IL-1R8 expression in DLBCL regulates NK cell recruitment and influences patient prognosis.

The precise biological function of Interleukin-1 receptor 8 (IL-1R8) in diffuse large B-cell lymphoma (DLBCL) is still not well understood. Our goal is to decipher the profile of IL-1R8 expression status in DLBCL and to explore how IL-1R8 is involved in DLBCL progression. Utilizing a tissue microarray consisting of 70 samples of DLBCL tumors alongside 15 samples of tonsillitis, our investigation revealed a parallel expression profile of IL-1R8 between the tumor tissues and tonsillitis samples (p > 0.05). Nevertheless, an intriguing association emerged, as heightened expression of IL-1R8 correlated significantly with unfavorable survival outcomes in patients with DLBCL (p < 0.05). The status of IL-1R8 expression did not directly regulate proliferation (p > 0.05) and apoptosis (p > 0.05) in DLBCL cells via CCK8 and apoptotic assays. Subsequent chemotaxis analysis indicated that natural killer (NK) cell recruitment could be suppressed by IL-1R8 signaling in DLBCL, at least partially through CXCL1 inhibition (p < 0.05). The status of IL-1R8 expression in tumor tissues exhibited a negative correlation with the density of CD57+ NK cell infiltration (p < 0.05), while it did not demonstrate a significant association with CD3+ T cells (p > 0.05), CD68+ macrophages (p > 0.05), or S-100+ dendritic cells (p > 0.05). In line with this observation, elevated levels of NK cell infiltration demonstrated a significant positive correlation with improved overall survival (OS) among patients diagnosed with DLBCL (p < 0.05). Our data suggests the immuno-regulating potential of IL-1R8 through NK cell recruitment in DLBCL, providing novel insights into future immuno-modulating therapies.

ANTIBODIES TO MICROBIAL ANTIGENS AND CYTOKINES IN THE CELLS OF THE PALATINE TONSILS AND SERUM OF CHILDREN WITH PALATINE TONSILS HYPERTROPHY AND CHRONIC TONSILLITIS.

OBJECTIVE: The aim: The aim of the study is to compare the class G antibody content in serum and tissue lysate from tonsils of children with hypertrophy and chronic tonsillitis to: streptolysin-O of Str. haemolyticus, protein-A of S. aureus, proteoglycans of Klebsiela spp., as well as to compare the content of interleukins 1ß, 10, TNF-α, γ-IFN and lactoferrin in serum and tissue lysate from tonsils of children with hypertrophy and chronic tonsillitis. PATIENTS AND METHODS: Materials and methods: We studied tonsils of 33 children aged 4-18 years with hypertrophy of palatine tonsils (HPT) and with chronic tonsillitis (CT). The content of interleukins 1ß, 10, TNF-α, γ-IFN and lactoferrin in tonsil lysate and serum was determined by immunofluorescence assay. Antistreptolysin O was studied by neutralization test of micromethod; class G antibodies to protein A of S. aureus and proteoglycans of Klebsiela spp. were studied by treponema pallidum hemagglutination assay. All the results were statistically processed using U-test (Mann-Whitney-Wilcoxon test) and Fisher's z-transformation. RESULTS: Results: The serum and tissue lysate from tonsils of patients with HPT showed significantly high level of antibodies to streptolysin O in comparison with similar studies of substrates from patients with CT. Anti-inflammatory cytokine IL-10 was detected only in the serum of patients with CT. The TNF-α concentration in the lysates of tonsils in the group of patients with HPT was 2 times higher than in the group of patients with CT. The γ-IFN concentration was significantly lower both in the serum and in the lysates of tonsils of patients with CT. The content of lactoferrin in the lysates of patients with CT was 3 times higher (P<0.05) than in the lysates of patients with HPT. CONCLUSION: Conclusions: The results indicate a significant difference in the state of antibodies to microbial antigens and cytokines production in case of HPT and CT. In tonsils with HPT, there predominate reactions of antibody production to bacterial antigens and antiviral reactions like a high-level cytokines TNF-α and γ-IFN in tissue lysate of palatine tonsils.

Relationship of endoplasmic reticulum stress with the etiopathogenesis of chronic tonsillitis and tonsillar hypertrophy in pediatric patients: a prospective, parallel-group study.

OBJECTIVES: Tonsil tissue is a very important component of the human immunity system, contributing to the functioning of the cellular and humoral defence system, especially in childhood. The endoplasmic reticulum (ER) is an organelle that has a very important function in the balanced functioning of cells, in which the accumulation of a cellular protein called ER stress occurs in case of dysfunction. ER stress influences the pathogenesis of many diseases and immune system functions. We aimed to investigate the relation between the diseases of tonsil tissue and ER stress response to elucidate the mechanisms of diseases related with the immune system. METHODS: A prospective study was conducted in 46 children aged between 2 and 16 years who underwent tonsillectomy for chronic tonsillitis or tonsillar hypertrophy. Tonsil tissue was separated into two groups according to their size and evaluated in terms of ER stress markers and apoptosis markers by Real-time PCR and Western blot analysis. RESULTS: The ΔCT levels of ER stress markers (ATF4, ATF6, CHOP, GRP78, EIF2AK3, ERN1, GRP94) were greater in children with chronic tonsillitis (p < 0.005). In contrast, the tonsillar hypertrophy group had greater ΔCT levels of apoptosis markers (BAX, BCL-2) according to the Real-time PCR method (p < 0.005). According to the Western blot analysis, the normalized levels of ATF4, ATF6, CHOP, GRP78, and ERN1 genes were found greater in the chronic tonsillitis group than the tonsillar hypertrophy group. There was no difference between the two groups in terms of normalized BCL-2 and BAX levels by Western blot analysis. CONCLUSION: This is the first study in the literature investigating the effect of the ER stress pathway on the etiopathogenesis of tonsil diseases. It was concluded that the ER stress pathway plays a role in the etiopathogenesis of chronic tonsillitis. Investigating the relationship between ER stress and structures such as the tonsil tissue that make up the immune system can help create new treatment strategies. CLINICAL TRIAL REGISTRATION: Trial Registration ClinicalTrials.gov Identifier: NCT04653376.

Interaction between Ras and Bcl2L12 in B cells suppresses IL-10 expression.

The pathogenesis of recurrent tonsillitis is to be further investigated. B cell-derived interleukin (IL)-10 plays a critical role in immune regulation. Ras activation plays an important role in cancer and many immune disorders. This study aims to investigate the role of Ras activation in down regulating IL-10 expression in tonsillar B cells. Surgically removed tonsil tissues were collected from patients with recurrent acute tonsillar inflammation; B cells were isolated from the tonsillar tissues by flow cytometry sorting to be analyzed by the Ras-specific enzyme-linked immunosorbent assay and pertinent immunological approaches. We found that, compared to peripheral B cells (pBC), B cells isolated from the tonsillar tissues with recurrent inflammation (tBC) showed higher Ras activation, lower IL-10 expression and higher Bcl2L12 expression. Bcl2L12 formed a complex with GAP (GTPase activating protein) to prevent Ras from deactivating. The Ras activation triggered the MAPK/Sp1 pathway to promote the Bcl2L12 expression in B cells. Bcl2L12 prevented the IL-10 expression in tBCs, that was counteracted by inhibition of Ras or the Ras signal transduction pathway. In conclusion, Bcl2L12 interacts with Ras activation to compromise immune tolerance in the tonsils by inhibiting the IL-10 expression in tBCs. Inhibition of Bcl2L12 can restore the IL-10 expression in tBCs.

Spatially visualized single-cell pathology of highly multiplexed protein profiles in health and disease.

Deep molecular profiling of biological tissues is an indicator of health and disease. We used imaging mass cytometry (IMC) to acquire spatially resolved 20-plex protein data in tissue sections from normal and chronic tonsillitis cases. We present SpatialViz, a suite of algorithms to explore spatial relationships in multiplexed tissue images by visualizing and quantifying single-cell granularity and anatomical complexity in diverse multiplexed tissue imaging data. Single-cell and spatial maps confirmed that CD68+ cells were correlated with the enhanced Granzyme B expression and CD3+ cells exhibited enrichment of CD4+ phenotype in chronic tonsillitis. SpatialViz revealed morphological distributions of cellular organizations in distinct anatomical areas, spatially resolved single-cell associations across anatomical categories, and distance maps between the markers. Spatial topographic maps showed the unique organization of different tissue layers. The spatial reference framework generated network-based comparisons of multiplex data from healthy and diseased tonsils. SpatialViz is broadly applicable to multiplexed tissue biology.

Cytokine production in patients with recurrent acute tonsillitis: analysis of tonsil samples and blood.

The aim of this study was to examine T cell function in tonsils of patients with recurrent acute tonsillitis (RAT) or peritonsillar abscess (PTA) by analyzing the cytokine production following T cell receptor (TCR) and co-receptor stimulation with a combination of anti-CD3 and anti-CD28 antibodies. The release of IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A from isolated, stimulated T cells of 27 palatine tonsils (10 RAT, 7 PTA, 10 tonsils without inflammation) was measured via a bead-based flow cytometric analysis. The results were compared with the cytokine release of isolated peripheral T cells in a subset of the same patients (6 PTA, 4 patients without signs of inflammation in the blood). TCR stimulation increased the concentration of released cytokines in tonsil and blood as well as in different forms of inflammation and tissue with no inflammation. Stimulation increased the pro-inflammatory cytokines TNF-α, IFN-γ, and IL-2 more than the anti-inflammatory cytokines IL-4 and IL-10 in tonsil and blood samples in RAT, PTA, and samples without inflammation. Blood of patients with PTA showed a higher pro-inflammatory cytokine level compared to the samples of patients without inflammation. T cells in tonsils are fully responsive and competent for antigen-induced cytokine production in RAT and PTA. One should be aware that tonsillectomy, if indicated, might remove a functioning immune organ. Tonsillotomy might be an alternative even in adults to maintain immunological function.

Deciphering the fate of slan+ -monocytes in human tonsils by gene expression profiling.

Monocytic cells perform crucial homeostatic and defensive functions. However, their fate and characterization at the transcriptomic level in human tissues are partially understood, often as a consequence of the lack of specific markers allowing their unequivocal identification. The 6-sulfo LacNAc (slan) antigen identifies a subset of non-classical (NC) monocytes in the bloodstream, namely the slan+ -monocytes. In recent studies, we and other groups have reported that, in tonsils, slan marks dendritic cell (DC)-like cells, as defined by morphological, phenotypical, and functional criteria. However, subsequent investigations in lymphomas have uncovered a significant heterogeneity of tumor-infiltrating slan+ -cells, including a macrophage-like state. Based on their emerging role in tissue inflammation and cancer, herein we investigated slan+ -cell fate in tonsils by using a molecular-based approach. Hence, RNA from tonsil slan+ -cells, conventional CD1c+ DCs (cDC2) and CD11b+ CD14+ -macrophages was subjected to gene expression analysis. For comparison, transcriptomes were also obtained from blood cDC2, classical (CL), intermediate (INT), NC, and slan+ -monocytes. Data demonstrate that the main trajectory of human slan+ -monocytes infiltrating the tonsil tissue is toward a macrophage-like population, displaying molecular features distinct from those of tonsil CD11b+ CD14+ -macrophages and cDC2. These findings provide a novel view on the terminal differentiation path of slan+ -monocytes, which is relevant for inflammatory diseases and lymphomas.

[Proinflammatory cytokine content in the saliva of children suffering from chronic tonsillitis]. / Soderzhanie provospalitel'nykh tsitokinov v sliune detei s khronicheskim tonzillitom.

INTRODUCTION: We have examined 92 children aged between 6 and 15, suffering from chronic tonsillitis (CT). Tumor necrosis factor (TNF-α) and interleukin 1ß and 6 (IL-1ß and IL-6) contents have been defined in saliva. The control set comprised 17 healthy children. Cytokine content was defined with the enzyme multiplied immunoassay sets (Vektor Best Ltd., Russia) by enzyme-linked immunosorbent assay. The statistic analysis and data processing were carried out with statistic analysis programs (version 3.2, R Foundation for Statistical Computing, Vienna, Austria). RESULTS: The content of cytokines TNF-α, IL-1, IL-6 in CT children's saliva was high against the healthy children, yet the statistically significant differences were only noted for IL-6. In the CT group the median value of this factor (12.5) was significantly higher than in the control set (6.72) (p=0.01 in Mann-Whitney assessment). IL-6 was chosen as the basic factor for the mathematic model; its combinations in the form of a multi-factor logistic regression were given consideration. From out of the three possible models there was just one that had all the coefficients statistically significantly different from zero (TNF-α - IL-6). It was chosen as the basic diagnostic model for chronic tonsillitis. The created model's sensitivity is 80.4%, while its specificity is 82.4%. DISCUSSION: The revealed IL-6 dominance in saliva at CT can be is attributable to permanent antigenic challenge characteristic of the toxic allergic CT since, as previously shown, there are living proliferating microorganisms in the palatal tonsil tissues and their blood- and lymph vessels at CT. CONCLUSION: The conducted ROC-analysis has demonstrated high sensitivity and specificity of the mathematical model, which enabled us to recommend determination of IL-6 in the saliva of the children suffering from CT as an additional diagnostic criterion.

Prevalence of humoral immunodeficiency in adult patients with recurrent tonsillitis.

PURPOSE: Recurrent tonsillitis in adults has a significant impact on patients' daily life and healthcare costs. Humoral immunodeficiency increases the susceptibility to recurrent infections. The purpose of this study was to investigate the prevalence and contribution of humoral immunodeficiency in adult patients with recurrent tonsillitis. MATERIAL AND METHODS: A prospective cross-sectional study conducted over 3 years duration with two groups of subjects. Group 1: included 50 normal adult subjects and group 2: included 50 adult patients with recurrent tonsillitis. Recruitment occurred in a tertiary care hospital in Egypt. Different immunoglobulins (Ig A, Ig M and Ig G isotypes) were quantitatively assessed and compared in 2 groups. Incidence of different infections was also compared in patients with humoral immunodeficiency versus patients with intact immunity. RESULTS: 4 (8%) subjects in group 1 had selective humoral Immunodeficiency versus 13 (26%) patients in group 2. Patients with recurrent tonsillitis had significantly lower mean of most assessed immunoglobulins: IgA (P = 0.002), IgM (P = 0.003), IgG (P < 0.0001), IgG1 (P < 0.0001) and IgG3 (P < 0.0001) compared to normal subjects; with no significant difference in mean of IgG2 (P = 0.395) and IgG4 (P = 0.105). Patients with humoral immunodeficiency had significantly higher incidence of tonsillitis (P < 0.0001) and rhinosinusitis (P < 0.0001) attacks compared to patients with normal immunity. CONCLUSION: Adult patients with recurrent tonsillitis may have higher prevalence of humoral immunodeficiency compared to normal subjects. These findings suggest that assessment of immune function should be undertaken routinely in these patients.

The differences in the expression of fractalkine and its receptor in conditions of tonsillar hypertrophy and chronic tonsillitis.

OBJECTIVE: Fractalkine, member of chemokine family, is involved in many inflammatory processes in the human body. The aim of this study is to compare expression levels of fractalkine ligand and its receptor in chronic tonsillitis and hypertrophic tonsil samples. METHODS: The study was conducted at Baskent University Departments of Otorhinolaryngology and Medical Genetics. It is designed as a prospective, non-randomized, controlled clinical study. Total 97 samples, obtained from adenotonsillectomy due to chronic tonsillitis or tonsillar hypertrophy, were participated in the study. Fractalkine and its receptor expression levels were determined and comparison was made between the tissue groups. c.839C>T (T280M) polymorphism of fractalkine receptor was analyzed, then relationship between polymorphism and the expression level of fractalkine receptor was investigated. RESULTS: Fractalkine receptor expression was significantly higher in the hypertrophic tonsil group than chronic tonsillitis group (p<0.05). CONCLUSION: Fractalkine, member of chemokine family, and its receptor may play role in preventing chronic-recurrent tonsillitis.

Differential chemokine expression patterns in tonsillar disease.

Expression profiles of CXC- and CC-chemokines in various forms of tonsillar disease were studied to evaluate whether certain chemokines play a predominant role in a specific subset of tonsillar disease. Total RNA was isolated from 89 biopsies (21 hyperplastic palatine tonsils, 25 adenoids, 16 chronic inflammatory palatine tonsils and 27 chronic inflammatory palatine tonsils with histological prove of acute inflammation), reverse transcribed and subjected to PCR amplifying IL-8, Gro-alpha, eotaxin-1, eotaxin-2, MCP-3, MCP-4 and RANTES. 2% agarose gel electrophoresis revealed a predominance of IL-8 in the chronic inflammatory palatine tonsil group compared to tonsillar hyperplasia. Furthermore, eotaxin-2 was strongly overexpressed in adenoid samples compared to chronic inflammatory specimens. Our data suggest that the majority of diseases related to adenoid formation are mediated via an eotaxin-2 expression, whereas chronic inflammatory tonsillitis is associated with IL-8 upregulation. These data imply that adenoids are related to a Th-2, and chronic inflammatory tonsillitis to a Th-1 based immune response.

DYNAMICS OF CONTENT OF SOME MINERALS IN TEENAGERS WITH CARDIOVASCULAR SYSTEM PATHOLOGY AGAINST THE BACKGROUND OF CHRONIC TONSILLITIS ZMIANY ZAWARTOSCI NIEKTÓRYCH SKLADNIKÓW MINERALNYCH U MLODZIEZY Z CHOROBAMI UKLADU SERCOWO-NACZYNIOWEGO JAKO PODLOZE ROZWOJU PRZEWLEKLEGO ZAPALENIA MIGDALKÓW PODNIEBIENNYCH.

OBJECTIVE: Introduction: Chronic diseases of the upper respiratory tract in children and teenagers, such as chronic tonsillitis is quite common in pediatric populations, accompanied by changes in reactivity, causing a risk of complications. Due to the fact that the child's body resistance to acute infectious diseases depends on the sufficiency of trace elements, then at present stage greatly increased interest in deeper study of exchange of macro- and microelements in the human body in normal and pathological conditions. The aim: To study the dynamics of zinc, iron, potassium and magnesium in adolescents with disorders of the cardiovascular system with chronic tonsillitis. PATIENTS AND METHODS: Materials and methods: It was examined 63 patients with chronic tonsillitis, among them- 31 children suffer from chronic tonsillitis off-damage to the cardiovascular system (I group), 32 patients with disorders of the cardiovascular system against the background of chronic tonsillitis (II group). The content of trace elements zinc, iron, minerals potassium and magnesium was analyzed. The measurement and calculation were done according to AAS-SPECTR program. Analysis and statistics treatment was done on using application programs STATISTICA 7.0 and MS Excel XP. RESULTS: Results: In result of investigation it was found a violation of trace element composition in the blood serum. Thus, in patients with chronic tonsillitis without cardiovascular system damage during hospitalization was observed a significant decrease in the concentration of iron to (15,47 ± 1,12) mmol/l. Similar changes were observed with the concentration of zinc in the blood serum. In patients with chronic tonsillitis without cardiovascular system damage during hospitalization was observed a significant decrease in the concentration of iron to (15,47 ± 1,12) mmol/l. Similar changes were observed with the concentration of zinc in the blood serum of patients of I groups during hospitalization (10,89 ± 0,57mmol/l) and was significantly lower compared with the data of healthy children (18,40 ± 0,71 mmol/l (p <0.05)). CONCLUSION: Сonclusions: It should be noted that children with tonsillogene cardiac lesions during hospitalization have a significant decreasing in the level of magnesium compared with indicators of children without pathology of the cardiovascular system. After treatment, the normalization of trace elements iron, zinc, magnesium did not happen, moreover, significant changes were observed in patients with heart disease against the background of chronic tonsillitis.

Tonsillar antimicrobial peptide (AMP) expression profiles of periodic fever, aphthous stomatitis, pharyngitis, cervical adenitis (PFAPA) patients.

INTRODUCTION: PFAPA (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis) is the most frequent non-infectious cause of high fever observed among the European child population. While its cause is still not yet fully identified, PFAPA patients were previously shown to have altered tonsillar microbiome composition. Our study hypothesized that this is associated with a change in antimicrobial peptide (AMP) expression levels, as in the case of Crohn's disease which is another autoinflammatory disorder. METHODS AND MATERIALS: The tonsil specimens were isolated from seven patients with PFAPA syndrome, and six patients with group A beta-hemolytic streptococcal (GAßHS) recurrent tonsillitis. Tonsillar expression levels of human beta-defensin 1-2, cathelicidin, ribonuclease-7, and liver expressed antimicrobial peptide-1 were monitored by immunohistochemistry (IHC). Expression levels were scored using semi-quantitative analysis method and were statistically analyzed by Two-Way Repeated Measures Analysis of Variance test. RESULTS: Our results showed no significant difference in AMP expression levels between PFAPA and GAßHS patients. Immunolocalization of human beta-defensin 1 was different between the two groups; expressed at higher levels on tonsil surface epithelium (SE) than lymphoid interior (LI) in PFAPA patient group, while this was not evident in GAßHS patients group. CONCLUSIONS: Our results suggest that, PFAPA patients may be associated with altered AMP expression as in other autoinflammatory diseases. Future studies with subjects without any inflammatory condition are required for more precise conclusions.

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.

Alteration of thiol-disulphide homeostasis in acute tonsillopharyngitis.

OBJECTIVE: Thiol-disulphide homeostasis (TDH) has a critical role in various clinical disorders. We aimed to assess the association of TDH with acute tonsillopharyngitis (AT) in children. METHODS: This study included 94 (73 viral and 21 bacterial) tonsillopharyngitis patients and 88 control children. Their native thiol, total thiol, and disulphide levels were measured. RESULTS: Viral and bacterial tonsillopharyngitis patients had lower native thiol levels compared with healthy children (P < 0.001 and P = 0.008, respectively). Both groups had lower total thiol levels compared with control children (P = 0.002 for viral, P = 0.011 for bacterial). The disulphide levels were lower in bacterial than in viral tonsillopharyngitis patients (P = 0.04), and there was a significant difference between viral tonsillopharyngitis patients and the control group (P < 0.001). The native/total thiol ratio in each patient group was lower than in the control group (P < 0.001 for viral, P = 0.017 for bacterial). The disulphide/native thiol and disulphide/total thiol ratios were significantly higher in viral (P < 0.001 for both) and bacterial tonsillopharyngitis patients (P = 0.017 for both) than in healthy children. In all patients, a correlation was found between the levels of C-reactive protein (CRP) and native thiol (r = -0.211, P = 0.04), CRP and total thiol (r = -0.217, P = 0.036), white blood cell (WBC) and native thiol (r = -0.228, P = 0.002), WBC and total thiol (r = -0.191, P = 0.01), and WBC and disulphide (r = 0.160, P = 0.03). DISCUSSION: TDH is altered in AT in children. The alteration is more prominent in viral than in bacterial tonsillopharyngitis.

Advanced oxidation protein product levels as a marker of oxidative stress in paediatric patients with chronic tonsillitis.

We aimed to determine whether advanced oxidation protein product (AOPP) levels can serve as a marker of oxidative stress in paediatric patients with chronic tonsillitis. Thirty children with chronic tonsillitis and 30 healthy children (control group) were recruited from the Otorhinolaryngology (ORL) and Paediatric Surgery departments, respectively, of Dumlupinar University Hospital. In the patient group, blood samples were collected before tonsillectomy, and tonsil tissue was sampled during the operation. Blood samples were also obtained from the control subjects. AOPP levels in the serum and tonsil tissue were measured by the spectrophotometric method. Serum AOPP levels were significantly higher in the patient group (13.1 ± 3.3 ng/ml) than in the control group (11.6 ± 2.3 ng/ml; P < 0.05). In addition, the mean AOPP level (41.9 ± 13.5 ng/mg protein) in the tonsil tissue in the patient group was significantly higher than the mean serum AOPP levels in the control and patient groups (P < 0.05). AOPP levels are elevated in the tonsil tissue and serum of patients with chronic tonsillitis compared to the serum AOPP levels in healthy controls. AOPPs may represent a novel class of pro-inflammatory molecules that are involved in oxidative stress in chronic tonsillitis. AOPPs may be used as a marker of oxidative stress in paediatric patients with chronic tonsillitis.

Expression and Localization of Human Defensins in Palatine Tonsils.

Defensins are small antimicrobial peptides and effector components of innate immune responses. Recent studies have shed light on their beneficial functions for the prevention of infection and potential for development of new drugs. Here, we showed the expression profiles of human defensins in palatine tonsils with 3 different diseases: tonsillar hypertrophy, recurrent tonsillitis and focal infection of the tonsil. RT-PCR analysis and immunofluorescence revealed that the expression of human α-defensin 4 and ß-defensin 3 (ß3) in palatine tonsils with tonsillar hypertrophy was lower than that in recurrent tonsillitis and focal infection of the tonsil, suggesting that chronic inflammation induces defensin expression. Interestingly, ß2 and ß3 mRNAs were specifically expressed by palatine tonsil tissues but not in human peripheral blood mononuclear cells and mucosa of the small intestine. Additionally, we observed that exposure to a Toll-like receptor 4 ligand, lipopolysaccharide, which is used as a bacterial infection model, increases the production of ß2 in culture supernatants from tonsillar epithelial cells in a dose-dependent manner. Taken together, these results indicate that ß2 produced by tonsillar epithelial cells plays an important role in the innate immune response for bacterial infections.

Infection biomarkers in primary care patients with acute respiratory tract infections-comparison of Procalcitonin and C-reactive protein.

BACKGROUND: There is a lack of studies comparing the utility of C-reactive protein (CRP) with Procalcitonin (PCT) for the management of patients with acute respiratory tract infections (ARI) in primary care. Our aim was to study the correlation between these markers and to compare their predictive accuracy in regard to clinical outcome prediction. METHODS: This is a secondary analysis using clinical and biomarker data of 458 primary care patients with pneumonic and non-pneumonic ARI. We used correlation statistics (spearman's rank test) and multivariable regression models to assess association of markers with adverse outcome, namely days with restricted activities and persistence of discomfort from infection at day 14. RESULTS: At baseline, CRP and PCT did not correlate well in the overall population (r(2) = 0.16) and particularly in the subgroup of patients with non-pneumonic ARI (r(2) = 0.08). Low correlation of biomarkers were also found when comparing cut-off ranges, day seven levels or changes from baseline to day seven. High baseline levels of CRP (>100 mg/dL, regression coefficient 1.6, 95 % CI 0.5 to 2.6, sociodemographic-adjusted model) as well as PCT (>0.5ug/L regression coefficient 2.0, 95 % CI 0.0 to 4.0, sociodemographic-adjusted model) were significantly associated with larger number of days with restricted activities. There were no associations of either biomarker with persistence of discomfort at day 14. CONCLUSIONS: CRP and PCT levels do not well correlate, but both have moderate prognostic accuracy in primary care patients with ARI to predict clinical outcomes. The low correlation between the two biomarkers calls for interventional research comparing these markers head to head in regard to their ability to guide antibiotic decisions. TRIAL REGISTRATION: Current Controlled Trials, ISRCTN73182671.

The role of tonsillectomy in IgA nephropathy.

The IgA nephropathy (IgAN) is a very common glomerulonephritis and can result in end-stage renal disease. From a clinical point of view, IgAN is characterised by repeated events of macrohaematuria associated with infections of the upper airways. In IgAN, the IgA released by the tonsillar lymphatic tissue into blood circulation are defective in glycosylation. These aberrant IgA can reach the glomeruli and deposit into mesangium causing an inflammation with cellular proliferation. The treatment is not yet well defined: steroids and immunosuppressive drugs are suggested in cases with a progressive disease. Tonsillectomy was proposed to reduce the infective events of upper airways and the lymphatic tissue producing undergalactosylated IgA. The experiences in literature coming from Asia report positive effects of tonsillectomy on IgAN. In patients with tonsillectomy, the renal signs improved (less haematuria and proteinuria) and the renal outcome was better (slower progression of renal damage). These were uncontrolled studies and tonsillectomy was associated with steroid and immunosuppressive treatment, so it is not possible to tell the real effect of tonsillectomy. In contrast, the European studies reported that the tonsillectomy was not associated with a better outcome of IgAN. A critical review of the subject reveals that most of the papers with positive results were uncontrolled retrospective experiences, while in a randomised controlled trial paper the advantages of tonsillectomy disappeared. In conclusion, this review, in agreement with the international guidelines, concludes that tonsillectomy does not play any role in the progression of IgAN.

Reduction in oxidative stress biomarkers after adenotonsillectomy.

OBJECTIVES: A number of otolaryngic conditions such as chronic tonsillitis, adenoid hypertrophy, and obstructive sleep apnea are associated with oxidative stress and elevated levels of serum oxidants. The objective of this study is to measure changes in urine biomarkers of oxidative stress in children after adenotonsillectomy. METHODS: Twenty-two children with sleep disordered breathing (SDB) with tonsil and adenoid hypertrophy were enrolled prior to adenotonsillectomy. Controls consisted of 20 healthy children. Urine samples were collected from all patients. Levels of three urinary biomarkers for oxidative status, 8-hydroxy-2-deoxyguanosine (8-OxodG), F(2)-isoprostane, and malondialdehyde (MDA) were measured using high performance liquid chromatography. For the study group, urine samples were repeated 3 weeks after surgery. RESULTS: In the study group, preoperative urinary levels of 8-OxodG were higher than in controls (p=0.015). Levels decreased after surgery compared to preoperative levels (p=0.002), and reached control levels (p=0.167) at 3 weeks. Levels of urinary F(2)-isoprostane were similar in both groups (p=0.252), but decreased significantly after surgery (p=0.020). CONCLUSIONS: Children with SDB have elevated levels of urinary 8-OxodG, a marker of oxidative stress. Adenotonsillectomy results in decreased 8-OxodG and F(2)-isoprostane. These findings suggest that urine analysis may represent a valuable tool for the measurement of oxidative stress.