Epstein-Barr virus (EBV) is the pathogen that most commonly triggers infection-associated hemophagocytic lymphohistiocytosis (HLH) and ectopically infects CD8(+) T cells in EBV-associated HLH (EBV-HLH). We recently described an EBV-HLH patient who had a clonally expanded population of EBV-infected CD8(+) T cells with CD5 down-regulation. To determine whether this finding could serve as a useful marker for EBV-HLH, we investigated 5 additional patients. We found a significant increase in the subpopulation of CD8(+) T cells with CD5 down-regulation and bright human leukocyte antigen (HLA)-DR expression in all patients with EBV-HLH but not in patients with infectious mononucleosis or in control subjects. Such T cells were frequently found to be larger cells that stained positive for a specific T cell receptor VB. We also demonstrated that those cells were the major cellular target of EBV, and their numbers progressively declined in parallel with the serum ferritin levels. All together, our findings reveal the immunophenotypic characteristics of EBV-infected CD8(+) T cells and may provide a valuable tool for the diagnosis of EBV-HLH.

No abstract

No abstract

In chronic active Epstein-Barr virus (EBV) infection (CAEBV), ectopic EBV infection has been described in T or natural killer (NK) cells. NK cell-type infection (NK-CAEBV) is characterized by large granular lymphocytosis, high IgE levels, and unusual reactions to mosquito bites, including severe local skin reactions, fever and liver dysfunction. However, the mechanisms underlying these reactions remain

No abstract

No abstract

Most reported cases of familial Mediterranean fever (FMF) involve missense mutations of MEFV concentrated within exon 10. We experienced two independent pedigrees of a unique variant in the MEFV gene that might cause excessive exon 2 skipping due to enhanced alternative splicing. In this study, we tried to elucidate the molecular mechanism of the MEFV variant as a cause of the FMF phenotype. Peripheral blood was obtained from volunteers and two patients with homozygous c.910G>A variant of the MEFV gene. MEFV messenger RNA (mRNA) expression patterns in mononuclear cells and granulocytes were compared using forward and reverse primers from exons 1 and 3, respectively. Expression profiles of pyrin were examined by transfecting wild-type and variant MEFV genes into HEK293T cells. Expression of normal-sized mRNA was extremely reduced in these patients, whereas that of aberrant short mRNA, deleting exon 2 (Δex2), was significantly increased. Immunohistochemical and immunoblotting analyses revealed a truncated immunoreactive pyrin protein in cells transfected with Δex2 cDNA. The MEFV gene c.910G>A variant results in accelerated aberrant splicing with abnormal protein size, presumably leading to anomalous pyrin function. This is the first report to show that an MEFV variant other than missense mutation is responsible for the FMF phenotype.

This report describes a 2-year-old girl with congenitally corrected transposition of the great arteries (ccTGA) who presented with transient complete atrioventricular (AV) block after a mild chest blow. Running around the house with her older sister, she fell to the floor. Her sister also fell and landed on her. The girl became cyanotic and pale and experienced a transient loss of consciousness. At arrival to the emergency department, she had regained consciousness, but she remained pale. An electrocardiogram (ECG) demonstrated complete AV block with a heart rate of 78 beats per minute (bpm). The ECG after admission showed a Wenckebach-type second-degree AV block. Day 2 after admission, a 12-lead ECG showed significant ST and T-wave abnormalities in the precordial leads, but the girl had no chest pain and a normal physical examination. Echocardiography demonstrated normal contractility of the systemic right ventricle. The first-degree AV block and the ST and T-wave abnormalities on the 12-lead ECG improved gradually without abnormal Q-waves. This is the first report of ccTGA in which a transient complete AV block naturally recovered after a presentation with commotio cordis.