patients tested were unlikely to have RMSF, including 50% lacking fever, 20% lacking any RMSF "classic triad" symptoms, 13% without acute illness, and 22% tested during months with low tick activity. Convalescent serology was performed in 7.6% of patients and none underwent Rickettsia rickettsii polymerase chain reaction (PCR) testing. Diagnostic testing was frequently performed in patients unlikely to have RMSF. We identified many opportunities for improving test utilization. Reserving testing for those with higher pretest probability, performing convalescent serology, and utilizing PCR may improve the accuracy of RMSF diagnosis and reduce clinical challenges stemming from inappropriate testing.

Elevated Preoperative TPO Ab Titers Decrease Risk for DTC in a Linear Fashion: A Retrospective Analysis of 1635 Cases.

For some, chronic lymphocytic thyroiditis (Hashimoto thyroiditis) is an important risk factor for differentiated thyroid cancer (DTC). Surgical cohort studies even suggested a potential role for thyroid peroxidase antibodies (TPO-Abs) on that risk. Our clinical observations argued against that possibility. We designed the present study to evaluate the relationship of TPO-Abs and DTC in a large patient population. We recruited individuals who underwent thyroidectomies at 4 different clinical sites (USA: 1 clinic, 2000-2013, and Greece: 3 clinics, 2007-2021). We gathered data on TPO-Abs titers measured with commercially available chemiluminescence immunoassays, and reviewed patients' data including surgical pathology. TPO-Abs of 34 IU/mL or greater was deemed positive (TPO+) and TPO-Abs less than 34 IU/mL was deemed negative (TPO-). Odds ratios (OR) for DTC were calculated with the Fisher exact test and P less than .05 was deemed significant. We reviewed data from 8461 consecutive thyroid surgery cases. TPO-Abs titers were available for 1635 individuals: DTC n = 716 (43.8%), benign pathology n = 919 (56.2%), TPO+ n = 540 (33.0%), and TPO- n = 1095 (67.0%). DTC was found at a lower frequency in TPO+ (198/540, 36.7%) compared to TPO- (518/1095, 47.3%) patients, OR 0.64 (0.52-0.80; P < .0001). Rising TPO-Abs titers conferred protection against DTC in a linear fashion: TPO-Abs less than 10 IU/mL: 59.3%, TPO-Abs less than 34 IU/mL: 47.4%, TPO-Abs 34 to 100 IU/mL: 42.6%, TPO-Abs 100 to 500 IU/mL: 32.0%, TPO-Abs greater than 1000 IU/mL: 19.4%; P less than .0001. Higher TPO-Ab titers appear protective against DTC in our large multicenter cohort of patients who underwent thyroidectomies. Rising preoperative TPO-Abs titers conferred linearly increasing protection against DTC.

Co-circulation and co-infection of hantaviruses and Wenzhou mammarenavirus in small mammals and humans in Jiangxi, China.

Both Orthohantaviruses (HV) and Whenzhou Mammarenaviruses (WENV) are rodents borne viruses, allowing them to spread simultaneously in the same area and infect humans. To explore the potential threat of HV and WENV to public health safety, an environmental and laboratory investigation was conducted in 2020-2021, in Jiangxi province, China. A total of 461 small mammals of 7 species and paired sera from 43 suspected HFRS cases were collected from Jiangxi Province, China. Viral genomic RNA and specific antibodies against HV and WENV were detected to evaluate the epidemic situation of the two viruses. Hantaan virus (HTNV), seoul virus (SEOV) and WENV RNA were detected in the lungs of the captured mammals, which resulted 4.1% and 7.4% of HV and WENV RNA positive respectively. Co-infections of WENV and SEOV were detected from Rattus norvegicus, Mus musculus and Rattus flavipectus with an overall co-infection rate of 0.65%. The detection rates of antibodies in the blood against HV and WENV were 11.9% (55/461), and 13.2% (61/461) respectively. The prevalence of viral infection and viral genetic characters varied among the selected areas. In the paired sera of 43 suspected HFRS cases, 38 were with HV infection, 11 were with WENV IgG, and 7 with a 4-fold or more of WENV IgG titer elevation. These results revealed the fact of the co-circulating and coinfection of HV and WENV in the same area at the same time, which might impact on public health safety.