RESUMO
BACKGROUND: Podocytes, as intrinsic renal cells, can also express MHC-II and costimulatory molecules under inflammatory conditions, suggesting that they may act as antigen-presenting cells (APCs) to activate immune cell responses and then lead to immune-mediated renal injury. They are already recognized as main targets in the pathogenic mechanism of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN). Previous studies also have indicated that inflammatory cells infiltration and immune-mediated tissue injury are evident in the kidney samples of patients with HBV-GN. However, the role of podocytes immune disorder in the pathogenic mechanism of HBV-GN remains unclear. METHODS: Renal function and inflammatory cells infiltration were measured in HBV transgenic (HBV-Tg) mice. In vitro, podocytes/CD4+ T cells or macrophages co-culture system was established. Then, the expression of HBx, CD4, and CD68 was determined by immunohistochemistry, while the expression of MHC-II, CD40, and CD40L was determined by immunofluorescence. Co-stimulatory molecules expression was examined by flow cytometry. The levels of inflammatory factors were detected by ELISA. RESULTS: In vivo, renal function was obviously impaired in HBV-Tg mice. HBx was significantly upregulated and immune cells infiltrated in the glomerulus of HBV-Tg mice. Expression of MHC-II and costimulatory molecule CD40 increased in the podocytes of HBV-Tg mice; CD4+ T cells exhibited increased CD40L expression in glomerulus. In vitro, CD40 expression was markedly elevated in HBx-podocytes. In co-culture systems, HBx-podocytes stimulated CD4+ T cells activation and caused the imbalance between IFN-γ and IL-4. HBx-podocytes also enhanced the adhesion ability of macrophages and induced the release of proinflammatory mediators. CONCLUSION: Taken together, these podocyte-related immune disorder may be involved in the pathogenic mechanism of HBV-GN.
Assuntos
Glomerulonefrite , Vírus da Hepatite B , Camundongos Transgênicos , Podócitos , Transativadores , Proteínas Virais Reguladoras e Acessórias , Animais , Podócitos/imunologia , Podócitos/patologia , Podócitos/metabolismo , Camundongos , Transativadores/metabolismo , Transativadores/genética , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Glomerulonefrite/virologia , Vírus da Hepatite B/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Hepatite B/imunologia , Hepatite B/complicações , Humanos , Técnicas de Cocultura , Masculino , Modelos Animais de Doenças , Camundongos Endogâmicos C57BLRESUMO
Since March 2020, the outbreak of Sars-CoV-2 pandemic has changed medical practice and daily routine around the world. Huge efforts from pharmacological industries have led to the development of COVID-19 vaccines. In particular two mRNA vaccines, namely the BNT162b2 (Pfizer-BioNTech) and the mRNA-1273 (Moderna), and a viral-vectored vaccine, i.e. ChAdOx1 nCoV-19 (AstraZeneca), have recently been approved in Europe. Clinical trials on these vaccines have been published on the general population showing a high efficacy with minor adverse events. However, specific data about the efficacy and safety of these vaccines in patients with immune-mediated inflammatory diseases (IMIDs) are still lacking. Moreover, the limited availability of these vaccines requires prioritizing some vulnerable categories of patients compared to others. In this position paper, we propose the point of view about the management of COVID-19 vaccination from Italian experts on IMIDs and the identification of high-risk groups according to the different diseases and their chronic therapy.
Assuntos
Vacinas contra COVID-19/imunologia , COVID-19/complicações , COVID-19/prevenção & controle , Doenças do Sistema Imunitário/virologia , Vacinação/métodos , Diabetes Mellitus/imunologia , Diabetes Mellitus/virologia , Europa (Continente) , Prova Pericial , Glomerulonefrite/complicações , Glomerulonefrite/imunologia , Glomerulonefrite/virologia , Humanos , Inflamação/imunologia , Inflamação/virologia , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/virologia , Pneumopatias/complicações , Pneumopatias/imunologia , Pneumopatias/virologia , Pandemias/prevenção & controle , Doenças Reumáticas/complicações , Doenças Reumáticas/imunologia , Doenças Reumáticas/virologia , Dermatopatias/complicações , Dermatopatias/imunologia , Dermatopatias/virologia , Uveíte/complicações , Uveíte/imunologia , Uveíte/virologiaRESUMO
Pathogens such as the Epstein Barr virus (EBV) have long been implicated in the etiology of systemic lupus erythematosus (SLE). The Epstein Barr virus nuclear antigen I (EBNA-1) has been shown to play a role in the development of anti-nuclear antibodies characteristic of SLE. One mechanism by which EBV may play a role in SLE is molecular mimicry. We previously generated two monoclonal antibodies (mAbs) to EBNA-1 and demonstrated that they cross-react with double-stranded DNA (dsDNA). In the present study, we demonstrate that these mAbs have pathogenic potential. We show that they can bind to isolated rat glomeruli and that binding can be greatly diminished by pretreatment of glomeruli with DNase I, suggesting that these mAbs bind dsDNA in the kidney. We also demonstrate that these antibodies can deposit in the kidney when injected into mice and can induce proteinuria and elicit histopathological alterations consistent with glomerulonephritis. Finally, we show that these antibodies can cross-react with laminin and collagen IV in the extracellular matrix suggesting that direct binding to the glomerular basement membrane or mesangial matrix may also contribute to the antibody deposition in the kidney. In summary, our results indicate that EBNA-1 can elicit antibodies that cross-react with dsDNA, that can deposit in the kidney, and induce kidney damage. These results are significant because they support the role of a viral protein in SLE and lupus nephritis.
Assuntos
Anticorpos Antinucleares/toxicidade , Anticorpos Monoclonais/toxicidade , Anticorpos Antivirais/imunologia , DNA/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Antígenos Nucleares do Vírus Epstein-Barr/imunologia , Glomérulos Renais/imunologia , Animais , Anticorpos Antinucleares/imunologia , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/isolamento & purificação , Colágeno/imunologia , Reações Cruzadas/imunologia , Desoxirribonuclease I , Infecções por Vírus Epstein-Barr/metabolismo , Matriz Extracelular/genética , Matriz Extracelular/imunologia , Feminino , Membrana Basal Glomerular/imunologia , Membrana Basal Glomerular/metabolismo , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Glomerulonefrite/virologia , Células HEK293 , Humanos , Imunoglobulina G/imunologia , Glomérulos Renais/patologia , Laminina/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Mimetismo Molecular , Proteinúria/imunologia , Ratos , Ratos Sprague-DawleyRESUMO
INTRODUCTION: Occult hepatitis B virus (HBV) infection, defined as negative hepatitis B surface antigen (HBsAg) but detectable HBV DNA in serum and liver tissue, has very rarely been described in cryoglobulinemia (CG) patients. This case report sheds light on the possible link between occult HBV infection and CG. PATIENT CONCERNS: A 76-year-old man presented with rapidly deteriorating renal function within 1 year. DIAGNOSIS: Cryoglobulinemic glomerulonephritis was diagnosed through renal biopsy. Initially, the patient tested negative for HBsAg, but a low HBV viral load was later discovered, indicating an occult HBV infection. Further studies also revealed Waldenström macroglobulinemia (WM). INTERVENTIONS: We treated the patient as WM using plasma exchange and rituximab-based immunosuppressive therapy. OUTCOMES: After 1 cycle of immunosuppressive treatment, there was no improvement of renal function. Shortly after, treatment was discontinued due to an episode of life-threatening pneumonia. Hemodialysis was ultimately required. CONCLUSION: Future studies are needed to explore the link between occult HBV infection and CG, to investigate the mediating role of lymphomagenesis, and to examine the effectiveness of anti-HBV drugs in treating the group of CG patients with occult HBV infection. We encourage clinicians to incorporate HBV viral load testing into the evaluation panel for CG patients especially in HBV-endemic areas, and to test HBV viral load for essential CG patients in whom CG cannot be attributed to any primary disease.
Assuntos
Crioglobulinemia/complicações , Glomerulonefrite/complicações , Hepatite B/complicações , Macroglobulinemia de Waldenstrom/etiologia , Idoso , Crioglobulinemia/virologia , Glomerulonefrite/virologia , Antígenos de Superfície da Hepatite B/sangue , Humanos , Masculino , Macroglobulinemia de Waldenstrom/diagnóstico , Macroglobulinemia de Waldenstrom/virologiaRESUMO
OBJECTIVES: To study the pathologic spectrum of kidney diseases in patients with hepatitis C virus infection (HCV+). METHODS: Native kidney biopsy specimens in HCV+ patients were reviewed. RESULTS: A total of 9,836 native kidney biopsy specimens were evaluated from January 2007 to December 2016, of which 273 (2.8%) were from HCV+ patients, and of these, 115 (42.1%) had diagnoses consistent with HCV-associated glomerulonephritis (GN). Non-HCV-associated kidney diseases comprised most diagnoses (158 cases, 57.9%) including non-immune complex-mediated kidney diseases (127 cases, 46.5%) and other immune complex-mediated glomerular diseases (31 cases, 11.4%). Forty-one (40.6%) patients had HCV-associated GN among 101 HCV+ patients from 2007 to 2011 vs 74 (43.0%) patients with HCV-associated GN among 172 HCV+ patients from 2012 to 2016. HCV-associated GN showed five morphologic patterns: focal proliferative (5.2%), diffuse mesangial proliferative (50.4%), diffuse membranoproliferative (28.7%), proliferative GN with crescentic lesions (7.8%), and membranous patterns (7.8%). CONCLUSIONS: We found a spectrum of pathologic changes in renal biopsy specimens of HCV+ patients, with most having diseases unrelated to HCV infection, HCV-associated GN showing five morphologic patterns, and availability of effective HCV antiviral therapy not yet resulting in major changes in the spectrum of kidney diseases in these patients.
Assuntos
Glomerulonefrite/patologia , Hepatite C/patologia , Nefropatias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Glomerulonefrite/complicações , Glomerulonefrite/virologia , Hepatite C/complicações , Humanos , Rim/patologia , Nefropatias/complicações , Nefropatias/virologia , Masculino , Pessoa de Meia-Idade , Adulto JovemAssuntos
Glomerulonefrite/tratamento farmacológico , Glucocorticoides/administração & dosagem , Hepatite B/tratamento farmacológico , Metilprednisolona/administração & dosagem , Adulto , Feminino , Seguimentos , Glomerulonefrite/sangue , Glomerulonefrite/virologia , Hepatite B/sangue , Antígenos da Hepatite B/sangue , Humanos , Indução de Remissão , Fatores de Tempo , Resultado do TratamentoRESUMO
Alterations to the programmed cell death protein-1 (PD-1) pathway were previously shown to be involved in a poorer prognosis for patients with proliferative glomerulonephritis (PGN). Here, we investigated the association between several infectious agents and the expression of PD-1 and its ligand (PD-L1) on T and B lymphocytes in patients with PGN and nonproliferative glomerulonephritis (NPGN). A cohort of 45 newly-diagnosed patients (23 with PGN and 22 with NPGN) and 20 healthy volunteers was enrolled. The percentage of peripheral blood mononuclear cells expressing PD-1 and PD-L1 antigens was determined by flow cytometry. We found PD-1 and PD-L1 expression on T and B lymphocytes was higher in PGN patients than in NPGN patients and controls. We also found that reactivation of the Epstein-Barr virus (EBV) correlated with the expression of PD-1/PD-L1 antigens in patients with PGN. Further receiver operating characteristic analysis indicated that PD-1 expression could distinguish EBV-positive PGN patients from those with NPGN or healthy controls. The use of PD-1 expression as a non-invasive marker of PGN should be further investigated.
Assuntos
Linfócitos B/metabolismo , Antígeno B7-H1/metabolismo , Infecções por Vírus Epstein-Barr/complicações , Glomerulonefrite/virologia , Receptor de Morte Celular Programada 1/metabolismo , Linfócitos T/metabolismo , Adulto , Idoso , Estudos de Casos e Controles , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Glomerulonefrite/imunologia , Humanos , Leucócitos Mononucleares/metabolismo , Masculino , Pessoa de Meia-Idade , Curva ROC , Regulação para Cima , Adulto JovemRESUMO
BACKGROUND: The seroprevalence of human Parvovirus B19 (PVB19) is 70-85% in adults worldwide. PVB19 is the etiologic agent of the fifth disease, is a cause of aplastic anemia, and can be associated with kidney injury. We aimed to describe the cases of 4 patients with kidney injury related to PVB19 primary infection, and to evaluate the seroprevalence of PVB19 and the incidence of PVB19 primary infection in patients undergoing a native kidney biopsy. METHODS: Cases of PVB19 infection with kidney injury were reviewed from the archives of the department of Nephrology. A systematic screening of anti-PVB19 IgG and IgM antibodies and viral DNA was performed in sera from 100 consecutive patients with a kidney biopsy in 2017-2018. RESULTS: The 4 patients with PVB19 infection-associated kidney disease displayed: one lupus-like glomerulonephritis (GN) without lupus auto-antibodies, one minimal change disease with tubular necrosis, one secondary hemolytic and uremic syndrome and one membrano-proliferative GN. In the 100 patients biopsied, 67 had elevated anti-PVB19 IgG, among whom 8 had elevated IgM, without circulating viral DNA, without any particular renal pathological pattern. One additional patient showed a seroconversion at the time of kidney biopsy, which revealed a class V lupus nephritis. CONCLUSION: PVB19 primary infection can be associated with different kidney diseases. The seroprevalence of PVB19 among patients with a kidney biopsy is similar to the overall population, and primary infection is rarely documented (1%) after systematic screening. Whether PV19 is nephrotoxic, or triggers renal endothelial injury and immune activation, remains to be elucidated.
Assuntos
Injúria Renal Aguda/virologia , Anticorpos Antivirais/imunologia , DNA Viral/sangue , Eritema Infeccioso/imunologia , Parvovirus B19 Humano/imunologia , Injúria Renal Aguda/sangue , Injúria Renal Aguda/imunologia , Injúria Renal Aguda/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Eritema Infeccioso/sangue , Eritema Infeccioso/complicações , Feminino , Glomerulonefrite/sangue , Glomerulonefrite/imunologia , Glomerulonefrite/patologia , Glomerulonefrite/virologia , Glomerulonefrite Membranoproliferativa/sangue , Glomerulonefrite Membranoproliferativa/imunologia , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranoproliferativa/virologia , Síndrome Hemolítico-Urêmica/sangue , Síndrome Hemolítico-Urêmica/imunologia , Síndrome Hemolítico-Urêmica/patologia , Síndrome Hemolítico-Urêmica/virologia , Humanos , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Incidência , Rim , Necrose Tubular Aguda/sangue , Necrose Tubular Aguda/imunologia , Necrose Tubular Aguda/patologia , Necrose Tubular Aguda/virologia , Masculino , Pessoa de Meia-Idade , Nefrose Lipoide/sangue , Nefrose Lipoide/imunologia , Nefrose Lipoide/patologia , Nefrose Lipoide/virologia , Parvovirus B19 Humano/genética , Estudos Soroepidemiológicos , Viremia/sangue , Adulto JovemRESUMO
OBJECTIVES: To assess the potency of anti-viral treatment for hepatitis B virus-associated glomerulonephritis (HBV-GN). Method: We searched for controlled clinical trials on anti-viral therapy for HBV-GN in MEDLINE, Embase, the Cochrane Library, and PubMed from inception to March 11th 2019. Seven trials, including 182 patients met the criteria for evaluating. The primary outcome measures were proteinuria and changes in the estimated glomerular filtration rate, and the secondary outcome measure was hepatitis B e-antigen clearance. A fixed or random effect model was established to analyze the data. Subgroup analyses were performed to explore the effects of clinical trial type, anti-viral drug type, age, and follow-up duration. RESULTS: The total remission rate of proteinuria (OR = 10.48, 95% CI: 4.60-23.89, I2 = 0%), complete remission rate of proteinuria (OR = 11.64, 95% CI: 5.17-26.21, I2 = 23%) and clearance rate of Hepatitis Be Antigen (HBeAg) were significantly higher in the anti-viral treatment group than in the control group (OR = 27.08, 95% CI: 3.71-197.88, I2 = 63%). However, antiviral therapy was not as effective regarding the eGFR (MD = 5.74, 95% CI: -4.24-15.73). In the subgroup analysis, age and drug type had significant impacts on proteinuria remission, and study type and follow-up duration only slightly affected the heterogeneity. CONCLUSION: Antiviral therapy induced remission of proteinuria and increased HBeAg clearance but failed to improve the eGFR. Pediatric patients were more sensitive to antiviral therapy than adults. IFNs seem more effective but are accompanied by more adverse reactions than NAs.
Assuntos
Antivirais/efeitos adversos , Antivirais/farmacologia , Glomerulonefrite/virologia , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/fisiologia , Segurança , Antivirais/uso terapêutico , Glomerulonefrite/tratamento farmacológico , HumanosRESUMO
Human parvovirus B19 has been associated with various cases of kidney injuries with different glomerular phenotypes. In immunocompromised individuals, insufficient production of neutralizing antibodies can lead to chronic PVB19 carriage and manifestations. However, PVB19 DNA has been detected in bone marrow and peripheral blood for months or years in seemingly immunocompetent individuals, despite the presence of neutralizing antibodies. We report here PVB19-induced recurrent anuric acute kidney failures in a 57-year-old man over a 7-year period with persistent PVB19 infection and then PVB19-associated cryoglobulinemia. Acute renal failures were preceded by influenza-like syndrome associated with arthralgia, skin rash, and low-grade fever. Serum, bone marrow, renal, and digestive PVB19 replication was found in the different episodes. Endocapillary proliferative glomerulonephritis evolved into membranoproliferative glomerulonephritis. Complete renal recovery occurred after each bout. Off-label subcutaneous immunoglobulin therapy resulted in disappearance of blood and bone marrow PVB19 viral load and stopped the glomerulonephritis recurrence. Subcutaneous immunoglobulin therapy withdrawal resulted in renal relapse with cryoglobulin-associated manifestations.
Assuntos
Injúria Renal Aguda/prevenção & controle , Imunoglobulinas/administração & dosagem , Infecções por Parvoviridae/prevenção & controle , Parvovirus B19 Humano/isolamento & purificação , Injúria Renal Aguda/virologia , Crioglobulinemia/prevenção & controle , Crioglobulinemia/virologia , DNA Viral/análise , Glomerulonefrite/prevenção & controle , Glomerulonefrite/virologia , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Uso Off-Label , Infecções por Parvoviridae/virologia , Recidiva , Carga ViralAssuntos
Infecções por HIV/tratamento farmacológico , Hepatite B/prevenção & controle , Hepatite C/tratamento farmacológico , Falência Renal Crônica/terapia , Insuficiência Renal Crônica/terapia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Antivirais/uso terapêutico , Comorbidade , Glomerulonefrite/virologia , Infecções por HIV/epidemiologia , Unidades Hospitalares de Hemodiálise , Hepatite B/epidemiologia , Vacinas contra Hepatite B/uso terapêutico , Hepatite C/epidemiologia , Humanos , Nefropatias/virologia , Falência Renal Crônica/epidemiologia , Diálise Renal , Insuficiência Renal Crônica/epidemiologiaRESUMO
In nearly 40 years since human immunodeficiency virus (HIV) first emerged, much has changed. Our understanding of the pathogenesis of HIV infection and its effect on the cells within each kidney compartment has progressed, and the natural history of the disease has been transformed. What was once an acutely fatal illness is now a chronic disease managed with oral medications. This change is largely due to the advent of antiretroviral drugs, which have dramatically altered the prognosis and progression of HIV infection. However, the success of antiretroviral therapy has brought with it new challenges for the nephrologist caring for patients with HIV/acquired immune deficiency syndrome, including antiretroviral therapy-induced nephrotoxicity, development of non-HIV chronic kidney disease, and rising incidence of immune-mediated kidney injury. In this review, we discuss the pathogenesis of HIV infection and how it causes pathologic changes in the kidney, review the nephrotoxic effects of select antiretroviral medications, and touch upon other causes of kidney injury in HIV cases, including mechanisms of acute kidney injury, HIV-related immune complex glomerular disease, and thrombotic microangiopathy.
Assuntos
Nefropatia Associada a AIDS/virologia , Fármacos Anti-HIV/efeitos adversos , Glomerulonefrite/virologia , Infecções por HIV/tratamento farmacológico , Doenças do Complexo Imune/virologia , Microangiopatias Trombóticas/virologia , Nefropatia Associada a AIDS/etiologia , Nefropatia Associada a AIDS/genética , Nefropatia Associada a AIDS/patologia , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/etiologia , Fármacos Anti-HIV/uso terapêutico , Predisposição Genética para Doença , Glomerulonefrite/etiologia , Glomerulonefrite/imunologia , Infecções por HIV/complicações , Humanos , Doenças do Complexo Imune/etiologia , Doenças do Complexo Imune/imunologia , Insuficiência Renal Crônica/complicações , Microangiopatias Trombóticas/etiologiaRESUMO
Newer treatment protocols involving direct-acting antiviral agents (DAAs) have been associated with high rates of sustained virologic response (SVR) and clinical remission in patients with hepatitis C virus (HCV) associated cryoglobulinemic vasculitis (HCV-CV), but clinical response in those with renal involvement is less clear. Our goal was to evaluate the clinical course following DAA therapy in one of the largest cohorts of patients with HCV-associated cryoglobulinemic glomerulonephritis (HCV-GN) reported to date. This is an observational study of patients with chronic HCV infection and circulating cryoglobulins (CC) treated with DAAs in our department from January 2015 to January 2019. We identified a total of 67 patients with HCV and CC out of which nine patients fulfilled the criteria of HCV-GN and had adequate clinical follow-up time. We describe a cohort of nine patients with a mean age of 57 years and known duration of HCV infection ranging 3-20 years (four with evidence of compensated cirrhosis). All patients received the ritonavir-boosted paritaprevir/ombitasvir/dasabuvir regimen for 12 weeks and achieved SVR without subsequent viral relapse. Following DAAs completion, one patient developed "new-onset" cryoglobulinemic glomerulonephritis, six showed either persistent or worsening glomerulonephritis, and only two patients had a complete clinical response (CCR). Of the six patients with either persistent or worsening CV, 67% received additional immunosuppressive (IS) therapy for uncontrolled CV. Of the two patients that had a CCR, one patient received prior IS therapy while the other one improved without any additional intervention. Newer HCV treatment protocols involving DAAs are highly successful in eradication of HCV infection; however, in our experience, DAA treatment alone is insufficient in improving the renal outcomes of patients with HCV-GN and additional IS therapies should be considered.
Assuntos
Antivirais/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Hepatite C/complicações , Idoso , Crioglobulinemia/complicações , Crioglobulinemia/virologia , Feminino , Glomerulonefrite/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Renal inflammation significantly contributes to the progression of hepatitis B virus (HBV)-associated glomerulonephritis (HBV-GN), but the mechanisms that control its precise regulation remain largely unknown. In this study, we showed that the lysine-specific demethylase 1 (LSD1) was significantly upregulated in renal tissue of HBV-GN patients, and its expression was positively correlated with inflammation. Functionally, LSD1 could promote HBV-induced release of proinflammatory mediators in HK-2 cells, a human renal tubular epithelial (RTE) cell line. Mechanistic investigations suggested that LSD1 directly promoted the transcription of the inflammatory-related gene Tlr4 by eliminating the mono- or di-methylation of H3K9 near its promoter. Knockdown of Lsd1 further inhibited TLR4-NF-κB/JNK signaling cascades, and subsequently decreased HBV-induced production of proinflammatory mediators in HK-2 cells. Co-transfection with Tlr4-expressing plasmids counteracted these effects. Meanwhile, downregulation of abovementioned TLR4-related pathways using small-molecule inhibitors attenuated inflammation. Importantly, LSD1 inhibitor tranylcypromine (TCP) could inhibit TLR4-NF-κB/JNK signaling axis and alleviate renal inflammation in HBV transgenic mice. Taken together, our data identify LSD1 as a novel regulator of renal inflammation and as a potential therapeutic target in HBV-GN.
Assuntos
Glomerulonefrite/metabolismo , Glomerulonefrite/virologia , Vírus da Hepatite B/metabolismo , Hepatite B/metabolismo , Histona Desmetilases/metabolismo , Receptor 4 Toll-Like/metabolismo , Animais , Linhagem Celular , Glomerulonefrite/tratamento farmacológico , Hepatite B/virologia , Histona Desmetilases/antagonistas & inibidores , Histona Desmetilases/genética , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Receptor 4 Toll-Like/antagonistas & inibidores , Receptor 4 Toll-Like/genética , Transfecção , Tranilcipromina/farmacologia , Tranilcipromina/uso terapêuticoRESUMO
BACKGROUND: After allogeneic haematopoietic stem cell transplantation (allo-HSCT), Hepatitis B virus reactivation (HBVr) can be observed in patients with previous resolved Hepatitis B virus (HBV) infections. Nephrotic syndrome (NS) is the main clinical manifestation of HBsAg-positive glomerulonephritis. However, the development of HBVr combined with NS after allo-HSCT is uncommon. CASE PRESENTATION: We presented a case of a 47-year-old female with acute myelogenous leukemia who underwent HLA-identical sibling allo-HSCT and achieved leukemia free survival. She had pretransplant serological markers of a resolved HBV infection (HBsAg-negative, anti-HBc and anti-HBs positive). However, she developed HBVr combined with nephrotic syndrome (NS) 16 months after HSCT. Her histological renal lesion was mesangial proliferative glomerulonephritis. IgA+, IgM+, and C1q deposits but not HBV antigens (HBsAg and HBcAg) were identified in her renal biopsy material. Long-term entecavir and immunosuppression resulted in decrease of HBV virus replication, amelioration of proteinuria and stabilisation of renal function. CONCLUSIONS: Entecavir combined with immunosuppression has efficacy in the treatment of HBVr combined with NS after allo-HSCT, but long course of treatment is needed. Closely monitoring and antiviral prophylaxis might be necessary for allo-HSCT recipients to prevent reactivation of resolved HBV infection and its related complications.
Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatite B/tratamento farmacológico , Hepatite B/etiologia , Síndrome Nefrótica/virologia , Antivirais/uso terapêutico , Biomarcadores/sangue , Feminino , Glomerulonefrite/virologia , Guanina/análogos & derivados , Guanina/uso terapêutico , Anticorpos Anti-Hepatite B/sangue , Antígenos do Núcleo do Vírus da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/patogenicidade , Vírus da Hepatite B/fisiologia , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Síndrome Nefrótica/etiologia , Transplante Homólogo/efeitos adversos , Ativação Viral/efeitos dos fármacosRESUMO
Background: Para- and post-infectious glomerulonephritis may be caused by various microbiological agents. We present a case of parvovirus B19 infection causing a post-infectious glomerulonephritis. Case presentation: A 30-year-old woman was admitted to hospital after four weeks of fever, flank pain and general oedema. Laboratory measurements showed elevated creatinine and alanine aminotransferase, whereas haemoglobin, albumin and thrombocyte levels were low. The urine analyses were positive for both haematuria and proteinuria. Ultrasound and CT scan of the thorax and abdomen showed multiple increased lymphoid nodes, bilateral pleural effusion, periportal oedema and ascites. C3 was low, and C4 normal. Additional immunological laboratory tests were negative. Viral serology was positive for parvovirus B19 immunoglobulin M and immunoglobulin G, confirming glomerulonephritis triggered by infection. The patient's symptoms resolved without any specific treatment, and a few months later creatinine had normalised. Interpretation: This case report illustrates the importance of microbiological laboratory work-up to further investigate acute kidney failure of unknown cause.
Assuntos
Glomerulonefrite , Infecções por Parvoviridae/complicações , Parvovirus B19 Humano/isolamento & purificação , Doença Aguda , Adulto , Feminino , Glomerulonefrite/diagnóstico , Glomerulonefrite/virologia , HumanosAssuntos
Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Ganciclovir/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Glomerulonefrite/virologia , Transplante de Rim/efeitos adversos , Adulto , Glomerulonefrite/etiologia , Humanos , Masculino , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/etiologia , Resultado do TratamentoAssuntos
Antivirais/uso terapêutico , Glomerulonefrite/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Imidazóis/uso terapêutico , Sofosbuvir/uso terapêutico , Carbamatos , Glomerulonefrite/diagnóstico , Glomerulonefrite/imunologia , Glomerulonefrite/virologia , Hepacivirus/imunologia , Hepacivirus/patogenicidade , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/imunologia , Hepatite C Crônica/virologia , Interações Hospedeiro-Patógeno , Humanos , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Resultado do Tratamento , Valina/análogos & derivados , Carga ViralRESUMO
Human parvovirus B19 infection causes a variety of glomerular diseases such as post-infectious acute glomerulonephritis and collapsing glomerulopathy. Although each of these appears independently, it has not been fully determined why parvovirus B19 provokes such a variety of different glomerular phenotypes. Here, we report a 68-year-old Japanese man who showed endocapillary proliferative glomerulonephritis admixed with podocytopathy in association with parvovirus B19 infection. The patient showed acute onset of heavy proteinuria, microscopic hematuria and kidney dysfunction with arthralgia and oliguria after close contact with a person suffering from erythema infectiosum. In the kidney biopsy specimen, glomeruli revealed diffuse and global endocapillary infiltration of inflammatory cells, with some also showing tuft collapse with aberrant vacuolation, swelling, and hyperplasia of glomerular epithelial cells. Immunofluorescence revealed dense granular C3 deposition that resembled the "starry sky pattern". Intravenous glucocorticoid pulse therapy followed by oral prednisolone and cyclosporine combination therapy resulted in considerable amelioration of the kidney dysfunction and urinary abnormalities. The present case reveals that parvovirus B19 infection can induce different glomerular phenotypes even in the same kidney structure. This finding may provide hints useful for the further elucidation of the pathogenesis of parvovirus B19-induced glomerular lesions.
Assuntos
Eritema Infeccioso/patologia , Glomerulonefrite/patologia , Infecções por Parvoviridae , Proteinúria/patologia , Doença Aguda , Idoso , Eritema Infeccioso/diagnóstico , Eritema Infeccioso/virologia , Glomerulonefrite/diagnóstico , Glomerulonefrite/virologia , Humanos , Glomérulos Renais/patologia , Glomérulos Renais/virologia , Masculino , Proteinúria/diagnóstico , Proteinúria/virologiaRESUMO
To analyze the relationship between the factors related to the occurrence of HBV-GN and serum HBsAg-positive glomerulonephritis. A total of 56 patients were enrolled in the present study. All enrolled cases were divided into two groups according to whether HBsAg and/or HBcAg was present in renal kidney tissue: patients with Hepatitis B virus-associated nephritis (HBV-GN group, 30 cases) and patients with hepatitis B virus-combined nephritis (HBV-CG group, 26 cases). We sought to analyze the differences in clinical features and pathological characteristics in both groups. The rate of HBeAg positivity in the HBV-GN group was considerably increased in the HBV-CG group (P < 0.05), and the number of patients with HBsAg+HBeAg+HBcAb+ in the HBV-GN group was considerably increased in the HBV-CG group (21 cases vs 10 cases) (P < 0.05). Moreover, the number of MCD patients diagnosed by renal biopsy in the HBV-GN group was reduced compared with the HBV-CG group (1 case vs 7 cases) (P < 0.05). HBV infection and high-virus proliferation status were closely related with HBV-GN.