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Frontiers in Immunology 2024Sex-based differences in immune cell composition and function can contribute to distinct adaptive immune responses. Prior work has quantified these differences in...
Sex-based differences in immune cell composition and function can contribute to distinct adaptive immune responses. Prior work has quantified these differences in peripheral blood, but little is known about sex differences within human lymphoid tissues. Here, we characterized the composition and phenotypes of adaptive immune cells from male and female ex vivo tonsils and evaluated their responses to influenza antigens using an immune organoid approach. In a pediatric cohort, female tonsils had more memory B cells compared to male tonsils direct ex vivo and after stimulation with live-attenuated but not inactivated vaccine, produced higher influenza-specific antibody responses. Sex biases were also observed in adult tonsils but were different from those measured in children. Analysis of peripheral blood immune cells from vaccinated adults also showed higher frequencies of tissue homing CD4 T cells in female participants. Together, our data demonstrate that distinct memory B and T cell profiles are present in male vs. female lymphoid tissues and peripheral blood respectively and suggest that these differences may in part explain sex biases in response to vaccines and viruses.
Topics: Humans; Female; Male; Child; Palatine Tonsil; Adult; Influenza Vaccines; Influenza, Human; Sex Characteristics; Child, Preschool; Adolescent; Antibodies, Viral; Memory B Cells; Organ Specificity; Young Adult; Sex Factors; CD4-Positive T-Lymphocytes; B-Lymphocytes; Immunologic Memory
PubMed: 38812520
DOI: 10.3389/fimmu.2024.1373537 -
EJNMMI Research May 2024F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes...
BACKGROUND
F-18-flurodeoxyglucose (FDG) PET/CT is routinely used for staging, evaluation of response to treatment and follow-up of most pediatric malignancies. Cervical lymph nodes can be involved in some pediatric malignancies, but increased uptake in non-malignant cervical lymph nodes is not exceptional in this population. The aim of the present study is to identify predictors of the maximum uptake in non-malignant cervical lymph nodes in the pediatric population.
METHODS
191 FDG PET/CT studies of pediatric patients without malignant involvement of cervical lymph nodes were retrospectively reviewed. The maximal Standard Uptake Value in the hottest cervical lymph node (SUVmax), as well as demographic, technical and imaging variables were recorded. The predictive effect of those variables on SUVmax was estimated using linear regression models.
RESULTS
Increased FDG activity in cervical nodes was observed in 136/191 studies (71%). The mean SUVmax was 2.2 ± 1.3. Ipsilateral palatine tonsil SUVmax, mean liver uptake, and treatment status were all statistically significant predictors of SUVmax. However, in multivariate regression analysis, only ipsilateral palatine tonsil SUVmax was found to be significant. In addition, SUVmax was greater than the mean liver uptake in 50% of all studies. This proportion was higher in younger children, reaching 77% of studies of children younger than six years.
CONCLUSION
SUVmax in ipsilateral palatine tonsil is a strong predictor of the maximal uptake value of non-malignant cervical lymph nodes in children. The intensity of uptake in non-malignant cervical lymph nodes is frequently higher than liver uptake in children, and this tendency increases for younger patients.
TRIAL WAS REGISTERED
In the internal hospital registry under TRN 0209-22-HMO on date 23.04.2022.
PubMed: 38809472
DOI: 10.1186/s13550-024-01110-9 -
International Journal of Pediatric... Jun 2024Sleep apnea is a prevalent issue in children, associated with significant morbidities such as cardiovascular and neurocognitive disorders. There is increasing interest...
OBJECTIVES
Sleep apnea is a prevalent issue in children, associated with significant morbidities such as cardiovascular and neurocognitive disorders. There is increasing interest in intra-capsular tonsillectomy by coblation (ICTC) as a method to address obstructive sleep apnea (OSA) in children. However, the literature remains controversial regarding the most effective intra-capsular tonsillectomy (ICT) technique with the least morbidity. Our current research extends a previous study that established the effectiveness and safety of ICTC, demonstrating rapid post-surgical recovery with minimal analgesic needs. This new investigation specifically focuses on long-term follow-up. Our aim is to assess tonsil regrowth and the risk of recurrence of OSA symptoms at a mean follow-up of 6.1 years post-surgery. By presenting the results of this extended study, our goal is to gain a better understanding of the long-term effectiveness of this surgical intervention in treating OSA in children. Thus, considering the initial benefits, we will also explore potential long-term implications.
MATERIALS AND METHODS
This research follows up on children from our previous study who underwent ICTC, with or without adenoidectomy, for OSA resulting from tonsillar hypertrophy at a tertiary-level university hospital between March 2016 and March 2018. They were followed up for an average of 6.1 years postoperatively. Symptom recurrence is assessed by comparing preoperative OSA-18 questionnaire results with those obtained at the 6.1-year mark. Tonsil regrowth is evaluated by comparing preoperative Brodsky scores with those obtained at 6.1 years.
RESULTS
The mean total score of OSA-18 significantly decreased from 79.41 (SD = 14.95) before ICTC to 25.47 (SD = 8.92) at 6.1 years postoperatively (p < 0.001, mean difference = 53.94, 95 % CI [50.32, 57.56]). Similarly, the mean Brodsky score dropped from 2.95 (SD = 0.51) before ICTC to 1.04 (SD = 0.24) 6.1 years postoperatively (p < 0.001, mean difference = 1.92, 95 % CI [1.80, 2.04]). The overall regrowth rate was 2.35 % (n = 2), with a revision surgery rate of 1.18 % (n = 1).
CONCLUSION
ICTC exhibits minimal risk of tonsil regrowth and maintains long-term efficacy in preventing the recurrence of OSA symptoms. Therefore, it justifies broader utilization in addressing OSA symptoms arising from tonsillar hypertrophy in children.
Topics: Humans; Tonsillectomy; Female; Male; Child; Recurrence; Sleep Apnea, Obstructive; Palatine Tonsil; Child, Preschool; Treatment Outcome; Follow-Up Studies; Hypertrophy
PubMed: 38805935
DOI: 10.1016/j.ijporl.2024.111992 -
International Journal of Molecular... May 2024Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying...
Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.
Topics: Humans; Glomerulonephritis, IGA; Tonsillectomy; Palatine Tonsil; Female; Male; Adult; Kidney Glomerulus; Retrospective Studies; Middle Aged; Tonsillitis; Young Adult; Immunoglobulin A
PubMed: 38791337
DOI: 10.3390/ijms25105298 -
Veterinary Journal (London, England :... Jun 2024The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in...
The pharyngeal tonsil, located in the nasopharynx, can effectively defend against pathogens invading the body from the upper respiratory tract and play a crucial role in mucosal immunity of the respiratory tract. Immunoglobulin A (IgA) and Immunoglobulin G (IgG) serve as key effector molecules in mucosal immunity, exhibiting multiple immune functions. This study aimed to investigate the distribution patterns and age-related alterations of IgA and IgG antibody-secreting cells (ASCs) in the pharyngeal tonsils of Bactrian camels. Twelve Alashan Bactrian camels were categorized into four age groups: young (1-2 years, n=3), pubertal (3-5 years, n=3), middle-aged (6-16 years, n=3) and old (17-20 years, n=3). The distribution patterns of IgA and IgG ASCs in the pharyngeal tonsils of Bactrian camels of different ages were meticulously observed, analyzed and compared using immunohistochemical and statistical methods. The results revealed that IgA ASCs in the pharyngeal tonsils of all age groups were primarily clustered or diffusely distributed in the reticular epithelium and its subepithelial regions (region A) and around the glands (region C), scattered in the subepithelial regions of non-reticular epithelium (region B), and sporadically distributed in the interfollicular regions (region D). Interestingly, the distribution pattern of IgG ASCs in the pharyngeal tonsils closely mirrored that of IgA ASCs. The distribution densities of IgA and IgG ASCs in these four regions were significantly decreased in turn (P<0.05). However, IgA ASCs exhibited significantly higher densities than IgG ASCs in the same region (P<0.05). Age-related alterations indicated that the distribution densities of IgA and IgG ASCs in each region of the pharyngeal tonsils exhibited a trend of initially increasing and subsequently decreasing from young to old camels, reaching a peak in the pubertal group. As camels age, there was a significant decrease in the densities of IgA and IgG ASCs in all regions of the pharyngeal tonsils (P<0.05). The results demonstrate that the reticular epithelium and its subepithelial regions in the pharyngeal tonsils of Bactrian camels are the primary regions where IgA and IgG ASCs colonize and exert their immune functions. These regions play a pivotal role in inducing immune responses and defending against pathogen invasions in the pharyngeal tonsils. IgA ASCs may be the principal effector cells of the mucosal immune response in the pharyngeal tonsils of Bactrian camels. Aging significantly reduces the densities of IgA and IgG ASCs, while leaving their distribution patterns unaffected. These findings will provide valuable insights for further investigations into the immunomorphology, immunosenescence, and response mechanisms of the pharyngeal tonsils in Bactrian camels.
Topics: Animals; Camelus; Immunoglobulin G; Immunoglobulin A; Antibody-Producing Cells; Aging; Age Factors; Male; Immunity, Mucosal; Adenoids; Female; Palatine Tonsil
PubMed: 38763403
DOI: 10.1016/j.tvjl.2024.106131 -
PloS One 2024Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for...
BACKGROUND
Altered immunological responses in the palatine tonsils may be involved in the pathogenesis of IgA nephropathy (IgAN). The germinal center serves as the site for antigen-specific humoral immune responses in the palatine tonsils. Germinal center involution is frequently observed in the palatine tonsils of IgAN (IgAN tonsils). However, the pathogenic significance of these characteristic changes remains unclear. This study aimed to investigate the morphological changes in secondary lymphoid follicles in IgAN tonsils and to evaluate the correlation between the morphometric results and the clinicopathological severity of IgAN.
METHODS
The tonsils of age-matched patients with recurrent tonsillitis (RT tonsils) were used as controls. The correlation between the degree of lymphoid follicular involution and histopathological severities in clinical or kidney biopsy was evaluated.
RESULTS
In total, 87 patients with IgAN were included (48% male, median age 35 years, median estimated glomerular filtration rate: 74 mL/min/1.73 m2). Compared to RT tonsils, IgAN tonsils showed smaller median sizes of lymphoid follicles and germinal centers (P < 0.001). The relative areas of lymphoid follicles (%LFA) and germinal centers (%GCA) in the total tonsillar tissue were smaller in the IgAN tonsils than in the RT tonsils (P < 0.001). In contrast, the median proportion of mantle zones in the total tonsillar tissue was comparable between the groups. A lower %LFA was associated with a longer period from the onset of urinary abnormalities to biopsy diagnosis and higher urinary protein excretion (P = 0.01). %LFA showed significant negative correlations with frequencies of glomeruli with both global and segmental sclerosis.
CONCLUSIONS
The present study confirmed accelerated germinal center involution in the tonsils of patients with IgAN. This characteristic change in the IgAN tonsil correlates with heavy proteinuria and advanced chronic histopathological changes in the kidneys, thereby suggesting the involvement of repeated tonsillar immunoreactions during IgAN progression.
Topics: Humans; Glomerulonephritis, IGA; Palatine Tonsil; Germinal Center; Male; Female; Adult; Tonsillitis; Middle Aged; Young Adult; Kidney
PubMed: 38709804
DOI: 10.1371/journal.pone.0301853 -
Fujita Medical Journal May 2024To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea-hypopnea index (AHI) and to determine...
OBJECTIVE
To determine whether the combination of the pharyngeal tonsil grade and palatine tonsil grade results in differences in the apnea-hypopnea index (AHI) and to determine whether each parameter separately (pharyngeal tonsil grade and palatine tonsil grade) results in differences in severe obstructive sleep apnea (OSA).
METHODS
This cross-sectional study involved 107 children (mean age, 7.2 years; range, 4-12 years) suspected of having OSA because of snoring or sleep-related complaints. The patients underwent polysomnography, and their palatine and pharyngeal tonsils were graded.
RESULTS
In examining whether the palatine tonsils and pharyngeal tonsils could be risk factors for severe OSA, the adjusted odds ratios were 4.42 for palatine tonsil grade 4 versus 1-3 and 10.40 for pharyngeal tonsil grade 4 versus 1-3; both were highly statistically significant. We also found that the AHI when both the pharyngeal and palatine tonsils were grade 4 was higher than the AHI expected for the pharyngeal and palatine tonsils alone.
CONCLUSIONS
The combination of grade 4 pharyngeal tonsils and grade 4 palatine tonsils resulted in an AHI much higher than the AHI of other combinations (pharyngeal tonsils grades 1-3 and 4, palatine tonsils grades 1-3 and 4). We believe that grade 4 pharyngeal tonsils and grade 4 palatine tonsils have a great influence on severe OSA and that grade 4 pharyngeal tonsils increase the AHI.
PubMed: 38708074
DOI: 10.20407/fmj.2023-011 -
American Journal of Otolaryngology 2024TORS is a minimally invasive surgical alternative to chemoradiotherapy for oropharyngeal malignancies. While early postoperative oropharyngeal dysphagia is linked to...
OBJECTIVE
TORS is a minimally invasive surgical alternative to chemoradiotherapy for oropharyngeal malignancies. While early postoperative oropharyngeal dysphagia is linked to TORS, this study explores both subjective and objective swallowing outcomes.
STUDY DESIGN
Retrospective and prospective review of the patients who underwent TORS for oropharyngeal malignancy from 2018 to 2023.
SETTING
Single tertiary referral center.
METHODS
Postoperative transnasal feeding tubes were administered to 142 patients undergoing TORS. Data on oncological, clinical, surgical, and pathological parameters, including VFSS records, pain with swallow, and feeding tube removal timing, were collected. Clinical swallow exam (CSE) was conducted on POD-1, with a formal swallow study pursued if inconclusive. Once a safe swallow was confirmed, oral diets were initiated, and the feeding tube removed, with most patients discharged on POD-2.
RESULTS
At an average age of 59.3 years on the day of operation, the palatine tonsil (N = 101) was the predominant subsite. A dobhoff feeding tube was intraoperatively placed in 98 % of patients (N = 139). On POD-1, CSE was conducted in 119 patients, with 26 % (37/119) cleared for total oral diet (NOMS ≥ 4). Additionally, 30 out of 73 VFSS patients were cleared for total oral diet. A total of 54.9 % (78/142) had the feeding tube removed before discharge on POD-2, with a mean time of 6.5 ± 6.6 days. Overall, 71.1 % (101/142) achieved a total oral diet within one week after TORS.
CONCLUSION
Early post-TORS swallowing is vital for oropharyngeal malignancies. VFSS assesses post-operative swallowing safety, allowing most patients to resume total oral nutrition shortly after TORS.
Topics: Humans; Oropharyngeal Neoplasms; Middle Aged; Male; Female; Deglutition Disorders; Retrospective Studies; Prospective Studies; Aged; Deglutition; Fluoroscopy; Enteral Nutrition; Postoperative Complications; Minimally Invasive Surgical Procedures; Video Recording; Adult
PubMed: 38704947
DOI: 10.1016/j.amjoto.2024.104336 -
Analytical Chemistry May 2024Single-cell spatial proteomic analysis holds great promise to advance our understanding of the composition, organization, interaction, and function of the various cell...
Single-cell spatial proteomic analysis holds great promise to advance our understanding of the composition, organization, interaction, and function of the various cell types in complex biological systems. However, the current multiplexed protein imaging technologies suffer from low detection sensitivity, limited multiplexing capacity, or are technically demanding. To tackle these issues, here, we report the development of a highly sensitive and multiplexed in situ protein profiling method using off-the-shelf antibodies. In this approach, the protein targets are stained with horseradish peroxidase (HRP) conjugated antibodies and cleavable fluorophores via click chemistry. Through repeated cycles of target staining, fluorescence imaging, and fluorophore cleavage, many proteins can be profiled in single cells in situ. Applying this approach, we successfully quantified 28 different proteins in human formalin-fixed paraffin-embedded (FFPE) tonsil tissue, which represents the highest multiplexing capacity among the tyramide signal amplification (TSA) methods. Based on their unique protein expression patterns and their microenvironment, ∼820,000 cells in the tissue are classified into distinct cell clusters. We also explored the cell-cell interactions between these varied cell clusters and observed that different subregions of the tissue are composed of cells from specific clusters.
Topics: Humans; Fluorescent Dyes; Click Chemistry; Palatine Tonsil; Single-Cell Analysis; Proteins; Proteomics; Horseradish Peroxidase; Optical Imaging; Paraffin Embedding
PubMed: 38663032
DOI: 10.1021/acs.analchem.4c01273 -
Sleep Medicine Jul 2024Most children treated for obstructive sleep disordered breathing (oSDB) are not systematically assessed by polysomnography (PSG) nor by structuredsymptom quantification...
OBJECTIVE/BACKGROUND
Most children treated for obstructive sleep disordered breathing (oSDB) are not systematically assessed by polysomnography (PSG) nor by structuredsymptom quantification before surgical treatment. The main objective of this study wasto investigate the effect of adeno-tonsillotomy (ATO) on symptom burden and PSGparameters.
METHODS
Children aged 2-10 years with oSDB were selected for ATO based uponclinical findings according to current standards of care in Denmark. Each childunderwent standardized assessment before and 3 months after surgery, including aPSG, tonsil size assessment, and the Pediatric Sleep Questionnaire -Sleep RelatedBreathing Disorder (PSQ) to quantify symptom burden. Obstructive sleep apnea (OSA)was defined as an obstructive apnea-hypopnea index (oAHI) ≥2/h. Successfultreatment was defined as post-surgery oAHI ≤5/h, and complete cure as oAHI ≤2/h.
RESULTS
Fifty-two children were included. Mean age was 5.0 years (SD ± 1.76). Thirteen children were identified with baseline oAHI <2/h. Significant improvement inOSA severity was observed in children with moderate-to-severe OSA, in whom oAHI decreased from 15.7/h to 2.6/h (p < 0.001). Treatment success was obtained in 85% and cure was obtained in 42% of children. PSQ-score significantly improved from 0.52 (CI 0.47-0.56) to 0.26 (CI 0.21-0.32) (p < 0.001). Baseline OSA severity was notcorrelated to baseline symptom burden nor to symptom relief after ATO. There were noserious adverse events.
CONCLUSIONS
Adeno-tonsillotomy significantly reduced symptom burden in otherwise healthy children with oSDB symptoms. Significant improvement in oAHI was observedonly in children with moderate-to-severe OSA. We recommend combining clinicalevaluation with PSQ and oAHI.
Topics: Humans; Male; Female; Sleep Apnea, Obstructive; Child, Preschool; Tonsillectomy; Child; Polysomnography; Treatment Outcome; Surveys and Questionnaires; Denmark; Adenoidectomy; Palatine Tonsil; Severity of Illness Index
PubMed: 38652931
DOI: 10.1016/j.sleep.2024.04.014