TLR activation, immune response and viral protection elicited in cattle by a commercial vaccine against Bovine Herpesvirus-1.

The innate and acquired immune response induced by a commercial inactivated vaccine against Bovine Herpesvirus-1 (BoHV-1) and protection conferred against the virus were analyzed in cattle. Vaccination induced high levels of BoHV-1 antibodies at 30, 60, and 90 days post-vaccination (dpv). IgG1 and IgG2 isotypes were detected at 90 dpv, as well as virus-neutralizing antibodies. An increase of anti-BoHV-1 IgG1 in nasal swabs was detected 6 days post-challenge in vaccinated animals. After viral challenge, lower virus excretion and lower clinical score were observed in vaccinated as compared to unvaccinated animals, as well as BoHV-1-specific proliferation of lymphocytes and production of IFNγ, TNFα, and IL-4. Downregulation of the expression of endosome Toll-like receptors 8-9 was detected after booster vaccination. This is the first thorough study of the immunity generated by a commercial vaccine against BoHV-1 in cattle.

A systems genomics approach uncovers molecular associates of RSV severity.

Respiratory syncytial virus (RSV) infection results in millions of hospitalizations and thousands of deaths each year. Variations in the adaptive and innate immune response appear to be associated with RSV severity. To investigate the host response to RSV infection in infants, we performed a systems-level study of RSV pathophysiology, incorporating high-throughput measurements of the peripheral innate and adaptive immune systems and the airway epithelium and microbiota. We implemented a novel multi-omic data integration method based on multilayered principal component analysis, penalized regression, and feature weight back-propagation, which enabled us to identify cellular pathways associated with RSV severity. In both airway and immune cells, we found an association between RSV severity and activation of pathways controlling Th17 and acute phase response signaling, as well as inhibition of B cell receptor signaling. Dysregulation of both the humoral and mucosal response to RSV may play a critical role in determining illness severity.

Early nasal type I IFN immunity against SARS-CoV-2 is compromised in patients with autoantibodies against type I IFNs.

IFN-I and IFN-III immunity in the nasal mucosa is poorly characterized during SARS-CoV-2 infection. We analyze the nasal IFN-I/III signature, namely the expression of ISGF-3-dependent IFN-stimulated genes, in mildly symptomatic COVID-19 patients and show its correlation with serum IFN-α2 levels, which peak at symptom onset and return to baseline from day 10 onward. Moreover, the nasal IFN-I/III signature correlates with the nasopharyngeal viral load and is associated with the presence of infectious viruses. By contrast, we observe low nasal IFN-I/III scores despite high nasal viral loads in a subset of critically ill COVID-19 patients, which correlates with the presence of autoantibodies (auto-Abs) against IFN-I in both blood and nasopharyngeal mucosa. In addition, functional assays in a reconstituted human airway epithelium model of SARS-CoV-2 infection confirm the role of such auto-Abs in abrogating the antiviral effects of IFN-I, but not those of IFN-III. Thus, IFN-I auto-Abs may compromise not only systemic but also local antiviral IFN-I immunity at the early stages of SARS-CoV-2 infection.

Association Between Microbiota and Nasal Mucosal Diseases in terms of Immunity.

The pathogenesis of nasal inflammatory diseases is related to various factors such as anatomical structure, heredity, and environment. The nasal microbiota play a key role in coordinating immune system functions. Dysfunction of the microbiota has a significant impact on the occurrence and development of nasal inflammation. This review will introduce the positive and negative roles of microbiota involved in immunity surrounding nasal mucosal diseases such as chronic sinusitis and allergic rhinitis. In addition, we will also introduce recent developments in DNA sequencing, metabolomics, and proteomics combined with computation-based bioinformatics.

Intranasal levels of lead as an exacerbation factor for allergic rhinitis in humans and mice.

BACKGROUND: Air pollutants are suspected to affect pathological conditions of allergic rhinitis (AR). OBJECTIVES: After detecting Pb (375 µg/kg) in Japanese cedar pollen, the effects of intranasal exposure to Pb on symptoms of AR were investigated. METHODS: Pollen counts, subjective symptoms, and Pb levels in nasal epithelial lining fluid (ELF) were investigated in 44 patients with Japanese cedar pollinosis and 57 controls from preseason to season. Effects of intranasal exposure to Pb on symptoms were confirmed by using a mouse model of AR. RESULTS: Pb levels in ELF from patients were >40% higher than those in ELF from control subjects during the pollen season but not before the pollen season. Pb level in ELF was positively associated with pollen counts for the latest 4 days before visiting a hospital as well as scores of subjective symptoms. Intranasal exposure to Pb exacerbated symptoms in allergic mice, suggesting Pb as an exacerbation factor. Pb levels in ELF and nasal mucosa in Pb-exposed allergic mice were higher than those in Pb-exposed nonallergic mice, despite intranasally challenging the same amount of Pb. Because the increased Pb level in the nasal mucosa of Pb-exposed allergic mice was decreased after washing the nasal cavity, Pb on the surface of but not inside the nasal mucosa may have been a source of increased Pb level in ELF of allergic mice. CONCLUSIONS: Increased nasal Pb level partially derived from pollen could exacerbate subjective symptoms of AR, indicating Pb as a novel hazardous air pollutant for AR.

Pre-existing influenza-specific nasal IgA or nasal viral infection does not affect live attenuated influenza vaccine immunogenicity in children.

The United Kingdom has a national immunization programme which includes annual influenza vaccination in school-aged children, using live attenuated influenza vaccine (LAIV). LAIV is given annually, and it is unclear whether repeat administration can affect immunogenicity. Because LAIV is delivered intranasally, pre-existing local antibody might be important. In this study, we analysed banked samples from a study performed during the 2017/18 influenza season to investigate the role of pre-existing influenza-specific nasal immunoglobulin (Ig)A in children aged 6-14 years. Nasopharyngeal swabs were collected prior to LAIV immunization to measure pre-existing IgA levels and test for concurrent upper respiratory tract viral infections (URTI). Oral fluid samples were taken at baseline and 21-28 days after LAIV to measure IgG as a surrogate of immunogenicity. Antibody levels at baseline were compared with a pre-existing data set of LAIV shedding from the same individuals, measured by reverse transcription-polymerase chain reaction. There was detectable nasal IgA specific to all four strains in the vaccine at baseline. However, baseline nasal IgA did not correlate with the fold change in IgG response to the vaccine. Baseline nasal IgA also did not have an impact upon whether vaccine virus RNA was detectable after immunization. There was no difference in fold change of antibody between individuals with and without an URTI at the time of immunization. Overall, we observed no effect of pre-existing influenza-specific nasal antibody levels on immunogenicity, supporting annual immunization with LAIV in children.

Evaluation of the upper airway microbiome and immune response with nasal epithelial lining fluid absorption and nasal washes.

Despite being commonly used to collect upper airway epithelial lining fluid, nasal washes are poorly reproducible, not suitable for serial sampling, and limited by a dilution effect. In contrast, nasal filters lack these limitations and are an attractive alternative. To examine whether nasal filters are superior to nasal washes as a sampling method for the characterization of the upper airway microbiome and immune response, we collected paired nasal filters and washes from a group of 40 healthy children and adults. To characterize the upper airway microbiome, we used 16S ribosomal RNA and shotgun metagenomic sequencing. To characterize the immune response, we measured total protein using a BCA assay and 53 immune mediators using multiplex magnetic bead-based assays. We conducted statistical analyses to compare common microbial ecology indices and immune-mediator median fluorescence intensities (MFIs) between sample types. In general, nasal filters were more likely to pass quality control in both children and adults. There were no significant differences in microbiome community richness, α-diversity, or structure between pediatric samples types; however, these were all highly dissimilar between adult sample types. In addition, there were significant differences in the abundance of amplicon sequence variants between sample types in children and adults. In adults, total proteins were significantly higher in nasal filters than nasal washes; consequently, the immune-mediator MFIs were not well detected in nasal washes. Based on better quality control sequencing metrics and higher immunoassay sensitivity, our results suggest that nasal filters are a superior sampling method to characterize the upper airway microbiome and immune response in both children and adults.

Nasal reactivity evaluation in children with allergic rhinitis receiving grass pollen sublingual immunotherapy.

Background: The European Academy of Allergy and Clinical Immunology guidelines, strongly recommended allergen immunotherapy (AIT) as an effective treatment to achieve long-term clinical benefits and to modify the natural history of allergic diseases. Sublingual immunotherapy (SLIT) offers the possibility of home administration, which improves patient comfort and compliance. Objective: The primary outcome of this study was to assess the change in nasal reactivity after grass-pollen AIT treatment. Methods: This was a monocentric, prospective, observational study conducted in Rome from September 2016 to June 2018, in the Pediatric Department of Policlinico Umberto I. We enrolled children, ages between 6 and 12 years, with persistent allergic rhinitis (AR), sensitized to grass pollen. At the first visit (V0, September 2016), one group received the first dose of oral immunotherapy for grass-pollen spray buccal and the other group continued only standard therapy. All the patients had nasal specific immunoglobulin I (IgE) assay (Phl p1, Phl p5), active anterior rhinomanometry with a nasal provocation test (NPT), and spirometry. The patients attended two follow-up visits, in May 2017 (V1) and May 2018 (V2), with the same examinations as at V0. Results: During the treatment, we observed, in the treated group, a significant increase in the mean nasal flow compared with untreated children (p < 0.001). In the AIT group, we found an improvement of nasal function and only 21.05% of all the children in the active group with a positive NPT result at V2. In the control group, we found, at V2, a worsening of nasal function, with 89.47% of the children with a positive NPT result. Furthermore, we found a significant reduction of nasal specific IgE levels at the end of the observation period in the treated group. Conclusion: Analysis of our data provided evidence for a clinical effect of SLIT in inducing clinical changes and allergen tolerance in children with AR.

Intranasal Bifidobacterium longum protects against viral-induced lung inflammation and injury in a murine model of lethal influenza infection.

BACKGROUND: Prophylactic strategies are urgently needed for prevention of severe inflammatory responses to respiratory viral infections. Bacterial-host interactions may modify the immune response to viral infections. METHODS: We examined the contribution of Intranasal administration of two different Bifidobacterium longum strains or its isolated cell wall in controlling viral induced inflammation using a murine model of influenza infection. We monitored mortality and morbidity over a 10-day period and viral load, differential broncho alveolar lavage (BAL) fluid inflammatory cell counts, Lung tissue histology, BAL and serum cytokines, markers of vascular damage and cell death were quantified. FINDINGS: Intranasal administration of Bifidobacterium longum35624® or its isolated cell wall prior to virus inoculation significantly reduced viral load within the lungs and significantly improved survival. Reduced viral load was associated with reduced lung injury as suggested by cell death and vascular leakage markers, a shift from neutrophil to macrophage recruitment, reduced inflammatory cytokine levels (including IL-6), reduced type 1 and 2 interferon levels, but increased levels of interferon-λ and surfactant protein D. These protective effects were maintained when the bifidobacterial cell wall preparation was administered 24 h after viral inoculation. The protective effects were also observed for the Bifidobacterium longumPB-VIR™ strain. INTERPRETATION: Exposure to these bifidobacterial strains protect against the inflammatory sequelae and damage associated with uncontrolled viral replication within the lung. FUNDING: This work has been funded, in part, by a research grant from GlaxoSmithKline, PrecisionBiotics Group Ltd., Swiss National Science Foundation grants (project numbers CRSII3_154488, 310030_144219, 310030_127356 and 310030_144219) and Christine Kühne - Center for Allergy Research and Education (CK-CARE).

Potential Differences between Local and Systemic Allergic Rhinitis Induced by Birch Pollen.

INTRODUCTION: Different endotypes of rhinitis are known, but its pathomechanism has not been conclusively established. For example, the precise difference between systemic allergic rhinitis (SAR) and local allergic rhinitis (LAR) is still being checked. Comparison of patients with LAR and with allergies to birch of those with intermittent allergic rhinitis, same allergy, or with non-allergic rhinitis (NAR) was the purpose of this study. METHODS: Twenty-six patients with LAR, 18 with SAR and allergy to birch, and 21 with NAR were included. Patients who met the inclusion criteria were selected to undergo the following procedures at baseline: medical examinations, nasal provocation test (NPT), detection of nasal-specific IgE to birch as well as basophil activation test (BAT). All immunological parameters were detected before and after NPT. RESULTS: Concentration of nasal IgE to Bet v1 increased comparably in the LAR and SAR groups after NPT to birch as follows: in 21 (81%) patients with LAR, 14 (78%) with SAR, and in everyone in the NAR group. Serum concentration of allergen-specific IgE to Bet v1 increased significantly from a median of 20.7 (25-75% interval: 11.2-35.6) IU/mL to 29.9 (13.6-44.1) (p = 0.028) after NPT in patients with SAR. Allergen-specific IgE to Bet v1 was absent in all patients with LAR and NAR before and after NPT. BAT with Bet v1 was positive in 22 (85%) patients with LAR, in 14 (78%) with SAR, and 2 (9.5%) with NAR. CONCLUSION: These obtained data suggest there are no potential mechanisms that could explain LAR compared to SAR.

World Trade Center Dust induces airway inflammation while promoting aortic endothelial dysfunction.

Respiratory ailments have plagued occupational and public health communities exposed to World Trade Center (WTC) dust since the September 11, 2001 attack on the Twin Towers in Lower Manhattan. We proposed that these ailments were proposed to be induced by inhalation exposure to WTC particulate matter (WTCPM), that was released during the collapse of the buildings and its subsequent resuspension during cleanup. We investigated this hypothesis using both an in vitro and an in vivo mouse intranasal (IN) exposure models to identify the inflammatory potential of WTCPM with specific emphasis on respiratory and endothelial tissue responses. The in vitro exposure studies found WTCPM exposure to be positively correlated with cytotoxicity and increased NO2- production in both BEAS-2B pulmonary epithelial cells and THP-1 macrophage cells. The in vivo C57BL/6 mouse studies found significant increases in inflammatory markers including increases in polymorphonuclear neutrophil (PMN) influx into nasal and bronchoalveolar lavage fluids (NLF and BALF), as well as increased levels of total protein and cytokine/chemokines levels. Concurrently, NLF, BALF, and serum NO2- levels exhibited significant homeostatic temporal deviations as well as temporal myograohic aortic dysfunction in myography studies. Respiratory exposure to- and evidence -based retention of- WTCPM may have contributed to chronic systemic effects in exposed mice that r resembled to observed effects in WTCPM-exposed human populations. Collectively, these findings are reflective of WTCPM exposure and its effect(s) on respiratory and aortic tissues, highlighting potential dysfunctional pathways that may precipitate inflammatory events, while simultaneously altering homeostatic balances. The tight interplay between these balances, when chronically altered, may contribute to- or result in- chronically diseased pathological states.

Assessment of respiratory and systemic toxicity of Benzalkonium chloride following a 14-day inhalation study in rats.

BACKGROUND: Although biocides at low concentrations have been used to control pests, they can be more harmful than industrial chemicals as humans are directly and frequently exposed to such biocides. Benzalkonium chloride (BAC or BKC) is a non-toxic substance used to control pests. Recently, BAC has been increasingly used as a component in humidifier disinfectants in Korea, raising a serious health concern. Moreover, it poses significant health hazards to workers handling the chemical because of direct exposure. In the present study, we aimed to evaluate the respiratory toxicity of BAC due to its inhalation at exposure concentrations of 0.8 (T1 group), 4 (T2 group) and 20 (T3 group) mg/m3. RESULTS: In our previous study on the acute inhalational toxicity of BAC, bleeding from the nasal cavity was observed in all the rats after exposure to 50 mg/m3 BAC. Therefore, in this study, 20 mg/m3 was set as the highest exposure concentration, followed by 4 and 0.8 mg/m3 as the medium and low concentrations for 6 h/day and 14 days, respectively. After exposure, recovery periods of 2 and 4 weeks were provided. Additionally, alveolar lavage fluid was analyzed in males of the BAC-exposed groups at the end of exposure and 2 weeks after exposure to evaluate oxidative damage. In the T3 group exposed to BAC, deep breathing, hoarseness, and nasal discharge were observed along with a decline in feed intake and body weight, and nasal discharge was also observed in the T1 and T2 groups. ROS/RNS, IL-1ß, IL-6, and MIP-2 levels decreased in a concentration-dependent manner in the bronchoalveolar lavage fluid. Histopathological examination showed cellular changes in the nasal cavity and the lungs of the TI, T2, and T3 groups. CONCLUSIONS: As a result, it was confirmed that the target organs in the respiratory system were the nasal cavity and the lungs. The adverse effects were evaluated as reversible responses to oxidative damage. Furthermore, the no observed adverse effect level was found to be less than 0.8 mg/m3 and the lowest benchmark dose was 0.0031 mg/m3. Accordingly, the derived no-effect level of BAC was calculated as 0.000062 mg/m3.

Differences in nasal immunoglobulin A responses to influenza vaccine strains after live attenuated influenza vaccine (LAIV) immunization in children.

Different vaccine strains included in the live attenuated influenza vaccine (LAIV) have variable efficacy. The reasons for this are not clear and may include differences in immunogenicity. We report a Phase IV open-label study on the immunogenicity of a single dose of quadrivalent LAIV (Fluenz™ Tetra) in children during the 2015/16 season, to investigate the antibody responses to different strains. Eligible children were enrolled to receive LAIV; nasal samples were collected before and approximately 4 weeks after immunization. There was a significant increase in nasal immunoglobulin (Ig)A to the H3N2, B/Victoria lineage (B/Brisbane) and B/Yamagata lineage (B/Phuket) components, but not to the H1N1 component. The fold change in nasal IgA response was inversely proportional to the baseline nasal IgA titre for H1N1, H3N2 and B/Brisbane. We investigated possible associations that may explain baseline nasal IgA, including age and prior vaccination status, but found different patterns for different antigens, suggesting that the response is multi-factorial. Overall, we observed differences in immune responses to different viral strains included in the vaccine; the reasons for this require further investigation.

[The significance of eosinophils in the correlation of upper and lower airway inflammation in patients with chronic rhinitis].

Objective: To explore the predictor of lower airway inflammation among the index of nasal inflammation by investigating the expression and association of eosinophils (EOS) in the upper-lower airways and blood of patients with chronic rhinitis. Methods: A total of 162 patients with allergic rhinitis (AR), 117 patients with non-allergic rhinitis (NAR) and 104 controls were enrolled from June 2010 to December 2013 from General Hospital of Eastern Theater Command, People's Liberation Army. All subjects were required detailed medical history collection and nasal resistance measurement. Skin prick test (SPT), blood total immunoglobin E (tIgE) and blood EOS, nasal lavage and induced sputum EOS, nasal provocation and bronchial provocation test (NPT, BPT), nasal and forced exhaled nitric oxide (NNO, FeNO) were performed in all patients. One-way analysis of variance was used for comparison between groups. LSD t test or Mann-Whitney U test was used for comparison between the two groups. Pearson or Spearman related parameter test was used for correlation analysis. Results: The nasal lavage EOS, NNO, induced sputum EOS, FeNO, blood EOS and tIgE were higher in the AR group than that in the NAR group (3.70[1.20, 14.23]/200 HP vs 1.40[0.20, 3.40]/200 HP, 673.50[466.80, 936.00] ppb vs 455.80[248.10, 705.60] ppb, 2.97[0.00, 10.63]% vs 1.00[0.23, 2.00]%, (49.28±26.37)ppb vs (34.07±19.11)ppb, 4.00[2.00, 7.00]% vs 2.00[1.00, 5.00]%, 208.01[61.70, 387.50] IU/ml vs 43.30[19.00, 122.00] IU/ml, F or χ(2) value was 11.442, 19.440, 70.727, 69.449, 47.453, 46.525, respectively, all P<0.05). But there was no significant difference in nasal resistance, NPT and BPT between the two groups. Nasal lavage EOS in AR group and NAR group was correlated with induced sputum EOS, FeNO, tIgE and blood EOS (r value of AR group was 0.448, 0.202, 0.159, 0.321, r value of NAR group was 0.442, 0.268, 0.268, 0.334, respectively, all P<0.05), but not with BPT. After adjustment for gender, age, height and weight, nasal EOS was positively correlated with sputum EOS. Multiple linear regression analysis showed that nasal EOS, blood EOS and SPT were factors affecting sputum EOS levels. The optimal threshold for nasal EOS to determine induced sputum EOS was 3.30/200 HP by (receiver operating characteristic,ROC) analysis. Conclusion: The nasal EOS is correlated with multiple lower airway and systemic inflammatory markers, and is a risk factor for the induced sputum EOS, which can be used as an inflammation biomarker to predict the lower air inflammation.

Development of a Novel ex vivo Nasal Epithelial Cell Model Supporting Colonization With Human Nasal Microbiota.

The nasal mucosa provides first line defense against inhaled pathogens while creating a unique microenvironment for bacterial communities. Studying the impact of microbiota in the nasal cavity has been difficult due to limitations with current models including explant cultures, primary cells, or neoplastic cell lines. Most notably, none have been shown to support reproducible colonization by bacterial communities from human donors. Therefore, to conduct controlled studies of the human nasal ecosystem, we have developed a novel ex vivo mucosal model that supports bacterial colonization of a cultured host mucosa created by immortalized human nasal epithelial cells (NEC). For this model, immortalized NEC established from 5 male and 5 female donors were cultured with an air-interfaced, apical surface on a porous transwell membrane. NEC were grown from nasal turbinate tissues harvested from willed bodies or from discarded tissue collected during sinonasal procedures. Immortalized cells were evaluated through molecular verification of cell type, histological confirmation of tissue differentiation including formation of tight junctions, NEC multilayer viability, metabolism, physiology and imaging of the luminal surface by scanning electron microscopy. Results showed proper differentiation and multilayer formation at seven to 10 days after air interface that was maintained for up to 3 weeks. The optimized mucosal cultures created an environment necessary to sustain colonization by nasal microbiomes (NMBs) that were collected from healthy volunteers, cryogenically preserved and characterized with customized quantitative polymerase chain reaction (qPCR) arrays. Polymicrobial communities of nasal bacteria associated with healthy and inflamed states were consistently reproduced in matured NEC co-cultures by transplant of NMBs from multiple community types. The cultured NMBs were stable after an initial period of bacterial replication and equilibration. This novel ex vivo culture system is the first model that supports controlled cultivation of NMBs, allowing for lab-based causation studies and further experimentation to explore the complexities of host-microbe and microbe-microbe interactions.

Mucosal immunoglobulins protect the olfactory organ of teleost fish against parasitic infection.

The olfactory organ of vertebrates receives chemical cues present in the air or water and, at the same time, they are exposed to invading pathogens. Nasal-associated lymphoid tissue (NALT), which serves as a mucosal inductive site for humoral immune responses against antigen stimulation in mammals, is present also in teleosts. IgT in teleosts is responsible for similar functions to those carried out by IgA in mammals. Moreover, teleost NALT is known to contain B-cells and teleost nasal mucus contains immunoglobulins (Igs). Yet, whether nasal B cells and Igs respond to infection remains unknown. We hypothesized that water-borne parasites can invade the nasal cavity of fish and elicit local specific immune responses. To address this hypothesis, we developed a model of bath infection with the Ichthyophthirius multifiliis (Ich) parasite in rainbow trout, Oncorhynchus mykiss, an ancient bony fish, and investigated the nasal adaptive immune response against this parasite. Critically, we found that Ich parasites in water could reach the nasal cavity and successfully invade the nasal mucosa. Moreover, strong parasite-specific IgT responses were detected in the nasal mucus, and the accumulation of IgT+ B-cells was noted in the nasal epidermis after Ich infection. Strikingly, local IgT+ B-cell proliferation and parasite-specific IgT generation were found in the trout olfactory organ, providing new evidence that nasal-specific immune responses were induced locally by a parasitic challenge. Overall, our findings suggest that nasal mucosal adaptive immune responses are similar to those reported in other fish mucosal sites and that an antibody system with a dedicated mucosal Ig performs evolutionary conserved functions across vertebrate mucosal surfaces.

The Role of BPIFA1 in Upper Airway Microbial Infections and Correlated Diseases.

The mucosa is part of the first line of immune defense against pathogen exposure in humans and prevents viral and bacterial infection of the soft palate, lungs, uvula, and nasal cavity that comprise the ear-nose-throat (ENT) region. Bactericidal/permeability-increasing fold containing family A, member 1 (BPIFA1) is a secretory protein found in human upper aerodigestive tract mucosa. This innate material is secreted in mucosal fluid or found in submucosal tissue in the human soft palate, lung, uvula, and nasal cavity. BPIFA1 is a critical component of the innate immune response that prevents upper airway diseases. This review will provide a brief introduction of the roles of BPIFA1 in the upper airway (with a focus on the nasal cavity, sinus, and middle ear), specifically its history, identification, distribution in various human tissues, function, and diagnostic value in various upper airway infectious diseases.

Pure intravascular recurrence of CD5-positive diffuse large B-cell lymphoma primarily arising from the nasal cavities.

BACKGROUND: CD5-positive diffuse large B-cell lymphoma (DLBCL) and intravascular large B-cell lymphoma (IVL) are recognized as rare subsets of large B-cell lymphoma with poor prognosis. These two categories have similar clinicopathological features suggesting that they might overlap. CASE PRESENTATION: We present a case of a 72-year-old man with submental tumors. Positron emission tomography/computed tomography (PET/CT) showed tumors in the nasal and paranasal region and multiple submental and jugular swollen lymph nodes with abnormal uptake of 18F-fluorodeoxyglucose (FDG). Histology of biopsy from nasal tumors showed diffuse infiltration of large lymphoid cells, which showed positive expressions for CD20, CD79a, CD5 and negative for CD3 on immunohistochemistry. Thus, a CD5-positive DLBCL was diagnosed. After administration of 8 cycles of R-THPCOP (rituximab, pirarubicin, cyclophosphamide, vincristine and prednisolone), complete remission was achieved. Eight months after the first chemotherapy dose, local recurrence occurred. After salvage chemotherapy, nasal and paranasal tumors and lymph node swelling disappeared on PET/CT images, although the patient suffered from respiratory disturbance. A random skin biopsy revealed IVL, which was consistent with intravascular recurrence of CD5-positive DLBCL. Bone marrow smears showed hemophagocytosis. CONCLUSION: We present a rare case of primary CD5-positive DLBCL that relapsed as pure IVL after chemotherapy. Our case suggests that CD5-positive DLBCL is closely related to IVL.

The use of immunohistochemical methods in the study of morphofunctional features of the human paranasal sinuses: literature review.

OBJECTIVE: Introduction:Chronic inflammatory diseases of the mucous membrane of the nose, paranasal sinuses, and pharynx are the most widespread pathology of the upper airways. The thorough study of the features of the organization of local immune protection of the mucous membrane of the paranasal sinuses is crucial for the deep understanding of the causes of the onset and development of this and other pathologies of the paranasal sinuses, the choice of methods of diagnostics and treatment. Consequently, immunohistochemical studies are of great potential and have become preferable for great number of researchers. The aim: The paper was aimed at the analysis of the publications on the use of immunohistochemical methods in the study of the structural and functional features of the paranasal sinuses. PATIENTS AND METHODS: Materials and methods: The bibliosemantic method has been used during the study. Findings of the current research works on the use of immunohistochemical methods in the study of the paranasal sinuses have been analyzed. RESULTS: Review:The findings of the analysis shows that the use of immunohistochemical methods in the otorhinolaryngology is becoming more and more popular in the study of both morphofunctional features of the paranasal sinuses and in various experimental studies. CONCLUSION: Conclusion: The use of immunohistochemical methods in the study of the paranasal sinuses in both clinical otorhinolaryngology and theoretical morphology is relevant to date and is considered reasonable and perspective.