Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Concentrations of free amino acids were measured concurrently in plasma, erythrocytes, granulocytes, and lymphocytes in umbilical cord blood, neonates, children, and adults. In each age group, the patterns of free amino acids were fairly similar in plasma and erythrocytes except for aspartic acid which was more abundant in erythrocytes. Of the amino acids in granulocytes, 71-77% was taurine; in lymphocytes taurine, aspartic acid, and glutamic acid comprised 35-44%, 18-24%, and 20-28%, respectively, of the total in all age groups. Leukocytes may contribute to the interorgan transport of amino acids to about 10% of the erythrocytes' contribution. Postnatally, the levels of glutamic acid and tyrosine in plasma; threonine plus glutamine, serine plus asparagine, and tyrosine in erythrocytes; histidine in granulocytes; and glutamic acid in lymphocytes were significantly increased (p less than 0.001); while the levels of phenylalanine and lysine in plasma; taurine in erythrocytes; valine and phenylalanine in granulocytes; and threonine plus glutamine, tyrosine, and phenylalanine in lymphocytes were significantly decreased (p less than 0.001). After the neonatal period concentrations of taurine and aspartic acid in erythrocytes, taurine and valine in granulocytes, and tyrosine and phenylalanine in lymphocytes increased gradually with age; while concentrations aspartic acid in plasma, histidine in granulocytes, and glycine in lymphocytes decreased gradually with age. The levels of glycine and valine in plasma, alanine and valine in erythrocytes, serine plus asparagine, glycine, alanine, and tyrosine in granulocytes, and aspartic acid, serine plus asparagine, and alanine in lymphocytes remained constant in all age groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Free amino acid concentrations in plasma, erythrocytes, granulocytes, and lymphocytes in umbilical cord blood, children, and adults. 673 89

Purine nucleoside phosphorylase deficiency is a rare autosomal recessive immunodeficiency disease. The characteristic features of the disease include severe T cell immune defects with recurrent infections, a failure to thrive, and progressive neurological findings. To date, 35 cases of purine nucleosidase phosphorylase deficiency have been reported worldwide. A 2-year-old female patient was hospitalized due to recurrent infections starting from 6 months and a fever that had continued for a month. The parents were first cousins. Physical examination showed a failure to thrive, herpetic lesions around the lips, painful lesions on the tongue and the buccal mucosa, lung infection, and spastic paraparesis in the lower extremities. She had motor and mental retardation. Laboratory tests revealed lymphopenia; low CD3, CD4, and CD8 counts; normal immunoglobulin levels; low uric acid; and very low purine nucleoside phosphorylase enzyme activity (1.4 nmol/h/mg; normal range, 490-1530). DNA sequencing of the purine nucleosidase phosphorylase gene revealed a missense homozygous mutation, a G to A transition at exon 4 position 64 (349G>A transition), which led to a substitution of alanine by threonine at codon 117 (Ala117Thr). Both parents were heterozygous for the mutation. This is the second purine nucleosidase phosphorylase deficient case to have been presented and carrying this mutation worldwide. Various antibiotics, antifungal drugs, and intravenous immunoglobulin were used to treat the infections during her 3 months. This form of treatment proved to be unresponsive, resulting in her subsequent death at 26 months of age.
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PMID:Purine nucleoside phosphorylase deficiency in a patient with spastic paraplegia and recurrent infections. 1764 Dec 61

T cell homeostasis is crucial for maintaining an efficient and balanced T cell immunity. The interaction between TCR and self peptide (sp) MHC ligands is known to be the key driving force in this process, and it is believed to be functionally and mechanistically different from that initiated by the antigenic TCR stimulation. Yet, very little is known about the downstream signaling events triggered by this TCR-spMHC interaction and how they differ from those triggered by antigenic TCR stimulation. In this study, we show that T cell conditional ablation of MEKK3, a Ser/Thr kinase in the MAPK cascade, causes a significant reduction in peripheral T cell numbers in the conditional knockout mice, but does not perturb thymic T cell development and maturation. Using an adoptive mixed transfer method, we show that MEKK3-deficient T cells are severely impaired in lymphopenia-induced cell proliferation and survival. Interestingly, the Ag-induced T cell proliferation proceeds normally in the absence of MEKK3. Finally, we found that the activity of ERK1/2, but not p38 MAPK, was attenuated during the lymphopenia-driven response in MEKK3-deficient T cells. Together, these data suggest that MEKK3 may play a crucial selective role for spMHC-mediated T cell homeostasis.
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PMID:MEKK3 is essential for lymphopenia-induced T cell proliferation and survival. 1926 38

We describe a novel clinical phenotype associating T- and B-cell lymphopenia, intermittent neutropenia, and atrial septal defects in 3 members of a consanguineous kindred. Their clinical histories included recurrent bacterial infections, viral infections, mucocutaneous candidiasis, cutaneous warts, and skin abscesses. Homozygosity mapping and candidate gene sequencing revealed a homozygous premature termination mutation in the gene STK4 (serine threonine kinase 4, formerly having the symbol MST1). STK4 is the human ortholog of Drosophila Hippo, the central constituent of a highly conserved pathway controlling cell growth and apoptosis. STK4-deficient lymphocytes and neutrophils exhibit enhanced loss of mitochondrial membrane potential and increased susceptibility to apoptosis. STK4 deficiency is a novel human primary immunodeficiency syndrome.
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PMID:The phenotype of human STK4 deficiency. 2250 47

Serine/threonine kinase 4 (STK4) deficiency is an autosomal recessive genetic condition that leads to primary immunodeficiency (PID) typically characterized by lymphopenia, recurrent infections and Epstein Barr Virus (EBV) induced lymphoproliferation and -lymphoma. State-of-the-art treatment regimens consist of prevention or treatment of infections, immunoglobulin substitution (IVIG) and restoration of the immune system by hematopoietic stem cell transplantation. Here, we report on two patients from two consanguineous families of Turkish (patient P1) and Moroccan (patient P2) decent, with PID due to homozygous STK4 mutations. P1 harbored a previously reported frameshift (c.1103 delT, p.M368RfsX2) and P2 a novel splice donor site mutation (P2; c.525+2 T>G). Both patients presented in childhood with recurrent infections, CD4 lymphopenia and dysregulated immunoglobulin levels. Patient P1 developed a highly malignant B cell lymphoma at the age of 10 years and a second, independent Hodgkin lymphoma 5 years later. To our knowledge she is the first STK4 deficient case reported who developed lymphoma in the absence of detectable EBV or other common viruses. Lymphoma development may be due to the lacking tumor suppressive function of STK4 or the perturbed immune surveillance due to the lack of CD4+ T cells. Our data should raise physicians' awareness of [1] lymphoma proneness of STK4 deficient patients even in the absence of EBV infection and [2] possibly underlying STK4 deficiency in pediatric patients with a history of recurrent infections, CD4 lymphopenia and lymphoma and unknown genetic make-up. Patient P2 experienced recurrent otitis in childhood, but when she presented at the age of 14, she showed clinical and immunological characteristics similar to patients suffering from Autoimmune Lymphoproliferative Syndrome (ALPS): elevated DNT cell number, non-malignant lymphadenopathy and hepatosplenomegaly, hematolytic anemia, hypergammaglobulinemia. Also patient P1 presented with ALPS-like features (lymphadenopathy, elevated DNT cell number and increased Vitamin B12 levels) and both were initially clinically diagnosed as ALPS-like. Closer examination of P2, however, revealed active EBV infection and genetic testing identified a novel STK4 mutation. None of the patients harbored typically ALPS-associated mutations of the Fas receptor mediated apoptotic pathway and Fas-mediated apoptosis was not affected. The presented case reports extend the clinical spectrum of STK4 deficiency.
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PMID:EBV Negative Lymphoma and Autoimmune Lymphoproliferative Syndrome Like Phenotype Extend the Clinical Spectrum of Primary Immunodeficiency Caused by STK4 Deficiency. 3038 45