Browse
Submit Data
Databases
API
Help

Dataset Information

11 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Late-onset severe chronic active EBV in a patient for five years with mutations in STXBP2 (MUNC18-2) and PRF1 (perforin 1).

ABSTRACT: Severe chronic active Epstein-Barr virus (CAEBV) disease is defined as a severe progressive illness lasting 6 months or longer with infiltration of tissues with EBV-positive lymphocytes, markedly elevated levels of EBV DNA in the blood, and no known immunodeficiency such as HIV. These patients usually have fever, splenomegaly, lymphadenopathy, and may have markedly elevated EBV antibody titers to viral capsid antigen. Although the cause of most cases of severe CAEBV is unknown, one well-documented case was associated with compound heterozygous mutations in PRF1 (perforin 1). Here we report a patient with prolonged severe CAEBV who underwent bone marrow transplant for his disease and subsequently was found to have compound heterozygous mutations in STXBP2 (MUNC18-2) as well as a heterozygous mutation in PRF1 (perforin 1).

SUBMITTER: Cohen JI

PROVIDER: S-EPMC4504756 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Late-onset severe chronic active EBV in a patient for five years with mutations in STXBP2 (MUNC18-2) and PRF1 (perforin 1).

Cohen Jeffrey I JI Niemela Julie E JE Stoddard Jennifer L JL Pittaluga Stefania S Heslop Helen H Jaffe Elaine S ES Dowdell Kennichi K

Journal of clinical immunology 20150507 5

Severe chronic active Epstein-Barr virus (CAEBV) disease is defined as a severe progressive illness lasting 6 months or longer with infiltration of tissues with EBV-positive lymphocytes, markedly elevated levels of EBV DNA in the blood, and no known immunodeficiency such as HIV. These patients usually have fever, splenomegaly, lymphadenopathy, and may have markedly elevated EBV antibody titers to viral capsid antigen. Although the cause of most cases of severe CAEBV is unknown, one well-document ...[more]

PMID: 25947952

Similar Datasets

Hypomorphic mutations in PRF1, MUNC13-4, and STXBP2 are associated with adult-onset familial HLH.

Project description:Familial hemophagocytic lymphohistiocytosis (HLH) is a rare primary immunodeficiency disorder characterized by defects in cell-mediated cytotoxicity that results in fever, hepatosplenomegaly, and cytopenias. Familial HLH is well recognized in children but rarely diagnosed in adults. We conducted a retrospective review of genetic and immunologic test results in patients who developed HLH in adulthood. Included in our study were 1531 patients with a clinical diagnosis of HLH; 175 patients were 18 years or older. Missense and splice-site sequence variants in PRF1, MUNC13-4, and STXBP2 were found in 25 (14%) of the adult patients. The A91V-PRF1 genotype was found in 12 of these patients (48%). The preponderance of hypomorphic mutations in familial HLH-causing genes correlates with the later-onset clinical symptoms and the more indolent course in adult patients. We conclude that late-onset familial HLH occurs more commonly than was suspected previously.

| S-EPMC3228496 | biostudies-literature

Perforin gene PRF1 c.900C> T polymorphism and HIV-1 vertical transmission.

Project description:Perforin-1, a component of the immune system, is able to control Human Immunodeficiency Virus-1 (HIV-1) replication and could be involved in HIV-1 mother-to-child transmission (MTCT). This study aims at evaluating the role of the c.900C > T PRF1 gene (encoding for perforin-1) polymorphism (rs885822) in HIV-1 MTCT. The PRF1 c.900C > T polymorphism was genotyped in 331 children from Zambia using a Taqman probe on a Real Time PCR platform. The PRF1 c.900C > T C/T genotype was more frequent among HIV-1 exposed but non-infected children than in HIV-1 positive cases, and the results were confirmed among children infected during breastfeeding. PRF1 c.900C > T correlated with protection against HIV-1 MTCT, suggesting its role in HIV-1 vertical transmission.

| S-EPMC6905447 | biostudies-literature

Perforin-deficient CAR T cells recapitulate late-onset inflammatory toxicities observed in patients.

Project description:Late-onset inflammatory toxicities resembling hemophagocytic lymphohistiocytosis (HLH) or macrophage activation syndrome (MAS) occur after chimeric antigen receptor T cell (CAR T cell) infusion and represent a therapeutic challenge. Given the established link between perforin deficiency and primary HLH, we investigated the role of perforin in anti-CD19 CAR T cell efficacy and HLH-like toxicities in a syngeneic murine model. Perforin contributed to both CD8+ and CD4+ CAR T cell cytotoxicity but was not required for in vitro or in vivo leukemia clearance. Upon CAR-mediated in vitro activation, perforin-deficient CAR T cells produced higher amounts of proinflammatory cytokines compared with WT CAR T cells. Following in vivo clearance of leukemia, perforin-deficient CAR T cells reexpanded, resulting in splenomegaly with disruption of normal splenic architecture and the presence of hemophagocytes, which are findings reminiscent of HLH. Notably, a substantial fraction of patients who received anti-CD22 CAR T cells also experienced biphasic inflammation, with the second phase occurring after the resolution of cytokine release syndrome, resembling clinical manifestations of HLH. Elevated inflammatory cytokines such as IL-1β and IL-18 and concurrent late CAR T cell expansion characterized the HLH-like syndromes occurring in the murine model and in humans. Thus, a murine model of perforin-deficient CAR T cells recapitulated late-onset inflammatory toxicities occurring in human CAR T cell recipients, providing therapeutically relevant mechanistic insights.

| S-EPMC7524496 | biostudies-literature

Late onset Descemet's membrane detachment 20 years after penetrating keratoplasty.

Project description:This paper reports a case of spontaneous Descemet's Membrane (DM ) detachment 20-years after penetrating keratoplasty (PK). The patient presented with acute onset blurred vision in the right eye associated with mild ocular discomfort. There was no prior history of trauma. The patient had undergone PK in the right eye 20 years back. Detailed ophthalmic examination showed best corrected visual acuity of hand movements close to face in the right eye and 20/80 in the left eye. The right eye showed diffuse graft edema but no congestion, epithelial defect, or loss of continuity of graft-host junction to suggest a traumatic etiology. Anterior segment optical coherence tomography showed DM break with a detachment in the right eye, which was treated with an intracameral C3F8 injection. DM break with detachment post-PK has been very sparsely reported in literature and is an important differential to remember when faced with an edematous graft, in addition to the diagnosis of graft rejection or failure.

| S-EPMC5549419 | biostudies-other

Microarray expression analysis of PRF1 (perforin 1) haplotypes in patients with primary progressive multiple sclerosis

Project description:A genetic study of the PRF1 gene has shown association of several polymorphisms with multiple sclerosis (MS). Haplotype analysis identified risk haplotypes strongly associated with male patients having the primary-progressive form of MS (PPMS). Gene expression microarrays were performed in 10 male PPMS patients carrying the risk (n=6) and protective haplotypes (n=4) in order to identify pathways associated with the risk haplotypes. Pathway analysis revealed overrepresentation of the cell killing gene ontology category among down-regulated genes in patients carrying risk haplotypes compared with patients carrying protective haplotypes.

2010-07-28 | GSE23205 | GEO

Late Onset of Primary Hemophagocytic Lymphohistiocytosis (HLH) with a Novel Constellation of Compound Heterozygosity Involving Two Missense Variants in the <i>PRF1</i> Gene.

Project description:Hemophagocytic lymphohistiocytosis (HLH) is a rare but in most cases life-threatening immune-mediated disease of the hematopoietic system frequently associated with hematologic neoplasms. Here, we report on a case in which we detected a novel constellation of two missense variants affecting the PRF1 gene, leading to de novo primary HLH. Diagnostics included a comprehensive clinical work-up and standard methods of hematopathology as well as extended molecular genomics based on polymerase chain reaction (PCR) reactions and the calculation of three-dimensional molecule reconstructions of PRF1. Subsequently, a comprehensive review of the literature was performed, which showed that this compound heterozygosity has not been previously described. The patient was a 20-year-old female. Molecular diagnostics revealed two heterozygous missense variants in the PRF1 gene (A91V and R104C) on exon 2. Apart from the finding of two inconclusive genetic variants, all clinical criteria defined by the HLH study group of Histiocyte Society were met at initial presentation. The final diagnosis was made in cooperation with the Consortium of German HLH-reference centers. Here, chemotherapy did not lead to sufficient sustained disease control. Therefore, the decision for allogenic hematopoietic stem cell transplantation (alloHSCT) was made. Hitherto, the duration of response was 6 months. Due to severe and unmanageable hepatic graft-versus-host disease (GvHD), the patient died. We report on a novel constellation of a compound heterozygosity containing two missense variants on exon 2 of the PRF1 gene. To the authors' best knowledge, this is the first presentation of a primary HLH case harboring this genomic constellation with late-onset clinical manifestation.

| S-EPMC10931657 | biostudies-literature

Recurrent subacute post-viral onset of ataxia associated with a PRF1 mutation.

Project description:Inflammation is an important contributor to pediatric and adult neurodegeneration. Understanding the genetic determinants of neuroinflammation provides valuable insight into disease mechanism. We characterize a disorder of recurrent immune-mediated neurodegeneration. We report two sisters who presented with neurodegeneration triggered by infections. The proband, a previously healthy girl, presented at 22.5 months with ataxia and dysarthria following mild gastroenteritis. MRI at onset showed a symmetric signal abnormality of the cerebellar and peritrigonal white matter. Following a progressive course of partial remissions and relapses, she died at 5 years of age. Her older sister had a similar course following varicella infection, she died within 13 months. Both sisters had unremarkable routine laboratory testing, with exception of a transient mild cytopenia in the proband 19 months after presentation. Exome sequencing identified a biallelic perforin1 mutation (PRF1; p.R225W) previously associated with familial hemophagocytic lymphohistiocytosis (FHL). In contrast to FHL, these girls did not have hematopathology or cytokine overproduction. However, 3 years after disease onset, the proband had markedly deficient interleukin-1 beta (IL-1?) production. These observations extend the spectrum of disease associated with perforin mutations to immune-mediated neurodegeneration triggered by infection and possibly due to primary immunodeficiency.

| S-EPMC3798831 | biostudies-other

Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

Project description:Connexin26 (Cx26, GJB2) mutations account for >50% of nonsyndromic hearing loss. The deafness is not always congenital. A large group of these patients (∼30%) demonstrate a late-onset hearing loss, starting in childhood. They have normal hearing early in life and are therefore good candidates for applying protective and therapeutic interventions. However, the underlying deafness mechanism is unclear. In this study, we used a time-controlled, inducible gene knockout technique to knockout Cx26 expression in the cochlea after birth. We found that deletion of Cx26 after postnatal day 5 (P5) in mice could lead to late-onset hearing loss. Similar to clinical observations, the mice demonstrated progressive, mild to moderate hearing loss. The hearing loss initiated at high frequencies and then extended to the middle- and low-frequency range. The cochlea showed normal development and had no apparent hair cell loss. However, distortion product otoacoustic emission (DPOAE) was reduced. The reduction was also progressive and large at high-frequencies. Consistent with DPOAE reduction, we found that outer hair cell electromotility-associated nonlinear capacitance was shifted to the right and the slope of voltage dependence was reduced. The endocochlear potential was reduced in Cx26 conditional knockout (cKO) mice but the reduction was not associated with progressive hearing loss. These data suggest that Cx26 deficiency may impair active cochlear amplification leading to late-onset hearing loss. Our study also helps develop newer protective and therapeutic interventions to this common nonsyndromic hearing loss.

| S-EPMC4268423 | biostudies-literature

Chronic active EBV cases

Project description:EBV deletions as biomarkers of response to treatment of Chronic Active Epstein Barr Virus

| PRJEB41945 | ENA

Gene expression profiling identifies a gene signature that predicts progression to active tuberculosis several years before disease onset

Project description:We evaluated the predictive ability of various gene signatures in baseline peripheral blood mononuclear cell samples to distinguish Mtb-infected individuals who eventually progress to TB disease (progressors) or who remain asymptomatic (non-progressors) during clinical follow-up; we also compare long-term Mtb-infected non-progressors from patients with TB disease

2020-02-25 | GSE112104 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data