Dynamic regulation of B cell complement signaling is integral to germinal center responses.

Maturation of B cells within germinal centers (GCs) generates diversified B cell pools and high-affinity B cell antigen receptors (BCRs) for pathogen clearance. Increased receptor affinity is achieved by iterative cycles of T cell-dependent, affinity-based B cell positive selection and clonal expansion by mechanisms hitherto incompletely understood. Here we found that, as part of a physiologic program, GC B cells repressed expression of decay-accelerating factor (DAF/CD55) and other complement C3 convertase regulators via BCL6, but increased the expression of C5b-9 inhibitor CD59. These changes permitted C3 cleavage on GC B cell surfaces without the formation of membrane attack complex and activated C3a- and C5a-receptor signals required for positive selection. Genetic disruption of this pathway in antigen-activated B cells by conditional transgenic DAF overexpression or deletion of C3a and C5a receptors limited the activation of mechanistic target of rapamycin (mTOR) in response to BCR-CD40 signaling, causing premature GC collapse and impaired affinity maturation. These results reveal that coordinated shifts in complement regulation within the GC provide crucial signals underlying GC B cell positive selection.

Evaluation of the local and systemic pattern of sensitization to allergens in patients with adenotonsillar hypertrophy.

PURPOSE: Adenotonsillar hypertrophy (ATH) is a medical condition characterized by the enlargement or swelling of the tonsils. The role of allergy in ATH has not been persuasively evidenced. Therefore, we investigated the state of humoral immunity and the presence of specific immunoglobulin E (sIgE) in tissues and sera in children suffering from TH. METHODS: According to the skin prick test (SPT) result, 44 ATH children were divided into the atopic and non-atopic groups. The level of sIgE against 30 inhalants and food allergens in the sera and tissue homogenates was measured by a commercial allergy immunoblotting kit. In addition, we evaluated the following variables in both tonsillar tissue homogenates and serum: total IgE, IgA, IgM, IgG, and tissue eosinophil counts. RESULTS: Our results showed that 21 (47.7%) of patients with ATH were sensitized to at least one allergen in the adenotonsillar sample and/or sera. Only two patients were negative for sIgE in the atopic group, but in the non-atopic group, only one had positive sIgE results. In the atopic group, 19 (86.4%) patients had positive sIgE in tonsillar tissues, and 18 (81.8%) had sensitized serum. There were no statistical differences in the case of other antibodies except IgE levels between the two groups. The average eosinophilic count was significantly higher in atopic patients than in the non-atopic group. CONCLUSION: The results of this study support the role of allergy in the pathogenesis of ATH and confirmed local allergic inflammation in tonsillar tissue.

Causal association of gastroesophageal reflux disease with chronic sinusitis and chronic disease of the tonsils and adenoids.

BACKGROUND: Exploring bidirectional causal associations between gastroesophageal reflux disease (GERD) and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively. METHODS: We first conducted a TSMR (two-sample mendelian randomization) study using the results of the inverse variance weighting method as the primary basis and bidirectional MR to rule out reverse causation. Subsequently, MVMR (multivariate MR) analysis was performed to identify phenotypes associated with SNPs and to explore the independent effect of GERD on two outcomes. Finally, we calculated MR-Egger intercepts to assess horizontal polytropy and Cochran's Q statistic to assess heterogeneity and ensure the robustness of the study. RESULTS: For each standard deviation increase in genetically predicted GERD rate, there was an increased risk of chronic disease of the tonsils and adenoids (OR 1.162, 95% CI 1.036-1.304, P: 1.06E-02) and of developing chronic sinusitis (OR 1.365, 95% CI 1.185-1.572, P: 1.52E-05), and there was no reverse causality. Causality for TSMR was obtained on the basis of IVW (inverse variance weighting) and appeared to be reliable in almost all sensitivity analyses, whereas body mass index may be a potential mediator of causality between GERD and chronic sinusitis. CONCLUSION: There is a causal association between GERD and chronic disease of the tonsils and adenoids and chronic sinusitis, respectively, and the occurrence of GERD increases the risk of developing chronic disease of the tonsils and adenoids and chronic sinusitis.

Histological Correlation between Tonsillar and Glomerular Lesions in Patients with IgA Nephropathy Justifying Tonsillectomy: A Retrospective Cohort Study.

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.

[Disproving the myth of "abscess weather" predisposing to peritonsillitis and peritonsillar abscess]. / Widerlegung des Mythos vom "Abszesswetter", welches das Auftreten von Peritonsillitiden und Peritonsillarabszessen begünstigt.

BACKGROUND: Peritonsillar abscess (PTA) is often seen as a complication of acute tonsillitis and is defined as pus retention between the tonsillar capsule and the peritonsillar tissue. The etiology and pathogenesis have not yet been fully elucidated. A connection between certain weather conditions and temperature fluctuations and the occurrence of abscesses in the head and neck region has been discussed for years. The question here is whether higher temperature fluctuations are predisposing for the formation of abscesses. MATERIALS AND METHODS: A retrospective evaluation of all patients hospitalized with peritonsillitis or PTA in the Department of Otorhinolaryngology of the Klinikum Rechts der Isar of the Technical University of Munich during a period of 10 years (2012-2021) was performed. Each patient was individually correlated with daily temperature data from the statistical meteorological office of the City of Munich. RESULTS: A total of 1450 patients were included, 270 patients (18.62%) with peritonsillitis and 1180 patients (81.38%) with PTA. A correlation between the occurrence of peritonsillitis or PTA and major temperature fluctuations could be excluded in this large patient population. Moreover, a similar frequency of peritonsillitis and PTA was seen throughout the year. CONCLUSION: The myth of a temperature dependence of the development of peritonsillitis or PTA and a so-called abscess weather could be negated in this study.

Extranodal natural killer/T-cell lymphoma with tonsil involvement: a case report.

BACKGROUND: Extranodal natural killer/T-cell lymphoma (ENKTL) with tonsil involvement is not common, especially in children. CASE PRESENTATION: A 13-year-old girl presented with an unexplained sore throat for more than 2 months, together with intermittent fever and suppurative tonsilitis. Nasopharyngoscopy revealed a pharyngeal mass. Enhanced computed tomography (CT) scan showed tonsillar hypertrophy and punctate calcification. Chronic pyogenic granulomatous inflammation with pseudoepithelial squamous epithelial hyperplasia was observed in left tonsil, and pyogenic granulomatous inflammation and a small number of T-lymphoid cells were detected in the right tonsil. The immunohistochemical results showed CD2+, CD3+, CD4+, CD5+, CD8+, granzyme B+, and TIA-1+. The Ki-67 proliferation index was 20%. The case showed T cell receptor gene rearrangement. Finally, the case was diagnosed as ENKTL of stage II with tonsil involvement. The patient received 6 cycles of chemotherapy with SMILE regimen, and showed complete response with no recurrence in the follow-up. CONCLUSION: We presented a rare case of ENKTL with tonsil involvement in a child. The patient showed complete response to the SMILE chemotherapy with no recurrence.

Predictive values of Mallampati score, tonsillar size, and BMI z-score in the presence and severity of obstructive sleep apnea in pediatric population.

Background/aim: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder in children. Determination of risk factors for the development of OSA is essential for early diagnosis and treatment of the disease and decreases the risk of negative consequences. This study aimed to investigate the predictive values of Mallampati score, tonsillar size, and BMI z-score in the presence and severity of OSA in children. Materials and methods: This prospective cross-sectional study included 114 children with OSA symptoms. All children were assessed by BMI z-score, Mallampati score, and tonsillar size and underwent overnight polysomnography. They were consecutively selected and assigned to 4 groups as follows: Group 1 included normal-weight with a low Mallampati score; Group 2 involved normal-weight with a high Mallampati score; Group 3 included obese with a low Mallampati score; and Group 4 involved obese with a high Mallampati score. Results: Of the 114 included children, 58 were female and 56 were male, with a mean age of 13.1 ± 2.9 years. OSA frequency and apnea-hypopnea index were significantly higher in group 4 compared with other groups (p = 0.003 and p < 0.0001, respectively), whereas average and minimum spO2 were significantly lower (for both, p = 0.001). Mallampati score and BMI z-score were found to be significant for predicting OSA (odds ratio = 4.147, 95% CI: 1.440-11.944; p = 0.008 and odds ratio = 1.760, 95% CI: 1.039-2.980; p = 0.035, respectively). Among OSA patients, the Mallampati score, tonsillar size, and BMI z-score were found to be significant for predicting OSA severity (odds ratio = 4.520, 95% CI: 1.332-15.335, p = 0.015, odds ratio = 9.177, 95% CI: 2.513-33.514, p = 0.001, and odds ratio = 2.820, 95% CI: 1.444-5.508; p = 0.002, respectively). Conclusion: The coexistence of the Mallampati score and BMI z-score significantly increases the presence of OSA in children. Mallampati score, tonsillar size, and BMI z-score are promising parameters for predicting OSA severity.

EFFECT OF ENLARGED ADENOIDS AND TONSILS ON BLOOD OXYGEN SATURATION IN AL BAHA, SAUDI ARABIA.

INTRODUCTION: The adenoids and palatine tonsils, part of the lymphoid tissue, act as a first line of defense protecting the lower airways and gastrointestinal tract. Adenotonsillar hypertrophy in children may lead to airway obstruction. This study aims to demonstrate the association between adenotonsillar hypertrophy and decreased blood oxygen saturation. METHODS: A retrospective cohort study was conducted among children aged 7-12 years with adenotonsillar hypertrophy and obstructive symptoms, admitted to King Fahad Hospital and Prince Mishari Hospital, Saudi Arabia, for tonsillectomy between July 2023 and January 2024. Exclusion criteria included respiratory diseases, cardiac disease, nasal polyps, nasal septum deviation, chest wall abnormality, and lower airway diseases. The control group included 56 healthy children. An otolaryngologist determined the severity of airway obstruction using the tonsil size. Oxygen saturation was measured using pulse oximetry. The determinants of oxygen saturation were assessed using multiple linear regression, with significance set at p<0.05. RESULTS: The study included 357 participants, with an even age distribution between 7-9 years (49.6%) and 10-12 years (50.4%), and 52% males. Diagnoses included adenoid hypertrophy (30%), tonsil hypertrophy (35%), both conditions (19%), and the control group (16%). Tonsil sizes ranged from Grade 1 (48%) to Grade 4 (8.4%), with 17% normal. The median oxygen saturation was 96.0% for the adenotonsillar hypertrophy group and 99.0% for the control. Oxygen saturation levels differed significantly across groups (p<0.0001), with lower median saturation in hypertrophy groups than controls. Males had a lower oxygen than females (estimate: -0.338, 95% CI [--0.640, -0.036], p=0.028). Adenoid hypertrophy (estimate: -3.863, 95% CI [-5.241, -2.484], p<0.001), tonsil hypertrophy (estimate: -3.631, 95% CI [-5.053, -2.208], p<0.001) and having both conditions (estimate: -3.777, 95% CI [-5.3.7, -2.247], p<0.001) was associated with lower oxygen saturation. Grade 1 tonsil size was associated with an increase in oxygen saturation (estimate = 2.905, 95% CI [1.616, 4.194], p<0.001). In contrast, Grade 4 tonsil size was linked to lower oxygen saturation (estimate=-4.848, 95% CI [-6.367, -3.329], p<0.001). Grades 2 and 3 were not significantly associated with changes in oxygen saturation. CONCLUSION: Adenotonsillar hypertrophy is significantly associated with decreased blood oxygen saturation and related cardiopulmonary complications in children. Early adenotonsillectomy may be of benefit in preventing these complications and improving oxygen saturation levels.

IgG4 Positivity in Chronic Tonsillitis: A New Component of IgG4-Related Disease?

OBJECTIVE: Immunoglobulin G4-related disease (IgG4-RD) and chronic tonsillitis are both chronic fibroinflammatory diseases in which tissue atrophy is sometimes observed. In this study, the authors aimed to investigate the pathologic IgG4 positivity in tonsillectomy specimens and hypothesized to name it as a new clinical component of IgG4-RD if there is significant IgG4 positivity in chronic tonsillitis. METHODS: A total of 73 patients who underwent tonsillectomy for chronic tonsillitis were included in this study. Of these, 31 patients had atrophic form chronic tonsillitis. Pathologic examinations and specific IgG4 immunohistochemical staining were performed by the same experienced pathologist in terms of IgG4-RD. RESULTS: Sixty-three percent (n=46) of the cases were male, 37% (n=27) were female, their ages ranged from 3 to 51, and the mean age was 19.11±14.82. It was determined that 23.3% (n=17) of the cases participating in the study were IgG4-positive. When the pathologic grades of the cases were examined; it was observed that 13.7% (n=10) were Grade I, 65.8% (n=48) were Grade II, and 20.5% (n=15) were Grade III. A statistically significant difference was found between the pathology degrees of the cases according to the IgG4 groups ( P =0.001; P <0.01). CONCLUSION: The authors concluded that as the histopathologic grades of chronic lymphoplasmacytic inflammation in tonsils specimen increase, IgG4 positivity rates also increase. Therefore, this clinical entity may be a new IgG4-related disease state in cases with chronic tonsillitis. LEVEL OF EVIDENCE: Level II.

Odynophagia as the first symptom of monkeypox infection.

A 50-year-old patient with confirmed monkeypox infection presented with odynophagia and nocturnal dyspnea. Clinically, there was a lesion on the tongue without any skin lesions and fibrinous plaques on the right tonsil with asymmetry of the palatoglossal arch. Due to a suggested abscess in the CT scan, a tonsillectomy à chaud was performed. By pan-orthopox-specific polymerase chain reaction (PCR) the monkeypox infection was also confirmed in the tonsil tissue. Isolated oral findings may represent a monkeypox infection and should be considered as a currently important differential diagnosis, especially for patients at risks.