Application of phosphorylcholine derivative as mucosal adjuvant enhancing mucosal immune responses in the upper respiratory tract.

OBJECTIVE: A phosphorylcholine (PC)-derivative with high binding ability (PCDB) was intranasally administered to mice with ovalbumin (OVA), and immune responses were investigated to determine whether PCDB has antigenicity and adjuvanticity. METHODS: BALB/c mice were intranasally immunized with PCDB coupled with OVA, unbound PCDB plus OVA, cholera toxin (CT) plus OVA, OVA alone, and PCDB alone. Then, the production of OVA- and PC-specific antibodies in external secretions and serum, and the secretion of cytokines such as IL-4 and IFN-γ from splenic mononuclear cells by stimulation with PCDB and OVA were examined. Furthermore, the secretion of IL-12p40 from CD11c+ cells following stimulation with PCDB was observed to clarify the adjuvant effect of PCDB through TLR4. RESULTS: Intranasal immunization with PCDB plus OVA increased OVA- and PC-specific IgA in external secretions and OVA- and PC-specific antibodies in the serum. The analysis of IgG subclasses specific to OVA and PC showed a higher production of IgG1 than IgG2, and the secretion of both IL-4 and IFN-γ was enhanced. However, IL-12p40 secretion from CD11c+ cells was increased and OVA-specific IgE production was not promoted by PCDB stimulation. CONCLUSION: Intranasal administration of the protein antigen with PCDB enhanced immune responses specific to the mixed antigen and PC. Although PCDB acted to bias the immune response toward the Th2-type, antigen-specific IgE production did not increase. These findings suggest that PCDB has the potential to be a mucosal vaccine with both adjuvanticity and antigenicity without causing side effects due to type I allergy.

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.

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.

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.

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.

Transcutaneous immunization in auricle skin induces antigen-specific mucosal and systemic immune responses in BALB/c mice.

OBJECTIVE: Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on skin. Phosphorylcholine (PC) is a structural component of a variety of pathogens, and anti-PC immune responses protect mice against invasive bacterial diseases. The purpose of the study was to examine the effect of TCI using PC in back skin or auricle skin in BALB/c mice. METHODS: TCI was performed in BALB/c mice in back skin or auricle skin using PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Inoculations were given once each week for six consecutive weeks. Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA. IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-γ levels were also measured by ELISA. RESULTS: Serum IgG after TCI in auricle skin was significantly higher than after TCI in back skin and in controls. Secretory IgA antibodies after TCI in auricle skin were also significantly higher than after TCI in back skin and in controls in nasal, BALF, vaginal and fecal samples. PC-specific IgG1 and IgG2a were significantly higher after TCI in auricle skin compared to controls and compared to TCI in back skin. IgG1 was significantly higher than IgG2a after TCI in auricle skin. Production of IFN-γ, IL-4 and IL-10 from CD4+ cells was significantly higher after TCI in auricle skin than after TCI in back skin and in controls, whereas IL-5, IL-12 and IL-13 were not detected in any mice. CONCLUSION: These results suggest that TCI in auricle skin using PC plus CT in BALB/c mice is a simple approach for induction of systemic and mucosal immune responses that are shifted in the Th2 direction.