RESUMO
A relationship between IgA nephropathy (IgAN) and bacterial infection has been suspected. As IgAN is a chronic disease, bacteria that could cause chronic infection in oral areas might be pathogenetic bacteria candidates. Oral bacterial species related to dental caries and periodontitis should be candidates because these bacteria are well known to be pathogenic in chronic dental disease. Recently, several reports have indicated that collagen-binding protein (cnm)-(+) Streptococcs mutans is relate to the incidence of IgAN and the progression of IgAN. Among periodontal bacteria, Treponema denticola, Porphyromonas gingivalis and Campylobacte rectus were found to be related to the incidence of IgAN. These bacteria can cause IgAN-like histological findings in animal models. While the connection between oral bacterial infection, such as infection with S. mutans and periodontal bacteria, and the incidence of IgAN remains unclear, these bacterial infections might cause aberrantly glycosylated IgA1 in nasopharynx-associated lymphoid tissue, which has been reported to cause IgA deposition in mesangial areas in glomeruli, probably through the alteration of microRNAs related to the expression of glycosylation enzymes. The roles of other factors related to the incidence and progression of IgA, such as genes and cigarette smoking, can also be explained from the perspective of the relationship between these factors and oral bacteria. This review summarizes the relationship between IgAN and oral bacteria, such as cnm-(+) S. mutans and periodontal bacteria.
Assuntos
Infecções Bacterianas/complicações , Infecções Bacterianas/microbiologia , Cárie Dentária/complicações , Cárie Dentária/microbiologia , Glomerulonefrite por IGA/etiologia , Glomerulonefrite por IGA/metabolismo , Periodontite/complicações , Periodontite/microbiologia , Animais , Biomarcadores , Gerenciamento Clínico , Modelos Animais de Doenças , Suscetibilidade a Doenças , Regulação da Expressão Gênica , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/terapia , Humanos , Imunoglobulina A/imunologia , Imuno-Histoquímica , Linfócitos Intraepiteliais/imunologia , Linfócitos Intraepiteliais/metabolismo , Microbiota , Boca , Fatores de RiscoRESUMO
BACKGROUND: IgA nephropathy (IgAN) is one of the most frequently occurring types of chronic glomerulonephritis. Previous analyses have revealed that a major pathogen of dental caries, Streptococcus mutans [which expresses collagen-binding protein (Cnm) on its surface], is involved in the pathogenesis of IgAN. METHODS: Cnm-positive S. mutans isolated from a patient with IgAN was intravenously administered to specific pathogen-free Sprague-Dawley rats to evaluate their kidney conditions. RESULTS: The urinary protein level of the S. mutans group reached a plateau at 30 days, with increased numbers of mesangial cells and an increased mesangial matrix. The numbers of rats with IgA-positive and/or C3-positive glomeruli were significantly greater in the S. mutans group than in the control group at 45 days (P < 0.05). Electron microscopy analyses revealed electron-dense depositions in the mesangial area among rats in the S. mutans group. There were significantly more CD68-positive cells (macrophages) in the glomeruli of the S. mutans group than in the glomeruli of the control group during the late phase (P < 0.05), similar to the findings in patients with IgAN. CONCLUSION: Our results suggested that intravenous administration of Cnm-positive S. mutans caused transient induction of IgAN-like lesions in rats.
Assuntos
Glomerulonefrite por IGA/microbiologia , Rim/microbiologia , Infecções Estreptocócicas/microbiologia , Streptococcus mutans/patogenicidade , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Complemento C3/metabolismo , Modelos Animais de Doenças , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/patologia , Humanos , Imunoglobulina A/metabolismo , Rim/imunologia , Rim/ultraestrutura , Macrófagos/imunologia , Macrófagos/microbiologia , Masculino , Ratos Sprague-Dawley , Infecções Estreptocócicas/complicações , Streptococcus mutans/isolamento & purificação , Fatores de TempoRESUMO
Streptococcus mutans is known to be a major causative agent of dental caries, and strains expressing the cell surface collagen-binding Cnm protein contribute to the development of several systemic diseases. A relationship between tonsillar immunity and glomerulonephritis has been recognized in IgA nephropathy (IgAN), and specific pathogens may have effects on tonsillar immunity (mucosal immunity). Here, we present findings showing a relationship between the presence of Cnm-positive S. mutans strains in the tonsils of IgAN patients and IgAN condition/pathogenesis. Analyses of tonsillar specimens obtained from patients with IgAN (n = 61) and chronic tonsillitis (controls; n = 40) showed that the Cnm protein-positive rate was significantly higher in IgAN patients. Among IgAN patients, the tonsillar Cnm-positive group (n = 15) had a significantly higher proportion of patients with high urinary protein (>1.5 g/gCr) and lower serum albumin level than the Cnm-negative group (n = 46). Additionally, Cnm protein and CD68, a common human macrophage marker, were shown to be merged in the tonsils of IgAN patients. These findings suggest that Cnm-positive S. mutans strains in the tonsils may be associated with severe IgAN.