CD31 + CD45RA + RO -lymphocytes contain high numbers of T cell receptor circle (TREC)-bearing T cells; however, the correlation between CD31 + CD4 + lymphocytes and TREC during aging and under lymphopenic conditions has not yet been sufficiently investigated. We analyzed TREC, telomere length and telomerase activity within sorted CD31 + and CD31 -CD4 + lymphocytes in healthy individuals from birth to old age. Sorted CD31 + CD45RA + RO -naive CD4 + lymphocytes contained high TREC numbers, whereas CD31 + CD45RA -RO + cells (comprising 5% of CD4 + cells during aging) did not contain TREC. CD31 + overall CD4 + cells remained TREC rich despite an age-related tenfold reduction from neonatal (100 : 1000) to old age (10 : 1000). Besides a high TREC content, CD31 + CD45RA + RO -CD4 + cells exhibited significantly longer telomeres and higher telomerase activity than CD31 -CD45RA + RO -CD4 + cells, suggesting that CD31 + CD45RA + RO -CD4 + cells represent a distinct population of naive T cells with particularly low replicative history. To analyze the value of CD31 in lymphopenic conditions, we investigated six children after allogeneic hematopoietic stem cell transplantation (HSCT). Reemerging overall CD4 + as well as naive CD45RA + RO -CD4 + cells predominantly expressed CD31 and correlated well with the recurrence of TREC 5-12 months after HSCT. Irrespective of limitations in the elderly, CD31 is an appropriate marker to monitor TREC-rich lymphocytes essentially in lymphopenic children after HSCT.
Summaryobjective Hypoxia predicts mortality in children with acute lower respiratory infections (ALRIs). We investigated the prevalence and predictive value of hypoxia in ALRI and other acute infectious diseases.methods We studied the spectrum of hypoxaemia in 4047 children admitted to a tertiary hospital in The Gambia. Oxygen saturation was measured shortly after admission. Severe hypoxaemia was defined as an oxygen saturation below 90%.results 5.8% of all admissions had severe hypoxaemia. Prevalence of hypoxaemia varied between disease groups: it was 11.7% in ALRI cases, 16.5% in neonates; 2.9% in malaria cases overall but 6.5% in cerebral malaria patients; and 2.7% in children with meningitis. Hypoxaemia predicted a poor outcome; the odds ratio for death among paediatric admissions overall was 7.
X-linked osteopetrosis, anhydrotic ectodermal dysplasia, and immunodeficiency (XL-O-EDA-ID) is a disorder that is caused by hypomorphic mutations in the nuclear factor kappaB essential modulator (NEMO). These mutations lead to an impaired NF-kappaB activation. In vitro analyses and studies in animal models show that inhibition of NF-kappaB leads to a decrease of cytokine production and T-cell proliferation. Patients classically display poor or delayed inflammatory response to infections. We describe a boy with XL-O-EDA-ID, 1167-1168insC NEMO mutation, and recurrent infections. In early infancy, he experienced hemophagocytosis with transient deficiency of natural killer activity. Increased immunoglobulin M levels in blood resulted from a monoclonal immunoglobulin M gammopathy. Blood T-cell numbers were constantly increased, most probably resulting from a peripheral T-cell expansion. Our observations suggest that patients with hypomorphic NEMO mutations and repeated infections may experience inflammatory dysregulation.
SummaryA subgroup of patients with 22q11·2 microdeletion and partial DiGeorge syndrome (pDGS) appears to be susceptible to non-cardiac mortality (NCM) despite sufficient overall CD4 + T cells. To detect these patients, 20 newborns with 22q11·2 microdeletion and congenital heart disease were followed prospectively for 6 years. + T cell numbers were observed in 65%/75%, respectively, of patients in period A (< 1 year) declining to 22%/50%, respectively, of patients in period B (> 1/< 7 years). The percentage of patients with low CTLs (< P10) remained robust until school age (period A: 60%; period B: 50%). Low numbers of CTLs were associated with abnormally low naive CD45RA+ RO -CD4 + T cells. A high-risk (HR) group (n = 11) and a standardrisk (SR) (n = 9) group were identified. HR patients were characterized by low numbers of both naive CD4+ and CTLs and were prone to lethal infectious and lymphoproliferative complications (NCM: four of 11; cardiac mortality: one of 11) while SR patients were not (NCM: none of nine; cardiac mortality: two of nine). Naive CD31 + CD45RA + RO -CD4 + , naive CD45RA + RO -CD4 + T cells as well as TRECs/10 6 mononuclear cells were abnormally low in HR and normal in SR patients. Longitudinal monitoring of naive CD4+ and cytotoxic T cells may help to discriminate pDGS patients at increased risk for NCM.
The castor bean tick Ixodes ricinus has been found to be the main vector for Lyme borreliosis spirochetes and Anaplasma phagocytophilum in Central Europe. 1646 I. ricinus ticks from Hanover, a city located in Northern Germany, were examined for infection with A. phagocytophilum and coinfection with Borrelia burgdorferi sensu lato (sl) to obtain so far missing prevalence data for this region. The total A. phagocytophilum infection rate was 3.2% (52/1646 ticks), divided into 4.1% (32/777) adults and 2.3% (20/869) nymphs. Coinfections with B. burgdorferi sl were found in 0.9% of all tick stages. The detected genospecies were B. afzelii, B. garinii, B. burgdorferi sensu stricto (ss), and B. garinii, which was the most frequent species in coinfected ticks.
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