Guidance of clinical management for patients with tonsillar focal disease.

Tonsillar focal diseases (TFDs) are defined as "diseases caused by organic and/or functional damage in organs distant from tonsil, and the disease outcome is improved by tonsillectomy." Although several reports and reviews have shown the efficacy of tonsillectomy for TFDs, no guidelines for the clinical management of the diagnosis and treatment of TFDs have been reported. Therefore, the Society of Stomato-pharyngology established a committee to guide the clinical management of patients with TFDs, and the original guide was published in May 2023. This article summarizes the English version of the manuscript. We hope that the concept of TFDs will spread worldwide, and that one as many patients with TFDs will benefit from tonsillectomy.

Comprehensive Genetic Evaluation in Patients with Special Reference to Late-Onset Sensorineural Hearing Loss.

Hearing loss (HL) is a common and multi-complex etiological deficit that can occur at any age and can be caused by genetic variants, aging, toxic drugs, noise, injury, viral infection, and other factors. Recently, a high incidence of genetic etiologies in congenital HL has been reported, and the usefulness of genetic testing has been widely accepted in congenital-onset or early-onset HL. In contrast, there have been few comprehensive reports on the relationship between late-onset HL and genetic causes. In this study, we performed next-generation sequencing analysis for 91 HL patients mainly consisting of late-onset HL patients. As a result, we identified 23 possibly disease-causing variants from 29 probands, affording a diagnostic rate for this study of 31.9%. The highest diagnostic rate was observed in the congenital/early-onset group (42.9%), followed by the juvenile/young adult-onset group (31.7%), and the middle-aged/aged-onset group (21.4%). The diagnostic ratio decreased with age; however, genetic etiologies were involved to a considerable degree even in late-onset HL. In particular, the responsible gene variants were found in 19 (55.9%) of 34 patients with a familial history and progressive HL. Therefore, this phenotype is considered to be a good candidate for genetic evaluation based on this diagnostic panel.

Impact of Phosphorylcholine Expression on the Adherence and Invasion of Streptococcus pyogenes to Epithelial Cells.

Phosphorylcholine (PC) is a structural component of various pathogens and is involved in bacterial adhesion via the platelet-activating factor receptor (PAF-R). In this study, we investigated how PC expression affects cell adhesion and invasion of Streptococcus pyogenes (S. pyogenes). Eight clinical strains of S. pyogenes were cultured, and PC expression was measured using fluorescence-activated cell sorting. Bacterial adherence and invasion were examined using Detroit 562 cells. An anti-PC-specific monoclonal antibody (TEPC-15) was used to inhibit bacterial PC, and a PAF-R antagonist (ABT-491) was used to inhibit cellular PAF-R. The emm gene was amplified by the polymerase chain reaction with the standard primers. The level of PC expressed on the S. pyogenes surfaces differed in each strain and differed even in the same emm genotype. Adherence assay experiments showed a significant negative correlation between TEPC-15 and ABT-491 inhibitory effects and PC expression in S. pyogenes. Similarly, intracellular invasion assay experiments showed a significant negative correlation between TEPC-15 and ABT-491 inhibitory effects and PC expression in S. pyogenes. This study suggests that S. pyogenes is involved in cell adhesion and invasion by PC.

Efficacy of endoscopic ultrasonography in evaluating tumor thickness in patients with superficial pharyngeal carcinoma: A pilot study.

OBJECTIVES: A histopathological tumor thickness of ≥1000 µm has been reported as one of many risk factors for recurrent lymph node metastasis in superficial pharyngeal cancer (SPC). However, methods for assessing this risk factor preoperatively have not yet been established. Hence, the current study aimed to evaluate the efficacy of endoscopic ultrasonography (EUS) in measuring tumor thickness preoperatively in patients with SPC. METHODS: This single-center retrospective study included 44 consecutive patients with 47 lesions who underwent endoscopic submucosal dissection (ESD). Prior to surgery, EUS examination was performed while under general anesthesia. Further, microvascular irregularity in the target lesion was evaluated using the Japan Esophageal Society (JES) magnification endoscopic classification system. RESULTS: A significant correlation was noted between histopathological and EUS tumor thickness (Spearman's correlation r == 0.879, p < 0.001). In tumors ≥1000 µm thick on histopathology, the cutoff value for EUS tumor thickness was 2.6 mm, and the following values were obtained: sensitivity, 100%; specificity, 81.8%; positive predictive value (PPV), 70%; negative predictive value (NPV), 100%; and accuracy, 87.2%. In B2 lesions ≥1000-µm thick, the following values were obtained: sensitivity, 85.7%; specificity, 90.9%; PPV, 80%; NPV, 93.8%; and accuracy, 89.4%. The diagnostic accuracy rate of combined EUS and the JES magnifying endoscopic classification system was 95.7%. CONCLUSIONS: Tumor thickness assessed using EUS was effective in diagnosing histopathological tumor thickness of ≥1000 µm. The combined use of EUS and the JES magnifying endoscopic classification system may be useful for assessing preoperative risk factors for lymph node metastasis in SPC.

Utility of the Modified and High-Sensitivity Modified Glasgow Prognostic Scores for Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To determine whether the modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) could predict outcomes among patients with hypopharyngeal squamous cell carcinoma (HSCC). STUDY DESIGN: Retrospective cohort study. SETTING: Affiliated university hospital. METHODS: We reviewed the records of 115 patients with histologically confirmed HSCC between March 2007 and December 2019. Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS). RESULTS: The 5-year OS rates were 84.0% for the mGPS0 group, 47.8% for the mGPS1 group, and 17.9% for the mGPS2 group (P < .0001), while the 5-year OS rates were 86.7% for the HS-mGPS0 group, 69.0% for the HS-mGPS1 group, and 22.2% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with OS in the univariate analyses, although only the HS-mGPS was independently associated with OS (hazard ratio, 2.68 [95% CI, 1.19-6.05]; P < .05). The 5-year DFS rates were 75.8% for the mGPS0 group, 53.0% for the mGPS1 group, and 13.8% for the mGPS2 group (P < .001), while the 5-year DFS rates were 79.8% for the HS-mGPS0 group, 56.8% for the HS-mGPS1 group, and 11.6% for the HS-mGPS2 group (P < .001). The mGPS and HS-mGPS were both associated with DFS in the univariate analyses, although only the HS-mGPS was independently associated with DFS (hazard ratio, 2.35 [95% CI, 1.03-5.37]; P < .05). CONCLUSION: Our study suggests that the HS-mGPS is useful as prognostic factor in HSCC.

Utility of the High-Sensitivity Modified Glasgow Prognostic Scores for Oropharyngeal Carcinoma.

OBJECTIVE: There is increasing evidence that the high-sensitivity modified Glasgow prognostic scores are inflammatory indices that can predict survival for many cancer types. However, there is limited information regarding their prognostic values in cases of head and neck cancer. This study aimed to evaluate whether the high-sensitivity modified Glasgow prognostic scores could predict outcomes among patients with oropharyngeal squamous cell carcinoma (OPC). STUDY DESIGN: Retrospective study. SETTING: University hospital. METHODS: We reviewed the records of 106 patients with histologically confirmed OPC between March 2009 and June 2020. The high-sensitivity modified Glasgow prognostic scores were calculated as 0 (C-reactive protein [CRP] concentration: ≤0.3 mg/dL), 1 (CRP concentration >0.3 mg/dL and albumin concentration ≥3.5 mg/dL), or 2 (CRP concentration >0.3 mg/dL and albumin concentration <3.5 mg/dL). Univariate and multivariable Cox proportional hazard analyses were performed for overall survival (OS) and disease-free survival (DFS). RESULTS: Forty-four of these patients had human papillomavirus (HPV)-positive OPC, and 62 had HPV-negative OPC, and these populations were analyzed separately. The high-sensitivity modified Glasgow prognostic score was significantly associated with age, performance status, and HPV. On univariate analysis, high-sensitivity modified Glasgow prognostic score showed associations with OS and DFS in both subpopulations. Moreover, on multivariable analysis, the high-sensitivity modified Glasgow prognostic score showed associations with OS and DFS in both subpopulations. Poor performance status predicted OS in both subpopulations. CONCLUSION: We conclude that the high-sensitivity modified Glasgow prognostic score is useful as an independent prognostic factor in OPC.

Effectiveness of antibacterial agents against cell-invading bacteria such as Streptococcus pyogenes and Haemophilus influenzae.

BACKGROUND: Recurrent tonsillitis is one of the most common otolaryngological disorders caused by cell-invading bacteria, such as Streptococcus pyogenes (S. pyogenes) and Haemophilus influenzae. The aim of this study was to investigate the effect of antibacterial agents against cell-invading bacteria. METHODS: The intracellular invasion of Detroit 562 cells by five strains of nontypeable Haemophilus influenzae (NTHi) and four strains of S. pyogenes was investigated. The antibacterial agents used were garenoxacin (GRNX), clarithromycin (CAM), amoxicillin (AMPC), cefditoren pivoxil (CDTR-PI), and levofloxacin (LVFX). RESULTS: Both NTHi and S. pyogenes fully invaded Detroit 562 cells in 6 h and were less sensitive to CAM. GRNX, CAM, and LVFX were effective against bacteria invading the cells, but AMPC and CDTR-PI were not effective. GRNX was the most effective. CONCLUSION: GRNX was the most effective agent against bacteria invading cells.

Three cases of non-occlusive mesenteric ischemia that developed after head and neck cancer therapy.

Non-occlusive mesenteric ischemia (NOMI) causes intestinal necrosis due to irreversible ischemia of the intestinal tract despite the absence of organic obstruction in the mesenteric blood vessels. The disease has extremely poor prognosis. We report three cases of NOMI hypothesized to have developed after head and neck cancer therapy; thus, we report these cases considering the available literature. Case 1: A 74-year-old man with T2N0M0 stage Ⅱ oropharyngeal carcinoma complained of abdominal pain 5 days after chemoradiotherapy. The patient was diagnosed with NOMI, and an emergency surgery was performed. Case 2: A 69-year-old man with T2N2bM0 stage IVA hypopharyngeal carcinoma complained of abdominal pain during TPF chemotherapy. The patient was diagnosed with NOMI, and he died on the same day. Case 3: A 82-year-old man with T2N2bM0 stage IVA hypopharyngeal carcinoma complained of abdominal pain with reduced level of consciousness, 5 days after total laryngopharyngectomy. The patient was diagnosed with NOMI, and an emergency surgery was performed on the same day. We therefore suggest that ENT physicians must be aware of NOMI as a complication that can develop after head and neck cancer therapy.

Inhibitory effects of 2-methacryloyloxyethyl phosphorylcholine polymer on the adherence of bacteria causing upper respiratory tract infection.

OBJECTIVE: We aimed to investigate the inhibitory effect of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer on the adherence of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi) in vitro and in vivo. MATERIALS AND METHODS: Phosphorylcholine (PC) expression of 21 strains each of Spn and NTHi was evaluated using fluorescence-activated cell sorting; the adherence of bacteria to Detroit 562 cells and to the nasal mucosa of BALB/c mice was determined. MPC polymer-mediated inhibitory effects were compared with PC-keyhole limpet hemocyanin (PC-KLH)-mediated inhibitory effects. RESULTS: In vitro experiments showed that pretreatment with MPC polymer markedly inhibited the adherence of Spn and NTHi in a concentration dose-dependent manner independently of PC expression. No correlation was observed between PC expression and MPC polymer-mediated inhibitory effects. Contrarily, there was a significant negative correlation between PC-KLH-mediated inhibitory effects and PC expression in Spn and NTHi. The same results were obtained via in vivo experiments. The MPC polymer did not affect the histology of the nasal mucosa. CONCLUSIONS: MPC polymer might be effective to reduce the occurrence of upper respiratory tract infection caused by Spn and NTHi and could be applied for the development of local treatments, such as topical gargles and nebulizer medications.

Unilateral arytenoid swelling in acute epiglottitis suggests the presence of peritonsillar abscess.

OBJECTIVE: To investigate the incidence of acute epiglottitis (AE) and the clinical features of patients with AE complicated by peritonsillar abscess (PTA), considering that PTA, especially inferior-type PTA, is often a comorbidity of AE. METHODS: We retrospectively reviewed the medical records of patients who were diagnosed as having AE by otolaryngologists and referred to our hospital between January 2009 and December 2017. All the patients underwent laryngeal endoscopy and contrast-enhanced computed tomography (CT) for examination of the severity of AE and its complications by other infections, including PTA. The clinical characteristics of patients with PTA were compared with those of patients without PTA. RESULTS: A total of 139 patients were enrolled, of whom 21 (15%) were found to have PTA. Among the 21 patients, only one had a superior-type PTA and the others had an inferior-type PTA. The patients with complicated AE by an inferior Cap-type PTA frequently showed unilateral arytenoid swelling. CONCLUSION: PTA is a comorbidity of AE, and unilateral arytenoid swelling is considered to suggest the presence of inferior-type PTA.

Impacts of Inflammation-Based Prognostic Scores on Survival in Patients With Hypopharyngeal Squamous Cell Carcinoma.

OBJECTIVE: To investigate the predictive accuracies of the modified Glasgow Prognostic Score (mGPS), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) as prognostic factors for patients with hypopharyngeal squamous cell carcinoma (HSCC). STUDY DESIGN: Retrospective study. SETTING: University hospital. METHODS: The records of 106 patients who were histologically diagnosed with HSCC between January 2007 and December 2017 were reviewed. mGPS, NLR, and PLR were analyzed; univariate and multivariate analyses were performed to evaluate the prognosis of overall survival (OS). RESULTS: The overall 5-year survival rates of patients with mGPS0, mGPS1, and mGPS2 were 82.0%, 41.9%, and 13.5%, respectively. The overall 5-year survival rates of patients with low and high NLRs and with low and high PLRs were 83.8%, 46.2%, 57.0%, and 59.1%, respectively. mGPS (P < .001) and NLR (P < .05) were independently associated with OS, whereas PLR was not. For stage IV HSCC, only mGPS was independently associated with OS (P = .004). CONCLUSION: mGPS is an excellent prognostic factor for patients with HSCC.

The usefulness of abscess tonsillectomy followed by intraoral drainage for parapharyngeal abscess concomitant with peritonsillar abscess in the elderly.

Parapharyngeal abscess (PPA) may cause life-threatening complications and peritonsillar abscess (PTA) and tonsillitis frequently precede PPA. The optimal management of PPA caused by PTA has been the subject of debate with respect to the surgical approach. We present three cases of PPA concomitant with PTA in elderly patients. In two cases, the abscesses in parapharyngeal space were drained by abscess tonsillectomy followed by intraoral incision of the tonsillar bed. On the other hand, the third case did not undergo abscess tonsillectomy because of his refusal of surgery and needed extraoral drainage after the aggravation of PPA. Based on the experience of those three cases, it was suggested that abscess tonsillectomy followed by intraoral incision of the tonsillar bed might be a useful surgical approach for the drainage of PPA concomitant with PTA, especially in elderly patients.

Squamous cell carcinoma at sites of old maxillary fractures.

Malignancies have been reported to occasionally arise in scar tissue following injury. One hypothesis involves prolonged overactivation of tissue repair systems due to chronic inflammation and irritation, although the pathogenesis of cancers occurring in scars is not fully understood. We describe here two cases with a history of maxillary fracture at the site where squamous cell carcinoma (SCC) subsequently developed. The first patient developed SCC 7 years after right maxillary fractures resulting from a traffic accident. He underwent chemoradiotherapy (70 Gy in 35 fractions) and maintained complete response (CR) for 10 months. The second patient developed SCC 3 years after sustaining right maxillary fractures in an ice hockey game. Radiotherapy and total maxillectomy were performed, but local recurrence arose and he has since been receiving chemotherapy.

Phosphorylcholine intranasal immunization with a 13-valent pneumococcal conjugate vaccine can boost immune response against Streptococcus pneumoniae.

OBJECTIVE: This study aimed to investigate whether systemic immunization with a 13-valent pneumococcal conjugate vaccine (PCV13) followed by intranasal (IN) immunization with phosphorylcholine (PC) can boost immune response against Streptococcus pneumoniae. MATERIALS AND METHODS: Two weeks after the intraperitoneal (IP) injection of PCV13, mice were divided into two groups (mice requiring another IP injection of PCV13 and mice requiring PC-keyhole limpet hemocyanin IN immunization in combination with cholera toxin as a mucosal adjuvant) to compare the magnitude of systemic and mucosal immune responses against S. pneumoniae and PC. RESULTS: Serum immunoglobulin (Ig) G antibody titer against the vaccine strains of S. pneumoniae was similar between the PCV13 systemic immunization group and PC IN immunization group, while the serum IgG antibody titer against PC was significantly higher in the PC IN immunization group. PC-specific IgA antibody titer in the nasal lavage and PC-specific IgA-producing cell number in the nasal mucosa were also significantly higher in the PC IN immunization group. Induction of PC-specific IgA in the PC IN immunization group enhanced the clearance of bacteria from the middle ear. CONCLUSION: Additional IN immunization with PC after PCV13 immunization, which is currently conducted under a periodic vaccination program, can produce a booster effect comparable to that achieved by additional systemic immunization as well as PC-specific mucosal immune response, thereby providing protection against S. pneumoniae serotypes not contained in PCV13.

Role of Phosphorylcholine-Specific Immunoglobulin M in Acute Upper Respiratory Tract Infections.

OBJECTIVES: The aim of this study was to clarify the role of serum phosphorylcholine (PC)-specific immunoglobulin M (IgM) as a natural antibody against infectious diseases. METHODS: The relationship between serum PC-specific IgM level and C-reactive protein level or white blood cell counts was examined in patients with severe upper respiratory tract infections (ie, acute epiglottitis and peritonsillar abscess). RESULTS: PC-specific IgM level was significantly negatively correlated with C-reactive protein level and white blood cell count. In addition, C-reactive protein level and white blood cell count was significantly lower in women than in men, whereas PC-specific IgM level was significantly higher in women. CONCLUSIONS: PC-specific IgM is suggested to have protective and suppressive effects against the progression of infectious and inflammatory reactions. Higher levels of PC-specific IgM in women might be one of the reasons why the incidence and severity of acute epiglottitis and peritonsillar abscess are lower in women.

Role of phosphorylcholine in Streptococcus pneumoniae and nontypeable Haemophilus influenzae adherence to epithelial cells.

OBJECTIVE: Phosphorylcholine (PC) is a structural component of Streptococcus pneumoniae (Spn) and nontypeable Haemophilus influenzae (NTHi), and is known to be associated with adherence through the platelet activating factor receptor (PAF-R). Furthermore, high PC expression is considered to be involved in Spn and NTHi virulence. In this study, we examined the influence of PC expression on the adherence of Spn and NTHi to epithelial cells in order to clarify the potential effectiveness of a vaccine targeting PC. METHODS: Twenty-seven strains of Spn and twenty-two strains of NTHi were used, cultured overnight, and PC expression was evaluated by fluorescence activated cell sorting; the strains were divided into two groups: PC low expression (PC-low) and PC high expression (PC-high) groups. Bacterial adherence was then examined using Detroit 562 cells and BALB/c mice. Bacterial invasion was then examined in Detroit 562 cells. RESULTS: The adherence of Spn and NTHi and invasion of NTHi in the PC-high group was significantly reduced by pretreatment with a monoclonal anti-PC antibody (TEPC-15), PAF-R antagonist (ABT-491), and PC-keyhole limpet hemocyanin (PC-KLH). However, such findings were not observed in the PC-low group. CONCLUSION: The present study suggests that PC is involved in the mucosal adhesion of Spn and NTHi, and the mucosal invasion of NTHi with PC-high strains, but not PC-low strains. These results suggest that a PC-targeting mucosal vaccine only affects PC-high Spn and NTHi strains and does not disturb commensal bacterial flora in the upper respiratory tract, which comprises nonpathogenic PC-low bacteria.

The role of phosphorylcholine-specific immune responses in the tonsils and peripheral blood on IgA nephropathy.

BACKGROUND: Tonsillectomy combined with steroid pulse therapy was reported to be effective for patients with IgA nephropathy. However, the mechanisms of the effect of tonsillectomy on IgA nephropathy are unknown. AIM: The aim of this study was to investigate the involvement of the phosphorylcholine (PC)-specific immune response in the tonsils and peripheral blood of patients with IgA nephropathy. MATERIAL AND METHODS: Tonsillar lymphocytes were isolated and the number of PC-specific immunoglobulin-producing cells was measured. Additionally, serum PC-specific immunoglobulin levels were quantified and compared with laboratory findings. RESULTS: The number of PC-specific IgA-producing cells was increased in the tonsils of patients with IgA nephropathy. The value was significantly elevated in the group with a higher risk of initiating dialysis. In contrast, PC-specific IgM levels in the serum were significantly elevated in the group with a lower risk of initiating dialysis. CONCLUSIONS AND SIGNIFICANCE: PC-specific immune responses in the tonsils and peripheral blood may be related to the pathological mechanism and progression of IgA nephropathy.

Intranasal immunization with phosphorylcholine suppresses allergic rhinitis in mice.

OBJECTIVES/HYPOTHESIS: Intranasal immunization with phosphorylcholine (PC) is known to reduce immunoglobulin (Ig)E production. However, its effects on the occurrence of allergic rhinitis (AR) are unknown. This study was performed to evaluate the effects of PC-keyhole limpet hemocyanin (PC-KLH) and to examine the effects on the occurrence of AR in a murine model of AR. STUDY DESIGN: In vivo study using an animal model. METHODS: Forty-five female BALB/c mice were divided into three groups; those pretreated with intranasal administration of PC-KLH followed by intraperitoneal sensitization and nasal challenge with ovalbumin (OVA) (group A), those untreated with PC-KLH followed by sensitization and nasal challenge with OVA (group B), and those untreated with PC-KLH or OVA as controls (group C). Nasal symptoms, allergic inflammation in the nasal mucosa, OVA specific IgE production, and cytokine profile were compared among those three groups. Dendritic cells (DCs) were isolated from splenic cells and PC-KLH-stimulated interleukin (IL)-12p40 production was measured. RESULTS: The mice pretreated with PC-KLH showed lower allergic nasal symptoms and inflammation compared to untreated mice. The levels of total IgE and OVA-specific IgE in serum, and IL-4 production by nasal and splenic CD4+ T cells were significantly reduced by PC-KLH pretreatment. Furthermore, IL-12p40 production by DCs was induced by PC-KLH in a dose-dependent manner. CONCLUSIONS: Intranasal administration of PC-KLH suppressed allergic inflammation in nasal mucosa and antigen-specific IgE production by downregulating Th2-type immune response. Intranasal immunization with PC might be useful to prevent AR and upper airway bacterial infection. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E234-E240, 2018.

Transcutaneous immunization with pneumococcal surface protein A in mice.

OBJECTIVE: Pneumococcal infection caused by Streptococcus pneumoniae is a major upper respiratory tract disease that causes severe illness and mortality. Therefore, it is important to develop safe and effective vaccines to prevent pneumococcal infections. The goal of the study was to investigate the effectiveness of transcutaneous immunization (TCI) for induction of pneumococcal surface protein A (PspA) responses in the upper respiratory tract. METHODS: C57BL/6 mice were transcutaneously immunized with 1 µg of PspA and 2 µg of cholera toxin (CT) six times at weekly intervals and compared with transcutaneously treated controls (PBS alone/PspA alone/CT alone). Two weeks after the final immunization, nasal washes (NWs), saliva, and plasma samples were collected and subjected to a PspA-specific ELISA. Three weeks after the final immunization, mice were challenged with S. pneumoniae strain EF3030, and the numbers of CFUs in NWs and nasal passages (NPs) were determined. RESULTS: Higher levels of PspA-specific IgM, IgG, and IgA Abs were noted in plasma of TCI with PspA plus CT compared with controls. Transcutaneous immunization mice also had significantly increased PspA-specific S-IgA Ab responses in NWs and saliva and, importantly, showed significantly lower numbers of bacteria CFUs in NWs and NPs compared with controls. CONCLUSION: These results show that TCI with PspA plus CT induces antigen-specific mucosal and systemic immune responses. This suggests that this method is an effective mucosal immunization strategy for induction of protective pneumococcal-specific Ab responses in blockade of S. pneumoniae colonization of the nasal cavity. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:E91-E96, 2018.

Mucosal and systemic immune response to sublingual or intranasal immunization with phosphorylcholine.

OBJECTIVE: Phosphorylcholine (PC) is a structural component of a wide variety of pathogens including Streptococcus pneumoniae and Haemophilus influenzae. Here, the immune response in mice to PC immunization via the sublingual (SL) route versus the intranasal (IN) route was investigated in terms of efficacy and safety. METHODS: BALB/c mice were immunized with PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT) or CT alone via the IN or SL route. The immune response generated was studied in terms of PC-specific antibody titers, interferon (IFN)-γ and interleukin (IL)-4 production by CD4+ T cells, and cross-reactivity of PC-specific immunoglobulin (Ig)-A antibodies in nasal washes against S. pneumoniae and non-typeable H. influenzae. RESULTS: SL and IN immunization with PC-KLH plus CT resulted in a marked increase in the levels of PC-specific, mucosal IgA and serum IgM, IgG, and IgA antibodies. Additionally, SL immunization elicited significantly higher levels of PC-specific IgG2a subclass antibodies and IFN-γ in serum. On the other hand, IN immunization with CT alone remarkably increased the total IgE level in serum compared with SL and IN immunization with PC-KLH plus CT. PC-specific IgA antibodies in nasal wash samples reacted to most strains of S. pneumoniae and non-typeable H. influenzae. CONCLUSION: SL immunization is as effective as IN immunization to induce PC-specific immune responses and more effective than IN immunization to reduce the production of IgE and to prevent the sensitization to allergen causing type I allergy.