New evidence of connections between increased O-GlcNAcylation and inflammasome in the oral mucosa of patients with oral lichen planus.

Oral lichen planus (OLP) is considered a chronic inflammatory immune-mediated disease of the oral mucosa. Immunopathogenesis of OLP is thought to be associated with cell-mediated immune dysregulation. O-GlcNAcylation is a form of reversible glycosylation. It has been demonstrated that O-GlcNAcylation promoted nuclear factor kappa B (NF-κB) signalling. Activation of NF-кB can induce expression of nucleotide-binding domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, which is a large intracellular multi-protein complex involving an immune response. Dysregulated expression of the NLRP3 inflammasome was reported to be associated with autoinflammatory diseases. No integrative studies between O-GlcNAcylation and NLRP3 inflammasome in OLP patients have been reported. The present study aimed to determine the immunohistochemical expression of O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome in oral mucosae of OLP patients. Oral tissue samples were collected from 30 OLP patients and 30 healthy individuals. Immunohistochemical staining and analyses of immunostaining scores were performed to evaluate expression of O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome. According to observations in this study, significantly higher levels of O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome were demonstrated in OLP patients compared with control subjects (P < 0·001). Positive correlations among O-GlcNAcylation, NF-κB signalling molecules and NLRP3 inflammasome were also observed in OLP samples (P < 0·01). In conclusion, the present study provides supportive evidence that increased O-GlcNAcylation is associated with increased expression of NLRP3 inflammasome via the NF-κB signalling pathway. These findings provide a new perspective on immunopathogenesis of OLP in relation to autoinflammation.

Salivary Lysozyme in Relation to Dental Caries among Thai Preschoolers.

AIM: The objective of this study was to analyze salivary lysozyme levels and activities in Thai preschoolers with different dental caries status. STUDY DESIGN: Unstimulated saliva samples were collected from 64 preschoolers, divided into a caries free group (n = 32) and a severe early childhood caries (S-ECC) group (n = 32). RESULTS: Both groups were similar regarding gender, age, dental caries status, salivary flow rate, and salivary protein concentrations. No differences were also in the caregivers' characteristics, oral health behaviors, and feeding habits. Only professional fluoride application was less frequently found in the S-ECC group (p < 0.03). Western blotting and lysoplate assays revealed that salivary lysozyme levels and activities were significantly increased in the S-ECC group compared with the caries free group (p< 0.001; p = 0.008, respectively). CONCLUSION: The up-regulated expression of salivary lysozyme and the increased lysozyme activity in S-ECC preschoolers suggests a possible connection between salivary lysozyme and oral immunity in response to early childhood dental caries.

Determinación de IgA salival contra la gp120 en pacientes VIH+ y VIH- / Determination of salivary IgA against gp120 in HIV+ and HIV- patients

La producción de inmunoglobulina A (sIgA) es uno de los mecanismos a través de los cuales el sistema inmune humoral protege a las superficies mucosas, inhibiendo la adherencia de patógenos y neutralizando la acción de los virus. Estudios realizados con individuos VIH+ han demostrado que la IgA se une a las glicoproteínas de la envoltura, gp120 ygp41, del virus VIH-1. Objetivo: el propósito de este trabajo fue detectar los niveles de IgA salival contra 50 péptidos que representan la gp120 de la envoltura del virus VIH-1 y están constituidos por secuencias de 20 aminoácidos. Materiales y métodos: se utilizó la técnica de inmunoensayo enzimático (ELISA) con saliva total no estimulada de 24 sujetos, que fueron divididos en 3 grupos: 9 VIH+CD4>200 mm3; 10 VIH+CD4<200 mm3 y 5 VIH-. Los péptidos utilizados cubrieron el espectro de 510 aminoácidos de la gp120. Resultados: los resultados demostraron que los niveles de IgA específica fueron significativamente mayores (p=0.0001) en el grupo VIH+ que en el grupo VIH-. No se observaron diferencias significativas entre los grupos VIH+CD4>200 mm3 y VIH+CD4<200 mm3. No se observó correlación significativa entre el contaje CD+ y las respuestas de IgA. Los péptidos con mayor número de respuestas en el grupo VIH+ correspondieron a las regiones C1, V2 y C3. Conclusiones: los niveles de IgA salival observados en este estudio no mostraron variabilidad en relación con el contaje de células CD4+ y los péptidos que provocaron mayores respuestas de anticuerpos correspondieron a regiones con poca variabilidad sobre la cubierta del virus

Salivary immunoglobulin A antibodies to gp41 in human immunodeficiency virus-seropositive patients: lack of correlation with disease progression.

Mucous membranes are the main route of transmission of human immunodeficiency virus (HIV). Interestingly, some viral inhibitory activities have been found in saliva. The purpose of this study was to determine the level of salivary immunoglobulin A (IgA) antibodies to gp41 in HIV+ patients at various disease stages to identify whether gp41 was able to induce vigorous humoral responses. Unstimulated saliva samples were obtained from three groups of subjects (n=37): group A (HIV-), group B (HIV+, CD4+ <200/mm3), and group C (HIV+, CD4+ >200/mm3). IgA antibody levels to purified gp41 were determined by enzyme-linked immunosorbent assay (ELISA). Western blot analyses were performed using HIV+ saliva to confirm IgA reactivity to gp41. ELISA demonstrated that HIV+ subjects had higher IgA antibody to gp41 than HIV- individuals. No significant differences were noted between HIV+, CD4+ <200/mm3 and CD4+ >200/mm3 subjects. High (81.25%) IgA reactivity to gp41 was demonstrated by Western blotting of saliva from all HIV+ individuals. In conclusion, gp41 responses are important in the HIV disease process, as indicated by the high IgA levels and gp41 reactivity in saliva of HIV+ patients.

Oral lichen planus: an immunohistochemical study of heat shock proteins (HSPs) and cytokeratins (CKs) and a unifying hypothesis of pathogenesis.

The expression of heat shock proteins HSP60 and HSP70 and cytokeratins CK1/10 and CK7/18 were compared in epithelium of oral lichen planus (OLP) lesions and oral fibromas using an avidin-biotin-peroxidase complex (ABC) immunohistochemical method. An immunostaining intensity distribution (IID) index was developed to assess staining intensity and the proportion of positively stained cells in different layers of the epithelium. The expression of HSP60 in the basal layer was significantly higher in OLP than in fibromas. No difference in HSP70 expression was evident between OLP and fibromas. The expression of CK1/10 in the epithelial basal and suprabasal layers was significantly higher in OLP than in fibromas. There was no demonstrable staining for CK7/18 in either OLP or fibromas. A significant correlation was evident between the expression of HSP60 and CK1/10 in the basal epithelial cells in OLP. The findings support a role for HSP60 in the pathogenesis of OLP. A unifying hypothesis of the pathogenesis of OLP, involving two sequential immune reactions, is proposed.