Role of Tonsillar Chronic Inflammation and Commensal Bacteria in the Pathogenesis of Pediatric OSA.

Immune responses at the boundary between the host and the world beyond are complex and mucosal tissue homeostasis relies on them. Obstructive sleep apnea (OSA) is a syndrome suffered by children with hypertrophied tonsils. We have previously demonstrated that these tonsils present a defective regulatory B cell (Breg) compartment. Here, we extend those findings by uncovering the crucial role of resident pro-inflammatory B and T cells in sustaining tonsillar hypertrophy and hyperplasia by producing TNFα and IL17, respectively, in ex vivo cultures. Additionally, we detected prominent levels of expression of CD1d by tonsillar stratified as well as reticular epithelium, which have not previously been reported. Furthermore, we evidenced the hypertrophy of germinal centers (GC) and the general hyperplasia of B lymphocytes within the tissue and the lumen of the crypts. Of note, such B cells resulted mainly (IgG/IgM)+ cells, with some IgA+ cells located marginally in the follicles. Finally, by combining bacterial culture from the tonsillar core and subsequent identification of the respective isolates, we determined the most prevalent species within the cohort of OSA patients. Although the isolated species are considered normal oropharyngeal commensals in children, we confirmed their capacity to breach the epithelial barrier. Our work sheds light on the pathological mechanism underlying OSA, highlighting the relevance taken by the host immune system when defining infection versus colonization, and opening alternatives of treatment.

Limosilactobacillus reuteri ATCC PTA 5289 and DSM 17938 as adjuvants to improve evolution of pharyngitis/tonsillitis in children: randomised controlled trial.

Pharyngitis and tonsillitis are the most common acute respiratory infections (ARIs) in children aged ≤5 years. The analysis of published data showed that some probiotics could decrease the frequency and number of days with ARIs. This study evaluated the safety and efficacy of Limosilactobacillus reuteri ATCC PTA 5289 and DSM 17938 to reduce the duration and severity of ARI symptoms. This randomised controlled trial included children aged from 6 months to 5 years, with pharyngitis or tonsillitis, who were randomised to receive a probiotic product containing L. reuteri ATCC PTA 5289 and L. reuteri DSM 17938 or placebo, as drops, ingested orally for 10 days as adjuvants to the use of non-steroidal anti-inflammatory drugs. The main outcomes were the duration and severity of ARI symptoms. The secondary outcomes were changes in salivary immunoglobulin A and inflammatory biomarkers. There was no fever on day 2 and subsequent days in the L. reuteri group (37.3 ±0.5 °C vs 38.6±0.3 °C, P<0.05). Beginning on day 3, the severity of sore throat (5±0.9 vs 8±1.2, P<0.05) was lower in the L. reuteri group. Significant differences in the days with runny nose, nasal congestion, days of non-programmed visits to the medical office or emergency department, levels in tumoral necrosis factor-alpha (TNF-alpha) and related costs of treatment were observed in the L. reuteri group. The frequency of adverse events was similar between the groups. Therefore, L. reuteri ATCC PTA 5289 combined with L. reuteri DSM 17938 is a safe and effective adjunct to reduce the symptoms of pharyngitis or tonsillitis in children.

Characterization of tonsillar IL10 secreting B cells and their role in the pathophysiology of tonsillar hypertrophy.

The comprehension of unconventional immune functions of tonsillar B cells, their role in tolerance induction and protective immune responses, is crucial to unveil the dynamic interactions of the upper aero digestive tract with polymicrobial commensal flora and pathogens, in health and disease. Here, we describe the kinetics of IL10 intracellular expression and compare it with that of cytokines known to be produced by tonsillar B cells. Additionally, we detected a relevant proportion of IL17-expressing tonsillar B cells, which has not previously been reported. We immunophenotyped tonsillar IL10-expressing B cells (B10) and observed IL10 production in activated B cells at every developmental stage. Finally, we identified a relationship between decreased B10 percentages, increased proportion of the germinal centre (GC) population and hypertrophied tonsils (HT). Our findings provide greater insight into the role of B10 in GC reactions and characterized their involvement in the pathogenesis of tonsillar dysfunction.

Search for Herpesvirus 1 and 2 by in situ hybridization in tonsils and adenoids.

OBJECTIVE: Herpes simplex virus (HSV) has been described as cause of acute tonsillitis. It has also been found in nasopharyngeal florid lymphoid infiltrate, mostly composed of CD4+, CD56+ T-cells, simulating lymphoma. In spite of its widespread prevalence in latent form, to the best of our knowledge no study is available on in situ detection of HSV in chronically hyperplastic nasopharyngeal lymphoid tissue. The purpose of the present study was to search for the presence of HSV 1 and 2 in 21 adenoids and 15 tonsils from children (2-12 years of age) in which these organs had been surgically removed due to hypertrophy. METHODS: Paraffin wax-embedded sections from the 36 cases were submitted to the in situ hybridization technique, using the biotinilated probe to Herpes simplex virus 1 and 2 (Pan Path, Amsterdam) and the Rembrandt Universal DISH & HRP Detection Kit (Pan Path, Amsterdam). Positive control consisted of a previously tested Herpes infected lung. RESULTS: In none of the 36 cases studied were positive nuclei detected in adenoid and tonsils, either in lymphoid, in stroma or in epithelial cells, as those seen in the positive control. CONCLUSION: HSV does not seem to be implied in tonsil or adenoid chronic lymphoid hyperplasia. These organs do not seem to harbor the virus latently, or the amount of virus is too low to be detected without amplification methods.

Efecto del naproxeno sódico en las concentraciones séricas de IL-1, IL-6 y TFN en pacientes con faringoamigdalitis aguda purulenta / The effect of sodium naproxeno in the scrum concentration of IL-1, IL-6 and TNF in acute infectious process

Antecedentes. En el proceso infeccioso las citocinas producidas por los macrófagos y neutrófilos participan en los mecanismos de defensa del huésped. En estos mecanismos de fase aguda intervienen interleucinas como IL-1, IL-6 y el factor de necrosis tumoral (INF). Objetivo. Conocer el efecto del naproxeno sódico en las concentraciones séricas de IL-1, IL-6 y TNF, en un receso infeccioso agudo. Material y método. Se estudiaron al azar 18 pacientes, que se dividieron en dos grupos iguales, con diagnóstico clínico de faringoamigdalitis aguda purulenta. A un grupo se le dio naproxeno sódico y al otro placebo, ambos recibieron tratamiento antibacteriano con penicilina G procaínica. Resultados. El grupo que recibió naproxeno sódico tuvo disminución del síndrome febril e infeccioso a partir de las 72 horas. En los que recibieron placebo los síntomas y signos de los síndromes febril e infeccioso persistieron por más de tres días. Discusión. Los pacientes que recibieron tratamiento con naproxeno sódico tuvieron una disminución en la concentración sérica de IL-1B con diferencias estadísticamente significativas con respecto a las mediciones basal y a las 72 horas; también se observaron diferencias estadísticamente signficativas con los pacientes que recibieron placebo. Los resultados muestran que las concentraciones séricas de IL-1b disminuyeron en ambos grupos pero fue más acentuada la disminución en el grupo que recibió naproxeno sódico con disminución de los síntomas en forma más rápida

Amigdalites: aspectos imunológicos, microbiológicos e terapêuticos / Tonsillitis: imunologics, microbiologics and therapeutic aspects

As amígdalas têm peculiaridades anatômicas, e o fato de que existe uma relação entre as amígdalas e o sistema imunológico tem sido claramente demonstrado. Vírus e bactérias são capazes de estimular as células mononucleares das amígdalas, e podem ter um papel importante na etiologia das migdalites recorrentes e hipertróficas. Os autores revisam os aspectos mais importantes da imunologia e bacteriologia das amigdalites, bem como seu tratamento.

Tonsil do have anatomical peculiarities, and the fact that there is a relationship between tonsils and te immune system has been clearly demonstrated. Virus and bacteria are known to stimulate the tonsillar mononuclear cells and may play an important role in the etiology of recurrent and hypertrophic tonsillitis. The authors revise te most important aspectos of the immunology and bacteriology of tonsils, as wells as ist treatmento.

Inmunología de la IgA y las mucosas / Immunology of IgA and of mucosas

Aunque la relevancia clínica de la IgA en las enfermedades humanas no está completamente elucidada se conoce la gran importancia que desempeña la IgA como sistema de defensa contra las infecciones, tanto para virus y bacterias, como en la autoinmunidad y la alergia. Tiene un papel muy importante en caso de infecciones del tracto respiratorio alto y bajo, como en las amigdalitis, donde se ha demostrado que su presencia es indispensable para la inmunidad local. Existen argumentos en contra de las amigdalectomías, dado que es afectada la respuesta inmune específica de las mucosas y la IgA secretoria disminuye. Además, la amigdalectomía puede agravar aún más las infecciones del tracto respiratorio superior y predisponer a una mayor sensibilización a padecer asma y otras enfermedades alérgicas. El propósito de este artículo es relatar las primeras investigaciones que permitieron el conocimiento de la inmunología de las mucosas y elucidaron la función biológica de la IgA; para analizar desde el punto de vista inmunológico, las repercusiones que tiene para el sistema inmunitario la extirpación de las amígdalas, que es un órgano linfoide secundario

Amigdalite crônica / Chronic tonsillitis

O termo amigdalite crônica foi usado durante muito tempo para afecçöes repetitivas das amígdalas. Os patologistas têm empregado, de modo geral, este termo quando o exame das amígdalas encontram infiltrado linfoplasmocitário. Atualmente chamamos a este achado de reticulaçäo de cripta, sendo sinal de atividade amigdaliana. Os autores fazem estudo comparativo entre a história clínica do paciente e o laudo do exame histopatológico. Verificou-se que, mesmo em paciente sem queixas de amigdalites, o laudo do patologista era de amigdalite crônica. Os autores ainda sugerem uma nova classificaçäo das patologias amigdalianas baseadas nos graus de reticulaçäo, presença de plasmócitos, fases dos centros germinativos e suas quantidades

Amigdalite crônica: estudo imunohistoquímico e histológico / Cronic tonsilitis: inmunohistochemical and histologic study

Um estudo histológico e imunohistoquímico, foi realizado em 35 amígadas, provenientes de cirurgias em crianças de ambos os sexos com idade de 2 a 12 anos. Em todos os 35 pacientes havia indicaçäo histológico deu-se importância a presença de folículos linfóides, centros germinativos, presença ou näo de fibrose, necrose e presença ou näo de neutrófilos nas criptas. Segundo estes padröes e de acordo com a classificaçäo proposta por Lopes e Mimica em 1982, foram encontradas 22 classificáveis no grupo I e 13 no tipo II. Do ponto de vista imunológico, fez-se a análise imunohistoquímica do tecido amigdaliano, obedecendo-se a uma avaliaçäo quantitativa em campos histológicos e quantificadas as imunoglobulinas segundo a sua positividade em 100 células por campo, de uma cruz (+) a quatro cruzes. Em todas amígdalas estudadas houve um predomínio no encontro de IgG sobre a IgA, confirmando achados anteriores de Fioretti (1974). Nossos achados sugerem a existência de um quadro histológico e imunohistoquímico característico, na amigdalite crônica infantil