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Query: UMLS:C0021345 (infectious mononucleosis)
 3,358 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Three families with X-linked lymphoproliferative disease were studied. Affected males clinically presented with severe or fatal infectious mononucleosis, acquired hypogammaglobulinaemia, hypergammaglobulinaemia M, and malignant lymphoma including Hodgkin disease. Haplotype analysis using various DNA markers from Xq25-q27 allowed the prediction of the carrier status in females and identification of the XLP status in asymptomatic males.
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PMID:Molecular genetic haplotype segregation studies in three families with X-linked lymphoproliferative disease. 791 89

Infectious mononucleosis is a well-established clinical entity characterized by the proliferation of B lymphocytes that are infected with Epstein-Barr virus (EBV). These lymphocytes give rise to an increase in specifically reacting cytotoxic T cells, which leads to self-limitation of the lympho-proliferative process. We describe the case of a 1-year-old boy who developed life-threatening EBV infection in association with liver failure, depletion of bone marrow, and severe encephalitis. The fact that clinical cure was achieved when acyclovir (50 mg/[kg.d]) and prednisolone (1 mg/[kg.d]) were administered indicates a correlation between antiviral therapy and clinical improvement. Hypogammaglobulinemia--which had not been present at the onset of disease--persisted after clinical recovery. During the acute phase of the illness, the patient's blood lymphocytes were predominantly T cells, most of which contained the EBV genome, as shown by in situ hybridization; some of these cells stained positive for EBV-specific latent membrane protein. Examination of peripheral blood mononuclear cells in vitro revealed an exceedingly high histocompatibility antigen-unrestricted cytotoxicity against the K562 cell line, which is normally not an immunogenic target of cytotoxic cells in patients infected with EBV. This anomalous natural killer cell-like T cell function suggests that EBV infection of T cells might cause auto-aggressive activity, which was probably responsible for the severity of the infection in our patient.
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PMID:Life-threatening infectious mononucleosis: is it correlated with virus-induced T cell proliferation? 794 20

It has been postulated that human cytomegalovirus (HCMV) infection may have a role in the pathogenesis of common variable immunodeficiency (CVID). Many patients have a lymphocyte phenotype similar to that seen in HCMV infection, HCMV mononucleosis may precipitate hypogammaglobulinaemia, and a previous small study of common variable immunodeficient patients reported a high rate of active HCMV infection. This study investigated the presence and activity of HCMV infection in 102 CVID patients. Buffy coats were examined for the presence of HCMV IE and glycoprotein B genes using highly sensitive nested PCR. 30 blood donors of known HCMV serologic status were used as controls. There was no significant difference in HCMV positivity by PCR between patients and controls. Enrichment for mononuclear cells prior to PCR had no effect on sensitivity. Twenty-five patients were also examined for HCMV antigenaemia by staining buffy coat cytospins with monoclonal antibodies directed against the HCMV pp65 lower matrix protein, a technique widely used for diagnosis of active HCMV disease. Only one patient was positive (and also positive by PCR). Whilst these results do not exclude prior infection contributing to antibody deficiency in a small proportion of CVID patients, this study refutes the previously reported increase in active HCMV infection in CVID.
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PMID:Human cytomegalovirus infection is not increased in common variable immunodeficiency. 888 96

We report the occurrence of X-linked lymphoproliferative disease (XLP) in two brothers in a Malaysian family. In this disorder, a primary Epstein-Barr virus (EBV) infection is followed by an abnormal proliferation of transformed B-cells that cannot be controlled by suppressor T-cells, leading to the development of deranged immune function. This results in fatal infectious mononucleosis, acquired hypogammaglobulinaemia, virus-infected haemophagocytic syndrome and non-Hodgkin's lymphoma. The diagnosis should be considered when there is a family history of any male having a fulminant course of infectious mononucleosis, an otherwise benign disease. Early diagnosis is important as bone marrow transplantation is the only curative option in this disorder.
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PMID:Two brothers in a Malaysian family with X-linked lymphoproliferative disease--a case report. 894 43

X-linked lymphoproliferative disease (XLP) is characterized by a marked vulnerability to Epstein-Barr virus (EBV) infection. Infection of XLP patients with EBV invariably results in fatal mononucleosis, agammaglobulinemia, or malignant lymphoma. Initially the XLP gene was assigned to a 10-cM region in Xq25 between DXS42 and DXS37. Subsequently, an interstitial, cytogenetically visible deletion in Xq25 was identified in one XLP family, 43. In this study we estimated the deletion in XLP patient 43-004 by dual-laser flow karyotyping to involve 2% of the X chromosome, or approximately 3 Mb of DNA sequence. From a human chromosome Xq25-specific yeast artificial chromosome (YAC) sublibrary, five YACs containing DNA sequences deleted in patient 43-004 have been isolated. Sequence-tagged sites (STSs) from these YACs have been used to identify interstitial deletions in unrelated XLP patients. Three more families with interstitial deletions were found. Two of the patients (63-003 and 73-032) carried an interstitial deletion of 3.0 Mb overlapping the 43-004 deletion. In one XLP patient (30-011) who exhibited the characteristic postinfectious mononucleosis phenotype of XLP with hypogammaglobulinemia and malignant lymphoma, a deletion of approximately 250 kb was detected overlapping the deletion detected in patients 43-004, 63-003, and 73-032. A YAC contig of 2.2 Mb spanning the XLP critical region, whose orientation on chromosome X was determined by double-color fluorescence in situ hybridization and which consists of 15 overlapping YAC clones, has been constructed. A detailed restriction enzyme map of the region has been constructed. YAC insert sizes were determined by counter-clamped homogenous electric field gel electrophoresis. Chimerism of YACs was determined by FISH and restriction mapping. On the basis of lambda subclones, YAC end-derived plasmids, and STSs with an average spacing of 100 kb, a long-range physical map was constructed using 5 rare-cutter restriction enzymes. The STSs and lambda subclones were used in Southern hybridization and PCR analyses. The work presented here substantially refines the critical region for XLP. The YAC contig with the overlapping interstitial deletions constitutes the basis for the construction of a transcriptional map of the critical region and facilitates the identification of the XLP gene.
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PMID:A yeast artificial chromosome (YAC) contig encompassing the critical region of the X-linked lymphoproliferative disease (XLP) locus. 902 86

X-linked lymphoproliferative syndrome (XLP or Duncan disease) is characterized by extreme sensitivity to Epstein-Barr virus (EBV), resulting in a complex phenotype manifested by severe or fatal infectious mononucleosis, acquired hypogammaglobulinemia and malignant lymphoma. We have identified a gene, SH2D1A, that is mutated in XLP patients and encodes a novel protein composed of a single SH2 domain. SH2D1A is expressed in many tissues involved in the immune system. The identification of SH2D1A will allow the determination of its mechanism of action as a possible regulator of the EBV-induced immune response.
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PMID:Host response to EBV infection in X-linked lymphoproliferative disease results from mutations in an SH2-domain encoding gene. 977 93

X-linked lymphoproliferative disease (XLP) is a rare familial disorder resulting in selective immunodeficiency to the Epstein-Barr virus (EBV), characterized by uncontrolled proliferation of EBV-infected lymphocytes. Phenotypes of this disease are variable and include fulminant infectious mononucleosis, hypogammaglobulinemia, and malignant lymphoma. In this article, we describe a case of a previously healthy 4-year-old boy with serologic evidence of acute EBV infection who died of fulminant hepatic failure. Histopathological examination of tissue obtained postmortem showed hemophagocytosis and prominent polymorphous infiltrates associated with necrosis in the liver, spleen, and lymph nodes. Semiquantitative polymerase chain reaction (PCR) utilizing primers complementary to the EBV gene LMP2a performed on samples of liver tissue demonstrated approximately 0.6 copies of the EBV gene per cell. Immunohistochemistry demonstrated light chain restriction and PCR studies of the immunoglobulin V-D-J region revealed two strong bands, consistent with a clonal B cell proliferation. Extended family history revealed that the boy's family was followed by the XLP Registry, which was established in 1978 to follow kindreds with XLP. The genetic abnormality associated with XLP has been localized to the Xq25, allowing RFLP analysis to identify female carriers and affected boys.
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PMID:X-linked lymphoproliferative disease: pathology and diagnosis. 984 10

The X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by an abnormal responses to infection with Epstein-Barr virus (EBV), resulting in fatal infectious mononucleosis, hypogammaglobulinemia, virus-associated hemophagocytic syndrome, and malignant lymphoma. Mutations in the gene coding for a T cell-specific SLAM-associated protein (SAP) have been recently identified in XLP patients. We report on a 1-year-old boy representing fulminant hemophagocytic syndrome. He developed high fever, lymphadenopathy, hepatosplenomegaly with liver dysfunction, and pancytopenia with marrow hemophagocytosis. EBV DNA was abnormally increased in the blood. Polymerase chain reaction failed to amplify SAP mRNA and genomic DNA products from the patient' As peripheral blood. A large deletion of the SAP gene was confirmed by fluorescence in situ hybridization (FISH). FISH analysis also disclosed that the patient's mother was a carrier. We conclude that FISH can be useful in the diagnosis of XLP with large deletions of the SAP gene and its carrier state.
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PMID:Large deletion of the X-linked lymphoproliferative disease gene detected by fluorescence in situ hybridization. 1081 94

X-linked lymphoproliferative disease (XLP), a genetic disorder characterized by immunodeficiency to Epstein-Barr virus (EBV) infection, has been linked to mutations in the SH2D1A gene. To search for the occurrence of SH2D1A mutations in Japan, we performed genetic analysis of the SH2D1A gene in 40 males presenting with severe EBV-associated illnesses, including fulminant infectious mononucleosis, EBV-positive lymphoma, and severe chronic active EBV infection. SH2D1A mutations were detected in 10 of these 40 patients. Five of these 10 cases were sporadic. Patients with SH2D1A mutations displayed severe acute infectious mononucleosis with hyperimmunoglobulin M, hypogammaglobulinemia, and B-cell malignant lymphoma. By contrast, chronic active EBV infection was not associated with SH2D1A mutations. XLP survivors exhibited normal levels of circulating EBV-DNA during convalescence, suggesting that SH2D1A protein is not directly responsible for control of EBV replication. Thus, genetic analysis of the SH2D1A gene is particularly useful in the diagnosis of sporadic cases and carriers of XLP. (Blood. 2001;98:1268-1270)
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PMID:SH2D1A mutations in Japanese males with severe Epstein-Barr virus--associated illnesses. 1149 83

X-linked lymphoproliferative disease (XLP) is an inherited immunodeficiency characterized by extreme vulnerability to Epstein-Barr virus (EBV) infection, resulting in fatal infectious mononucleosis, dysgammaglobulinemia and malignant lymphoma. Recently, mutations in the SH2D1A gene, which encodes SLAM-associated protein (SAP), have been found to cause XLP. Although the molecular events behind XLP are largely unknown, there is evidence that affected males exhibited some immunohematological abnormalities, such as hypogammaglobulinemia or lymphoma, even prior to EBV infection. Because of the poor prognosis in XLP, an early diagnosis to patients and families is clinically of great importance. A glutathione-S-transferase-SAP fusion protein was used to immunize rats and generate mAb against human SAP to investigate its pathogenic role in XLP and develop a flow cytometric assay for detection of XLP. By flow cytometric and Western immunoblot analyses using an established anti-SAP mAb, termed KST-3, we determined that SAP was expressed intensely in thymocytes, but at lower levels in peripheral T cells and NK cells. In contrast, expression of SAP was negligible in B cells, monocytes or granulocytes. We found that SAP expression in T cells increased upon in vivo as well as in vitro activation. In two XLP survivors with SH2D1A mutations, a flow cytometric evaluation of activated T cells using KST-3 could demonstrate SAP deficiency as a diagnostic indicator of XLP. Through this approach, we identified three novel XLP families with SH2D1A mutations in Japan. A flow cytometric assessment of SAP expressed in activated T cells would lead to easy detection of XLP patients.
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PMID:Activation-dependent T cell expression of the X-linked lymphoproliferative disease gene product SLAM-associated protein and its assessment for patient detection. 1235 86


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