RESUMO
Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis. Several observations suggest that gut microbiota could be implicated in IgAN pathophysiology. Aiming at exploring whether microbiota modulation is able to influence disease outcome, we performed fecal microbiota transplantation (FMT) from healthy controls (HC-sbjs), non-progressor (NP-pts) and progressor (P-pts) IgAN patients to antibiotic-treated humanized IgAN mice (α1KI-CD89Tg), by oral gavage. FMT was able to modulate renal phenotype and inflammation. On one hand, the microbiota from P-pts was able to induce an increase of serum BAFF and galactose deficient-IgA1 levels and a decrease of CD89 cell surface expression on blood CD11b+ cells which was associated with soluble CD89 and IgA1 mesangial deposits. On the other hand, the microbiota from HC-sbjs was able to induce a reduction of albuminuria immediately after gavage, an increased cell surface expression of CD89 on blood CD11b+ cells and a decreased expression of KC chemokine in kidney. Higher serum BAFF levels were found in mice subjected to FMT from IgAN patients. The main bacterial phyla composition and volatile organic compounds profile significantly differed in mouse gut microbiota. Microbiota modulation by FMT influences IgAN phenotype opening new avenues for therapeutic approaches in IgAN.
Assuntos
Bactérias/metabolismo , Transplante de Microbiota Fecal , Microbioma Gastrointestinal , Glomerulonefrite por IGA/terapia , Rim/microbiologia , Animais , Antígenos CD/genética , Antígenos CD/metabolismo , Fator Ativador de Células B/sangue , Estudos de Casos e Controles , Modelos Animais de Doenças , Disbiose , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/microbiologia , Humanos , Imunoglobulina A/genética , Imunoglobulina A/metabolismo , Rim/imunologia , Rim/metabolismo , Masculino , Camundongos Transgênicos , Fenótipo , Receptores Fc/genética , Receptores Fc/metabolismo , Compostos Orgânicos Voláteis/metabolismoRESUMO
BACKGROUND: The clinicopathological and prognostic features of IgA-dominant postinfectious glomerulonephritis and its difference from the primary IgA nephropathy remains to be investigated. METHODS: The clinical and pathological data of 6542 patients who underwent renal biopsy from 2009 to 2020 in our hospital were reviewed and 50 patients who met the selection criteria of IgA-dominant postinfectious glomerulonephritis were enrolled to conduct a retrospective and observational single-center study. The selection criteria were: meet the characteristics of IgA dominance or codominance in immunofluorescence, and conform to 3 of the following 5 criteria: 1.Clinical or laboratory evidence show that there is infection before or at the onset of glomerulonephritis; 2.The level of serum complement decreased; 3.Renal pathology is consistent with endocapillary proliferative glomerulonephritis; 4. Glomerular immunofluorescence staining showed complement C3 dominance or codominance; 5. Hump-like subepithelial immune complex deposition was observed under electron microscopy. According to age, sex, renal function (estimated glomerular filtration rate, eGFR) and follow-up time, the control group was constructed with 1:3 matched cases of primary IgA nephropathy. The clinicopathological and prognostic differences between the two groups were analyzed. RESULTS: The most common histological pattern of IgA-dominant postinfectious glomerulonephritis was acute endocapillary proliferative glomerulonephritis and exudative glomerulonephritis. Immunofluorescence showed mainly IgA deposition or IgA deposition only, mainly deposited in the mesangial area (deposition rate 100 %), with typical C3 high-intensity staining (intensity++~+++), mainly deposited in the mesangial area (deposition rate 92.0 %). The fluorescence intensity of kappa is usually not weaker than lambda. The probability of the appearance of typical hump-like electron deposition under electron microscopy is low. Compared to primary IgA nephropathy, patients with IgA-dominant postinfectious glomerulonephritis had higher proportion of crescents (p = 0. 005) and endocapillary hypercellularity (p < 0.001) in pathological manifestations. Using serum creatinine level doubled of the baseline or reached end-stage renal disease as the endpoint, the prognosis of IgA-dominant postinfectious glomerulonephritis patients was worse than that of primary IgA nephropathy patients (p = 0.013). CONCLUSIONS: The clinicopathological features of patients with IgA-dominant postinfectious glomerulonephritis was different from that of primary IgA nephropathy, and the prognosis was worse.
Assuntos
Glomerulonefrite por IGA/microbiologia , Glomerulonefrite por IGA/patologia , Infecções/complicações , Adulto , Idoso , Idoso de 80 Anos ou mais , Complexo Antígeno-Anticorpo , Complemento C3/análise , Creatinina/sangue , Feminino , Imunofluorescência , Seguimentos , Glomerulonefrite por IGA/imunologia , Humanos , Imunoglobulina A/análise , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
IgA nephropathy is one of the leading causes of chronic kidney disease in Japan. Since the origin and mechanisms by which IgA nephropathy develops currently remain unclear, a confirmed disease diagnosis is currently only possible by highly invasive renal biopsy. With the background of the salivary microbiome as a rich source of biomarkers for systemic diseases, we herein primarily aimed to investigate the salivary microbiome as a tool for the non-invasive diagnosis of IgA nephropathy. In a comparison of salivary microbiome profiles using 16S rRNA amplicon sequencing, significant differences were observed in microbial diversity and richness between IgA nephropathy patients and healthy controls. Furthermore, recent studies reported that patients with IgA nephropathy are more likely to develop inflammatory bowel diseases and that chronic inflammation of the tonsils triggered the recurrence of IgA nephropathy. Therefore, we compared the salivary microbiome of IgA nephropathy patients with chronic tonsillitis and ulcerative colitis patients. By combining the genera selected by the random forest algorithm, we were able to distinguish IgA nephropathy from healthy controls with an area under the curve (AUC) of 0.90, from the ulcerative colitis group with AUC of 0.88, and from the chronic tonsillitis group with AUC of 0.70. Additionally, the genus Neisseria was common among the selected genera that facilitated the separation of the IgA nephropathy group from healthy controls and the chronic tonsillitis group. The present results indicate the potential of the salivary microbiome as a biomarker for the non-invasive diagnosis of IgA nephropathy.
Assuntos
Bactérias/isolamento & purificação , Disbiose/microbiologia , Glomerulonefrite por IGA/microbiologia , Microbiota , Saliva/microbiologia , Adulto , Área Sob a Curva , Bactérias/classificação , Bactérias/genética , Estudos de Coortes , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
INTRODUCTION: The alteration of the gut microbiome in the gut-kidney axis has been associated with a pro-inflammatory state and chronic kidney disease (CKD). A small-scaled Italian study has shown an association between the gut microbiome and Immunoglobulin A Nephropathy (IgAN). However, there is no data on gut microbiota in IgAN in the Asian population. This study compares the gut microbial abundance and diversity between healthy volunteers and Malaysian IgAN cohort. METHODS: A comparative cross-sectional study was conducted involving biopsy-proven IgAN patients in clinical remission with matched controls in a Malaysian tertiary centre. Demographic data, routine blood and urine results were recorded. Stool samples were collected and their DNA was extracted by 16S rRNA gene sequencing to profile their gut microbiota. RESULTS: Thirty-six IgAN patients (13 male; 23 female) with the mean age of 45.5 ± 13.4 years and median estimated glomerular filtration rate (eGFR) of 79.0 (62.1-92.2) mls/min/1.73m2 with median remission of 7 years were analysed and compared with 12 healthy controls (4 male; 8 female) with the mean age of 46.5 ± 13.5 years and eGFR of 86.5 (74.2-93.7) mls/min/1.73m2. Other demographic and laboratory parameters such as gender, ethnicity, body mass index (BMI), haemoglobin, serum urea and serum albumin were comparable between the two groups. There were no significant differences seen in the Operational Taxonomic Unit (OTU) and alpha diversity (Shannon index) between IgAN and healthy controls. Alpha diversity increased with increasing CKD stage (p = 0.025). Firmicutes/Bacteroidetes (F/B) ratio was low in both IgAN and healthy cohort. Fusobacteria phylum was significantly increased (p = 0.005) whereas Euryarchaoeota phylum was reduced (p = 0.016) in the IgAN group as compared to the control cohort. CONCLUSION: Although we found no differences in OTU and alpha diversity between IgAN in remission and control cohort, there were some differences between the two groups at phylum level.
Assuntos
Povo Asiático , Microbioma Gastrointestinal , Glomerulonefrite por IGA/etnologia , Glomerulonefrite por IGA/microbiologia , Adulto , Povo Asiático/genética , Estudos Transversais , Feminino , Microbioma Gastrointestinal/genética , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S , Análise de Sequência de RNARESUMO
BACKGROUND: Immunoglobulin A nephropathy (IgAN) is the most common glomerulonephritis worldwide, characterized by mesangial polymeric IgA1 deposition. IgAN is believed to develop owing to aberrant mucosal immunoreaction against commensals in the tonsils. However, the exact interrelation between pathogenic IgA and mucosal microbiota in IgAN patients is unclear. METHODS: Biopsy-proven IgAN or recurrent tonsillitis (RT) patients who had undergone tonsillectomy were enrolled. We used 16S ribosomal RNA gene amplicon sequencing with a flow cytometry-based bacterial cell sorting technique) and immunoglobulin repertoire sequencing of the IgA heavy chain to characterize IgA-coated bacteria of the tonsillar microbiota (IgA-SEQ) and their corresponding IgA repertoire. Furthermore, we fractionated patient serum using gel-filtration chromatography and performed flow cytometry-based analysis of IgA binding to bacteria cultured from incised tonsils. RESULTS: Tonsillar proliferation-inducing ligand and B-cell activating factor levels were significantly higher in IgAN than in RT patients. IgA-SEQ for tonsillar microbiota revealed the preferential binding ability of IgA to Bacteroidetes in IgAN tonsils compared with those from RT patients. Expression of immunoglobulin heavy (IGH) constant alpha 1 with IGH variable 3-30 was significantly higher in IgAN than that in RT, and positively correlated with the IgA-coated enrichment score of Bacteroidetes. Serum polymeric IgA, comprising high levels of GdIgA1, exhibited considerable binding to Bacteroidetes strains cultured from the tonsils of IgAN patients. CONCLUSIONS: These findings provide evidence that aberrant mucosal immune responses to tonsillar anaerobic microbiota, primarily consisting of members of the phylum Bacteroidetes, are involved in IgAN pathophysiology.
Assuntos
Glomerulonefrite por IGA/complicações , Imunidade nas Mucosas/imunologia , Microbiota , Tonsila Palatina/microbiologia , Tonsilite/complicações , Adulto , Feminino , Citometria de Fluxo , Glomerulonefrite por IGA/microbiologia , Glomerulonefrite por IGA/patologia , Humanos , Masculino , Transdução de Sinais , Tonsilectomia , Tonsilite/imunologia , Tonsilite/microbiologiaRESUMO
Staphylococcus infection-associated glomerulonephritis (SAGN) and primary IgA nephropathy (IgAN) are separate disease entities requiring different treatment approaches. However, overlapping histologic features may cause a diagnostic dilemma. An exploratory proteomic study to identify potential distinguishing biomarkers was performed on formalin fixed paraffin embedded kidney biopsy tissue, using mass spectrometry (HPLC-MS/MS) (n = 27) and immunohistochemistry (IHC) (n = 64), on four main diagnostic groups-SAGN, primary IgAN, acute tubular necrosis (ATN) and normal kidney (baseline transplant biopsies). Spectral counts modeled as a negative binomial distribution were used for statistical comparisons and in silico pathway analysis. Analysis of variance techniques were used to compare groups and the ROC curve to evaluate classification algorithms. The glomerular proteomes of SAGN and IgAN showed remarkable similarities, except for significantly higher levels of monocyte/macrophage proteins in SAGN-mainly lysozyme and S100A9. This finding was confirmed by IHC. In contrast, the tubulointerstitial proteomes were markedly different in IgAN and SAGN, with a lower abundance of metabolic pathway proteins and a higher abundance of extracellular matrix proteins in SAGN. The stress protein transglutaminase-2 (TGM2) was also significantly higher in SAGN. IHC of differentially-expressed glomerular and tubulointerstitial proteins can be used to help discriminate between SAGN and IgAN in ambiguous cases.
Assuntos
Glomerulonefrite por IGA/metabolismo , Glomerulonefrite por IGA/microbiologia , Imunoglobulina A/metabolismo , Infecções Estafilocócicas/metabolismo , Infecções Estafilocócicas/microbiologia , Adulto , Idoso , Biomarcadores/metabolismo , Biópsia/métodos , Estudos de Casos e Controles , Feminino , Proteínas de Ligação ao GTP/metabolismo , Taxa de Filtração Glomerular/fisiologia , Glomerulonefrite por IGA/patologia , Humanos , Glomérulos Renais/metabolismo , Glomérulos Renais/microbiologia , Glomérulos Renais/patologia , Masculino , Pessoa de Meia-Idade , Proteína 2 Glutamina gama-Glutamiltransferase , Curva ROC , Infecções Estafilocócicas/patologia , Staphylococcus/patogenicidade , Espectrometria de Massas em Tandem/métodos , Transglutaminases/metabolismoRESUMO
Immunoglobulin A nephropathy (IgAN) is a common glomerular disease. The pathogenesis of IgAN is associated with dysregulated intestinal mucosal immunity. However, whether gut microbial modifications play a role in IgAN remains unclear. Blood and faecal samples were collected from 52 patients with IgAN and 25 healthy controls (HCs). The gut microbiome was analysed using the 16S ribosomal RNA gene. The levels of galactose-deficient IgA1 (Gd-IgA1), soluble cluster of differentiation 14 (sCD14), lipopolysaccharide binding protein (LBP), intercellular adhesion molecule-1 (ICAM-1), tumour necrosis factor α (TNF-α), interleukin-1, and C-reactive protein were quantified. Substantial differences in the gut microbiota were identified between patients with IgAN and HCs (P < 0.05). Bacteroides and Escherichia-Shigella levels were significantly higher in patients with IgAN than in HCs, while Bifidobacterium and Blautia spp. Levels were lower. Higher proportions of Escherichia-Shigella and lower proportions of Bifidobacterium spp. were observed in patients with IgAN with high urine RBC count (≥10/HP) and proteinuria (≥1 g/24 h) levels. Correlation analysis was used to assess the association between gut microbiota and biomarkers in patients with IgAN. The results showed that Prevotella 7 levels were negatively correlated with Gd-IgA1, LBP, sCD14, ICAM-1, and TNF-α levels, while Bifidobacterium spp. Levels presented a significant inverse relationship with LBP and Gd-IgA1. Additionally, Escherichia-Shigella levels were negatively correlated with Prevotella 7. In patients with IgAN, gut modifications were characterised by an increase in the number of pathogenic bacteria and a reduction in the levels of beneficial bacteria, suggesting that the disturbance of intestinal microflora might be important in the severity of IgAN.
Assuntos
Microbioma Gastrointestinal/genética , Microbioma Gastrointestinal/imunologia , Glomerulonefrite por IGA/microbiologia , Proteínas de Fase Aguda , Adulto , Povo Asiático , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Biomarcadores/sangue , Biomarcadores/urina , Proteína C-Reativa/metabolismo , Proteínas de Transporte/sangue , Análise Discriminante , Fezes/microbiologia , Feminino , Glomerulonefrite por IGA/sangue , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/urina , Hematúria/microbiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Humanos , Imunoglobulina A/sangue , Molécula 1 de Adesão Intercelular/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Glicoproteínas de Membrana/sangue , Proteinúria/microbiologia , RNA Ribossômico 16S , Índice de Gravidade de DoençaRESUMO
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
BACKGROUND: Infection-related glomerulonephritis with IgA deposits (IRGN-IgA) is a rare disease but it is increasingly reported in the literature. Data regarding epidemiology and outcome are lacking, especially in Europe. We aimed to assess the clinical, pathologic and outcome data of IRGN-IgA. METHODS: Clinical and outcome data from patients from 11 French centers over the 2007-2017 period were collected retrospectively. We reviewed pathologic patterns and immunofluorescence of renal biopsies and evaluated C4d expression in IRGN-IgA. We analyzed the correlation between histological presentation and outcome. RESULTS: Twenty-seven patients (23 men, mean age: 62 ± 15 years) were included. Twenty-one (78%) had Staphylococcus aureus infection and twelve (44%) were diabetic. At the time of biopsy, 95.2% had haematuria, 48.1% had a serum creatinine level of > 4 mg/dL, and 16% had hypocomplementemia. The most common pathologic presentation included mesangial (88.9%) and endocapillary proliferative glomerulonephritis (88.9%) with interstitial fibrosis and tubular atrophy (IF/TA) (85.1%). Diffuse and global glomerular C4d expression was found in 17.8%, mostly in biopsies with acute or subacute patterns, and was associated with a short delay between infection and renal biopsy compared to segmental and focal staining. After median follow-up of 13.2 months, 23.1% died, 46.2% had persistent renal dysfunction and 15.4% reached end-stage renal disease. Renal outcome was correlated to IF/TA severity. CONCLUSIONS: Infection-related glomerulonephritis with IgA deposits is usually associated with Staphylococcus infections and mainly affects adult men. This entity has a poor prognosis which is correlated to interstitial fibrosis and tubular atrophy severity.
Assuntos
Glomerulonefrite por IGA/microbiologia , Glomerulonefrite por IGA/patologia , Infecções Estafilocócicas/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/complicações , Criança , Pré-Escolar , Feminino , França , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto JovemRESUMO
Association between pulmonary disease and IgA nephropathy (IgAN) has been previously reported. However, no association has been reported between hypersensitivity pneumonitis (HP) and IgAN. Here, we report about a patient with no particular medical history, who experienced worsening dyspnoea in the course of 1 month, with ground-glass opacity on chest CT and no improvement after antibiotic therapy. The patient was diagnosed as having HP based on the history of antigen exposure, detection of Trichosporon asahii-specific antibodies and bronchoscopy findings. Concomitantly, findings of renal biopsy revealed the IgAN diagnosis. The patient underwent corticosteroid therapy, with good outcomes for both HP and IgAN. This is the first report in the literature to describe summer-type HP complicated with IgAN.
Assuntos
Corticosteroides/uso terapêutico , Ar Condicionado/efeitos adversos , Alveolite Alérgica Extrínseca/microbiologia , Dispneia/microbiologia , Glomerulonefrite por IGA/microbiologia , Tricosporonose/diagnóstico , Alveolite Alérgica Extrínseca/tratamento farmacológico , Alveolite Alérgica Extrínseca/imunologia , Anticorpos Antifúngicos , Broncoscopia , Tosse , Dispneia/etiologia , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/imunologia , Habitação , Humanos , Imunoglobulina A/imunologia , Masculino , Pessoa de Meia-Idade , Radiografia Torácica , Estações do Ano , Resultado do Tratamento , Tricosporonose/tratamento farmacológico , Tricosporonose/imunologia , Tricosporonose/fisiopatologiaRESUMO
Mycobacterium tuberculosis(MTB)-related secondary immunoglobulin A (IgA) nephropathy is reported in a 72-year-old male patient. The patient was diagnosed to have MTB infection of the kidney and genitourinary tract which was diagnosed by the demonstration of the organism by GeneXpert Ultra and culture. Concurrent kidney biopsy showed IgA nephropathy. The patient responded to urethral double-J stenting and four-drug antituberculous therapy with improvement of kidney function and resolution of MTB. IgA nephropathy can present as primary glomerulonephritis or secondary to MTB infection.
Assuntos
Glomerulonefrite por IGA/microbiologia , Imunoglobulina A/imunologia , Rim/microbiologia , Mycobacterium tuberculosis/imunologia , Tuberculose/imunologia , Infecções Urinárias/microbiologia , Sistema Urinário/microbiologia , Idoso , Antituberculosos/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Humanos , Masculino , Mycobacterium tuberculosis/efeitos dos fármacos , Tuberculose/tratamento farmacológico , Sistema Urinário/imunologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/imunologiaRESUMO
Immunoglobulin A nephropathy (IgAN) is the most frequent pathological diagnosis of tuberculosis (TB)-associated glomerulonephritis. Diagnosing TB-associated IgAN (TB-IgAN) is difficult because of its non-specific and insidious symptoms. An inaccurate diagnosis of TB-IgAN could result in the spread of TB and reduced renal function. Haematuria and proteinuria in conjunction with TB should be assessed because of the potential for diagnosis of IgAN. Renal biopsy is important in securing an accurate diagnosis prior to initiating treatment. Detection of Mycobacterium tuberculosis DNA and assessment of early secreted antigenic target of 6 kDa in renal biopsy tissues may have great potential diagnostic value in patients with TB-IgAN. Anti-TB therapy can effectively alleviate TB and TB-IgAN.
Assuntos
Glomerulonefrite por IGA/microbiologia , Subpopulações de Linfócitos T/imunologia , Tuberculose/imunologia , Antituberculosos/uso terapêutico , Diagnóstico Diferencial , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/imunologia , Glucocorticoides/uso terapêutico , Humanos , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/microbiologiaRESUMO
Postinfectious glomerulonephritis (PIGN) generally occurs in association with staphylococcal infection. We present the first reported case of IgA-dominant PIGN after Escherichia coli infection in a renal-transplant recipient. A 65-year-old patient with stable allograft function and E. coli urosepsis was treated with ciprofloxacin for 2 weeks with excellent response. One week later he developed proteinuria 16 g/day. Renal biopsy finding revealed IgA-dominant PIGN. He received steroid pulses and intravenous imunoglobulins without effect and had started with hemodialysis.
Assuntos
Infecções por Escherichia coli/imunologia , Escherichia coli/patogenicidade , Glomerulonefrite por IGA/microbiologia , Imunoglobulina A/imunologia , Transplante de Rim/efeitos adversos , Sepse/microbiologia , Idoso , Aloenxertos/imunologia , Aloenxertos/microbiologia , Biópsia , Ciprofloxacina/uso terapêutico , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/microbiologia , Glomerulonefrite por IGA/imunologia , Glomerulonefrite por IGA/terapia , Glucocorticoides/uso terapêutico , Humanos , Rim/imunologia , Rim/microbiologia , Falência Renal Crônica/cirurgia , Masculino , Diálise Renal , Sepse/tratamento farmacológico , Sepse/imunologiaRESUMO
Increasing evidences have shown that Helicobacter pylori (Hp) is a pathogen closely related to extra-gastric disorders. Our previous in vitro studies had demonstrated that Hp infection, at least via cytotoxin-associated gene A protein (CagA), might play an important role in the pathogenesis of IgA nephropathy (IgAN) by stimulating proliferation and ectopic synthesis of aberrantly glycosylated IgA1 of B cells. However, the relevant clinical evidence of IgAN resulted from Hp infection remain to be elucidated. This study aimed to investigate the risk incidence of IgAN caused by Hp infection. 22 primary IgAN, 20 non-IgA nephropathy (n-IgAN), and 30 healthy controls were included in this study. We found that the rate of IgG anti-Hp seropositivity was significantly improved in IgAN, but the current Hp infection was similar in all groups. The production and underglycosylation of IgA1 tended to increase in IgAN patients with IgG anti-Hp seropositivity. A tendency toward increased the risk of clinical prognosis was seen in IgAN with Hp infection. Hp antigen and CagA were only deposited in renal tubules, and enhanced antigen deposition in response to Hp was observed in IgAN. Our study suggested that Hp infection might have a pathogenic role in IgAN through giving rise to strongly mucosal immune response, and based on damage of renal tubular.
Assuntos
Glomerulonefrite por IGA/etiologia , Infecções por Helicobacter/complicações , Helicobacter pylori/isolamento & purificação , Túbulos Renais/patologia , Adulto , Anticorpos Antibacterianos/análise , Antígenos de Bactérias/análise , Biópsia , Ensaio de Imunoadsorção Enzimática , Feminino , Glomerulonefrite por IGA/diagnóstico , Glomerulonefrite por IGA/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/imunologia , Humanos , Imunoglobulina A/imunologia , Imunoglobulina A/metabolismo , Imuno-Histoquímica , Túbulos Renais/metabolismo , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: In children and adults, Henoch-Schönlein purpura (HSP) has a characteristic clinical presentation that includes a purpuric lower extremity skin rash, IgA-dominant glomerulonephritis, and abdominal and joint pain. A similar clinical presentation can be seen in adults who have a systemic infection with methicillin-resistant Staphylococcus aureus. It is critically important to distinguish the IgAdominant glomerulonephritis of HSP from the IgA-dominant glomerulonephritis of staphylococcal infection, because HSP may need to be treated with corticosteroids and immunosuppressives, while Staphylococcus infection-associated glomerulonephritis requires antibiotics. DESIGN: We searched our renal biopsy database for cases of Staphylococcus infection-associated IgA-dominant glomerulonephritis, to identify those with an HSP-like presentation. Their clinical, laboratory, and biopsy findings are reviewed. RESULTS: Between 2004 and 2011, we identified 37 patients with culture-proven Staphylococcus infection-associated glomerulonephritis. Of these, 8 (22%) had an HSP-like presentation manifested by lower extremity purpuric skin rash. Mesangial IgA and C3 deposits were consistent findings on kidney biopsy. Crescents were uncommon. Four of the 8 patients received glucocorticoid (steroid) therapy for a presumed diagnosis of HSP. Renal function worsened in 3 patients, and 1 patient ultimately improved but developed sepsis during the course. Overall, renal outcome was poor in 71% of the cases despite mild chronic renal injury in the biopsy. CONCLUSION: In adult patients with an HSPlike presentation, a high index of suspicion for underlying Staphylococcal infection is warranted. Blood cultures are frequently negative. Cultures from the site of infection should be performed. Steroid treatment did not improve outcomes. Renal outcomes were frequently poor.
Assuntos
Erros de Diagnóstico , Glomerulonefrite por IGA/diagnóstico , Vasculite por IgA/diagnóstico , Glomérulos Renais/patologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Feminino , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulonefrite por IGA/microbiologia , Glomerulonefrite por IGA/patologia , Humanos , Vasculite por IgA/tratamento farmacológico , Vasculite por IgA/patologia , Imunossupressores/uso terapêutico , Glomérulos Renais/imunologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Pele/patologia , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Procedimentos DesnecessáriosRESUMO
AIM: A new animal model of immunoglobulin A nephropathy (IgAN) was made by infecting mice with Mycoplasma penetrans (Mpe). To examine the pathogenesis of IgAN induced by Mpe infection, tumour necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and nuclear factor-kB (NF-kB) protein levels were compared among study groups. METHODS: To make an experimental IgAN animal model, mice were infected with Mpe, SP-4 medium or phosphate-buffered saline (PBS) via the urinary tract. To compare changes in the classical IgAN model, TNF-alpha and IL-6 RNA expression levels were measured using RT-PCR, and NF-kB protein was measured using EMSA. RESULTS: By producing a urinary tract infection with Mpe, we developed a new animal model of IgAN with a 100% success rate. There was no difference with the classical animal model. We also observed IgG deposition in 66.67% of the Mpe-infection group. Glomerular cell and mesangial matrix proliferation was greater in the Mpe-infection group than in the control groups (p<0.05). In the Mpe-infection and classical groups, TNF-alpha and IL-6 expression levels were much higher than in the control groups (p<0.01). NF-kB expression was much higher in the Mpe-infection group (p<0.05). CONCLUSIONS: We made a new IgAN animal model that will offer a new direction for IgAN research. The activation of inflammation factors was associated with the Mpe induction of IgAN.
Assuntos
Modelos Animais de Doenças , Glomerulonefrite por IGA/microbiologia , Infecções por Mycoplasma/complicações , Mycoplasma penetrans , Animais , Feminino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
BACKGROUND: IgA-dominant postinfectious glomerulonephritis (PIGN) is a unique form of PIGN. It has been linked to staphylococcal infection and underlying diabetic glomerulosclerosis. However, the significance of glomerular IgA-dominant deposition in PIGN remains unclear. METHODS: We reported 10 patients with IgA-dominant PIGN encountered at a single center, each characterized by subepithelial humps. Their demographic, clinical, and renal biopsy findings were summarized and compared with the data of 32 patients with non-IgA-dominant PIGN. RESULTS: The mean age was 57 years. An immunocompromised background was present in 70% of patients; only one patient had diabetes mellitus. The causative infectious agents included Staphylococcus (30%), Streptococcus (20%), and gram-negative organisms (50%). Decreased serum complement was present in 60%. Increased serum IgA was noted in 75%. The mean peak serum creatinine was 5.1 mg/dL, and 20% required acute dialysis. Diffuse endocapillary-proliferative glomerulonephritis was found in all cases, and three patients also had crescentic glomerulonephritis. Electron microscopy revealed large subepithelial hump-shaped deposits in all cases. At the last follow-up, one patient had died, five had achieved complete recovery, three had persistent renal insufficiency, and one was on chronic dialysis. Compared to patients with non-IgA-dominant PIGN, increased serum IgA was more commonly present in IgA-dominant group (p = 0.007). There were no significant differences in other clinical parameters and outcome between the two groups. CONCLUSIONS: IgA-dominant PIGN resembles poststreptococcal glomerulonephritis in its histological spectrum and ultrastructural appearance. Increasing serum IgA may be involved in the pathogenesis of this form of PIGN. Our data suggested that IgA-dominant PIGN was not peculiar to staphylococcal infection and diabetic patients.
Assuntos
Glomerulonefrite por IGA/epidemiologia , Adulto , Idoso , Biópsia , Feminino , Glomerulonefrite por IGA/microbiologia , Glomerulonefrite por IGA/patologia , Humanos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Infecções Estafilocócicas/complicações , Taiwan/epidemiologia , Adulto JovemRESUMO
Immunoglobin A-dominant postinfectious glomerulonephritis is a distinct clinicopathologic entity that has been linked to staphylococcal infection, including methicillin-resistant Staphylococcus aureus. An association with diabetic nephropathy has been suggested. Although the morphologic features resemble other forms of postinfectious glomerulonephritis, immunofluorescence shows dominant or codominant immunoglobulin A immune-complex deposits. We encountered 7 patients with immunoglobulin A-dominant postinfectious glomerulonephritis over 2½ years at a single center. All patients presented with renal failure and with varying degrees of hematuria, proteinuria, and hypertension. All patients had clinical infections at the time of presentation. Four patients had documented S aureus infections. Three patients had methicillin-resistant S aureus infection within 2 weeks before the renal biopsy; 2 of these had an infection with a community-associated methicillin-resistant S aureus-10 clone, equivalent to USA300. One patient had methicillin-sensitive S aureus infection. Diffuse proliferative endocapillary glomerulonephritis was found in all cases; 1 had a membranoproliferative glomerulonephritic pattern, and 1 patient had a crescentic glomerulonephritis. Immunofluorescence microscopy showed dominant immunoglobulin A subepithelial and mesangial immune complexes in 5 patients and codominant immunoglobulin A with immunoglobulin G in 2 patients. Electron microscopy revealed large subepithelial deposits ("humps") in all cases. Only 1 patient had clinical diabetes mellitus but without biopsy-proven diabetic nephropathy. Two patients died, including the patient with diabetes mellitus. Renal function improved after therapy in 5 nondiabetic patients, but full recovery was not seen during the follow-up. We confirm that immunoglobulin A-dominant postinfectious glomerulonephritis is often associated with S aureus and methicillin-resistant S aureus infections, and, for the first time, we document an association with community-associated methicillin-resistant S aureus.
Assuntos
Infecções Comunitárias Adquiridas/patologia , Nefropatias Diabéticas/patologia , Glomerulonefrite por IGA/patologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/patologia , Idoso , Idoso de 80 Anos ou mais , Infecções Comunitárias Adquiridas/microbiologia , Nefropatias Diabéticas/complicações , Feminino , Imunofluorescência , Glomerulonefrite por IGA/microbiologia , Humanos , Glomérulos Renais/imunologia , Glomérulos Renais/patologia , Masculino , Resistência a Meticilina , Pessoa de Meia-Idade , Insuficiência Renal/etiologia , Insuficiência Renal/patologia , Infecções Estafilocócicas/complicaçõesRESUMO
A 66-year-old man with a two-year history of hepatitis C viral liver cirrhosis, was diagnosed as having ascending colon cancer. Right hemicolectomy was performed, and a drain was fed down to the anastomosis. On post-operative day (POD) 9, and methicillin-sensitive Staphylococcus aureus (MSSA) was isolated from both drains. After POD 12, relapsing persistent diarrhea with some blood occurred. On POD 20, the temperature increased to 39 degrees C, with symmetrical purpura and swelling in the femurs, and knee arthralgia developed. HSP was suspected. Clinical follow-up showed slight spontaneous reduction of diarrhea and purpura on POD 26. However, despite the negative drain culture, the high fever was maintained on POD 27. Therefore, intravenous steroid pulse therapy was performed. The purpura subsequently disappeared, except for a slight pigmentation and the temperature returned to normal. A renal biopsy was performed 26 days after the appearance of purpura. Pathological views demonstrated acute focal segmental glomerulonephritis-like nephropathy in addition to cirrhotic nephropathy with a membranoproliferative glomerulonephritis (MPGN)-like pattern and the mesangial proliferative glomerulonephritis type. We describe a case of Henoch-Schönlein purpura (HSP) after postoperative Staphylococcus aureus infection of the intra-abdominal drain with IgA nephropathy associated with hepatitis C virus liver cirrhosis.