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1.
Infection ; 44(4): 483-90, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26792012

RESUMO

PURPOSE: BK-virus and JC-virus are the most common polyomaviridae associated with hemorrhagic cystitis in the allogeneic transplant setting. Hemorrhagic cystitis and symptomatic viruria caused by these viruses are a major cause of morbidity in patients undergoing allogeneic stem cell transplantation. METHODS: We performed a retrospective evaluation on a highly uniform study population of 73 patients receiving allogeneic stem cell transplantation. Patients were treated according to the FLAMSA-RIC-protocol, and were examined for the incidence of BK-/JC-viruria and late-onset BK-positive hemorrhagic cystitis within a two-year period. RESULTS: The occurrence of BK-viruria was correlated with published risk factors (acute GvHD, oral mucositis, donor type, conditioning, age, gender). Thirty patients (41 %) were found to excrete either BK-virus (n = 17), JC-virus (n = 3) or both (n = 10), of whom 18 patients (60 %) developed higher-grade hemorrhagic cystitis as opposed to none in the virus-negative control group. Higher grade GvHD (grade B-D) was more common in patients with viruria (p = 0.013) and also more common in patients with manifest hemorrhagic cystitis (p = 0.048). Similarly, oral mucositis was associated both with viruria (p = 0.014) and hemorrhagic cystitis (p = 0.005). Manifest cystitis but not viruria was significantly associated with male gender (p = 0.016). No significant correlation was found with age, conditioning with busulfane vs total body irradiation or related vs unrelated donor. CONCLUSIONS: Severe GvHD and oral mucositis are significantly associated with reactivation of polyomaviridae in the genitourinary-tract already at the level of asymptomatic viruria.


Assuntos
Vírus BK , Cistite , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções por Polyomavirus , Estomatite/virologia , Infecções Tumorais por Vírus , Adulto , Idoso , Cistite/mortalidade , Cistite/virologia , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/virologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/mortalidade , Infecções por Polyomavirus/virologia , Estudos Retrospectivos , Infecções Tumorais por Vírus/mortalidade , Infecções Tumorais por Vírus/virologia , Infecções Urinárias , Urina/virologia , Adulto Jovem
2.
J Virol Methods ; 191(1): 48-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23557668

RESUMO

Hepatitis E Virus (HEV) causes epidemic infections in regions of poor hygiene in the developing world. Over the last years, however, increasing numbers of autochthonous infections in industrialized countries have been described, leading to new interest in this pathogen. Currently available serological test formats to detect IgG and IgM antibodies are mainly based on bacterially expressed ORF2 and ORF3 antigens and often give ambiguous results. The objective of this study was the development of a different assay format for HEV diagnosis--a HEV immunofluorescence test (HEV-IFT) based on mammalian cells transiently expressing recombinant HEV ORF2 protein with a simple production and staining protocol and the investigation of its performance and methodical feasibility under diagnostic laboratory conditions. 31 sera of patients at different phases of HEV infection and 40 control sera from a non-endemic region were analyzed for anti-HEV IgG, IgM, and IgA antibodies. The HEV-IFT detected successfully anti-HEV IgG and IgA, but not anti-HEV IgM antibodies. In the study group the HEV-IFT was able to confirm HEV infections and to support diagnosis when ambiguous results were obtained by commercial assays. Signal localization and staining patterns helped to gather additional information about reactive antibodies present in patient sera. In conclusion the developed IFT for the detection of anti-HEV IgG and IgA antibodies can be used for diagnosis and for the serological confirmation of HEV infections.


Assuntos
Técnicas de Laboratório Clínico/métodos , Anticorpos Anti-Hepatite/sangue , Vírus da Hepatite E/imunologia , Hepatite E/diagnóstico , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Técnica Indireta de Fluorescência para Anticorpo/métodos , Humanos
3.
Virol J ; 7: 165, 2010 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-20646309

RESUMO

BACKGROUND: Varicella-Zoster virus causes chickenpox upon primary infection and shingles after reactivation. Currently available serological tests to detect VZV-specific antibodies are exclusively based on antigens derived from VZV-infected cells. RESULTS: We present a systematic approach for the identification of novel, serologically reactive VZV antigens. Therefore, all VZV open reading frames were cloned into a bacterial expression vector and checked for small scale recombinant protein expression. Serum profiling experiments using purified VZV proteins and clinically defined sera in a microarray revealed 5 putative antigens (ORFs 1, 4, 14, 49, and 68). These were rearranged in line format and validated with pre-characterized sera. CONCLUSIONS: The line assay confirmed the seroreactivity of the identified antigens and revealed its suitability for VZV serodiagnostics comparable to commercially available VZV-ELISA. Recombinant ORF68 (gE) proved to be an antigen for high-confidence determination of VZV serostatus. Furthermore, our data suggest that a serological differentiation between chickenpox and herpes zoster may be possible by analysis of the IgM-portfolio against individual viral antigens.


Assuntos
Antígenos Virais/sangue , Varicela/sangue , Herpes Zoster/sangue , Herpesvirus Humano 3/imunologia , Análise em Microsséries/métodos , Testes Sorológicos/métodos , Anticorpos Antivirais/sangue , Antígenos Virais/genética , Antígenos Virais/imunologia , Varicela/imunologia , Varicela/virologia , Expressão Gênica , Herpes Zoster/imunologia , Herpes Zoster/virologia , Herpesvirus Humano 3/genética , Imunoglobulina M/sangue , Fases de Leitura Aberta , Proteínas Virais/imunologia
4.
Virol J ; 7: 54, 2010 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-20205920

RESUMO

Here we report the case of a 54-year old, immunocompetent German patient with primary varicella whose Varicella-Zoster Virus (VZV)-specific T-cell responses could be detected early in infection and before the onset of seroconversion. This case demonstrates that the detection of VZV-specific T-cells may under certain circumstances support the diagnosis of a primary varicella infection, as for example in cases of atypical or subclinical varicella or in the absence of detectable VZV DNA in plasma.


Assuntos
Anticorpos Antivirais/sangue , Varicela/diagnóstico , Varicela/imunologia , Herpesvirus Humano 3/imunologia , Linfócitos T/imunologia , DNA Viral/sangue , Alemanha , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo
6.
Blood ; 115(14): 2960-70, 2010 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-20103780

RESUMO

Posttransplantation lymphoproliferative disease (PTLD) associated with Epstein-Barr virus (EBV) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation. PTLD is efficiently prevented by adoptive transfer of EBV-specific T cells from the donor. To make EBV-specific T cells available in urgent clinical situations, we developed a rapid protocol for their isolation by overnight stimulation of donor blood cells with peptides derived from 11 EBV antigens, interferon-gamma surface capture, and immunomagnetic separation. Six patients with PTLD received 1 transfusion of EBV-specific T cells. No response was seen in 3 patients who had late-stage disease with multiorgan dysfunction at the time of T-cell transfer. In 3 patients who received T cells at an earlier stage of disease, we observed complete and stable remission of PTLD. Two patients have remained free from EBV-associated disease for more than 2 years. CD8(+) T cells specific for EBV early antigens rapidly expanded after T-cell transfer, temporarily constituted greater than 20% of all peripheral blood lymphocytes, and were maintained throughout the observation period. Thus, a rapid and sustained reconstitution of a protective EBV-specific T-cell memory occurred after the infusion of small numbers of directly isolated EBV-specific T cells.


Assuntos
Antígenos Virais/farmacologia , Infecções por Vírus Epstein-Barr/terapia , Herpesvirus Humano 4 , Transfusão de Linfócitos , Transtornos Linfoproliferativos/imunologia , Transtornos Linfoproliferativos/terapia , Peptídeos/farmacologia , Linfócitos T/transplante , Proteínas Virais/farmacologia , Adulto , Anemia Aplástica/imunologia , Anemia Aplástica/terapia , Anemia Aplástica/virologia , Antígenos Virais/imunologia , Infecções por Vírus Epstein-Barr/imunologia , Feminino , Humanos , Memória Imunológica , Interferon gama , Leucaférese/métodos , Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Leucemia Mieloide Aguda/virologia , Linfoma de Células T/imunologia , Linfoma de Células T/terapia , Linfoma de Células T/virologia , Masculino , Pessoa de Meia-Idade , Peptídeos/imunologia , Indução de Remissão , Transplante de Células-Tronco , Linfócitos T/imunologia , Transplante Homólogo , Proteínas Virais/imunologia
7.
NDT Plus ; 2(2): 149-51, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25949314

RESUMO

Cytomegalovirus (CMV) infection after renal transplantation is a problem of increasing concern resulting in significant morbidity and mortality. Widespread use of ganciclovir (GCV) and valganciclovir (VGCV) may cause an increase of CMV resistance to these first line drugs. Other treatment options are sparse and often complicated by adverse events, namely nephrotoxicity associated with foscarnet and cidofovir. Leflunomide may be another treatment option for CMV infections. So far it is not clear if leflunomide can also be used in the case of GCV-resistant CMV infections. Here we describe the use of leflunomide in two patients after renal transplantation with GCV-resistant CMV infections.

8.
J Clin Virol ; 34(3): 219-23, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16129661

RESUMO

Cytomegalovirus (CMV) positive recipients of CMV negative bone marrow bear a significantly higher risk of developing CMV disease compared to all other constellations. Here, we report a case of severe CMV induced esophagitis after allogeneic bone marrow transplantation for paroxysmal nocturnal hemoglobinuria. The patient developed the first symptoms between day 10 and 20 after dose reduced conditioning and HLA-matched unrelated stem cell transplantation. Esophageal tissue biopsies as well as peripheral blood proved positive for CMV DNA by PCR. Treatment with acyclovir, ganciclovir, foscarnet, cidofovir, and immunoglobulines resulted in elimination of CMV in peripheral blood but not in clinical improvement. Only tapering of cyclosporine at day +120 eventually led to the development of CMV-specific T-cells and resolution of esophagitis.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/etiologia , Esofagite/etiologia , Imunossupressores/efeitos adversos , Condicionamento Pré-Transplante/métodos , Antivirais/uso terapêutico , Quimioterapia Combinada , Esofagite/tratamento farmacológico , Feminino , Hemoglobinúria Paroxística/complicações , Hemoglobinúria Paroxística/terapia , Humanos , Pessoa de Meia-Idade , Linfócitos T/imunologia , Transplante Homólogo
9.
Clin Infect Dis ; 40(6): 887-9, 2005 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-15736025

RESUMO

Human herpesvirus 6 (HHV-6), the causative agent of exanthema subitum in childhood, can also induce meningoencephalitis in immunocompromised individuals. In contrast, HHV-6 encephalitis in immunocompetent patients is rare, and the clinical syndrome not well defined. We report a case of meningoencephalitis caused by HHV-6 type B in an otherwise healthy woman.


Assuntos
Ganciclovir/uso terapêutico , Herpesvirus Humano 6/fisiologia , Imunocompetência , Meningoencefalite/tratamento farmacológico , Meningoencefalite/virologia , Infecções por Roseolovirus/virologia , Adulto , Antivirais/uso terapêutico , Feminino , Herpesvirus Humano 6/isolamento & purificação , Humanos , Meningoencefalite/diagnóstico , Infecções por Roseolovirus/diagnóstico , Infecções por Roseolovirus/tratamento farmacológico
10.
Pediatr Transplant ; 7(1): 46-52, 2003 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-12581328

RESUMO

We tested blood samples of 25 pediatric renal transplant recipients for Epstein-Barr virus (EBV) DNA load by quantitative polymerase chain reaction (PCR). Eleven of these transplant recipients showed clinical persistent mononucleosis-like symptoms years after transplantation (Tx). A quantitation of EBV DNA by PCR in peripheral blood lymphocyte (PBL) and serum samples revealed variable EBV DNA titers. The majority of EBV PCR results in samples of the 14 asymptomatic transplant recipients was repeatedly below detection limit. In contrast, patients with mononucleosis-like symptoms showed persistent EBV genome titers over a period of 6 months, ranging from 75 to 18 750 copies/10 000 PBL and from 680 to 335 000 copies/mL serum, respectively. One child suffering from this mononucleosis-like condition developed an EBV-associated Burkitt-like lymphoma 29 months after Tx. Whereas clinical and histological investigations did not indicate a post-transplant lymphoproliferative disorder (PTLD) until tumor detection, EBV titers in PBL and serum had been high for at least 8 months. We propose that pediatric transplant recipients who show both, recurrent mononucleosis-like symptoms and a sustained high EBV genome load, are at increased risk for severe EBV-related post-transplant complications.


Assuntos
DNA Viral/sangue , Herpesvirus Humano 4/isolamento & purificação , Mononucleose Infecciosa/diagnóstico , Transplante de Rim/efeitos adversos , Leucócitos/virologia , Transtornos Linfoproliferativos/etiologia , Linfoma de Burkitt/diagnóstico , Linfoma de Burkitt/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Mononucleose Infecciosa/etiologia , Mononucleose Infecciosa/transmissão , Masculino , Reação em Cadeia da Polimerase , Fatores de Risco
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