Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A chronic, debilitating syndrome related to graft-versus-host disease (GVHD) has been recognized in long-term survivors following allogeneic bone marrow transplantation. In six of 20 marrow graft recipients who survived for more than one year after receiving a transplant, this complication developed; they were studied to better define the syndrome. There was no association between the sex of either donor or recipient, HLA type, blood group, conditioning regimen or marrow cell dose and subsequent development of chronic GVHD. All six patients had mild to moderate manifestations of acute GVHD following prompt engraftment. Chronic GVHD was characterized in each patient by progression to scleroderma-like skin involvement with hyperkeratosis, reticular hyperpigmentation, atrophy with ulceration and fibrosis with limitation of joint movement. A sicca syndrome was prominent in five patients. Four patients had idiopathic interstitial pneumonitis. Infectious complications were frequent, and DNA viral infections were prominent. Autoimmune hemolytic anemia was present in three patients, and one patient had antinuclear antibody (ANA). A spectrum of immune abnormalities was observed including hypergammaglobulinemia, immunoglobulin M (IgM) paraprotein, elevated circulating immune complexes, plasma cell hyperplasia, lymphocytotoxic antibodies and autoantibodies to autologous or donor lymphocytes. Despite clinical similarity to collagen vascular diseases, none of these patients had anti-DNA antibodies or antibodies to smooth muscle, thyroid or extractable nuclear antigens. In one patient, a skin graft from the marrow donor remained healthy despite progressive involvement in recipient skin, whereas unrelated skin grafts were rejected. Immunosuppressive therapy and plasmapheresis have not been effective. Four patients have died (median survival 458 days from transplantation). Chronic GVHD appears to be a syndrome of disordered immune regulation features of immunodeficiency and autoimmunity.
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PMID:Chronic graft versus host disease: a syndrome of disordered immunity. 3 1

A 13-month-old boy had a "late-onset" form of combined immunodeficiency and a fulminant Pneumocystis carinii pneumonia of one month's duration. There was no evidence of cutaneous-delayed hypersensitivity responses to diphtheria-tetanus toxoids, Candida albicans, or streptokinase-streptodornase, or of lymphocyte DNA synthesis after in vitro stimulation with the mitogens phytohemagglutinin and concanavalin A, and only 2% to 4% of peripheral blood E-rosetted T lymphocytes. The serum IgM level was normal (62 mg/dL), whereas the other immunoglobulins were markedly reduced. Despite an increased number of Ig-bearing lymphocytes, in vitro Ig secretion after pokeweed mitogen stimulation was substantially reduced. The thymus gland was dysplastic with no Hassalls' corpuscles or thymocytes, and other lymphoid organs showed depletion of T-dependent areas to a greater extent than the B-dependent areas.
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PMID:Diagnostic dilemma of a 13-month-old boy with 'late-onset' combined immunodeficiency. 8 98

Deoxyadenosine and deoxyguanosine are toxic to human lymphoid cells in culture and have been implicated in the pathogenesis of the immunodeficiency states associated with adenosine deaminase and purine nucleoside phosphorylase deficiency, respectively. We have studied the relative incorporation of several labeled nucleosides into DNA and into nucleotide pools to further elucidate the mechanism of deoxyribonucleoside toxicity. In the presence of an inhibitor of adenosine deaminase [erythro-9-(2-hydroxy-3-nonyl)adenine [EHNA], 5 muM], deoxyadenosine (1-50 muM) progressively decreased the incorporation of thymidine, uridine, and deoxyuridine into DNA, but did not affect uridine incorporation into RNA. This decrease in DNA synthesis was associated with increasing dATP and decreasing dCTP pools. Likewise, incubation of cells with deoxyguanosine caused an elevation of dGTP, depletion of dCTP, and inhibition of DNA synthesis. To test the hypothesis that dATP and dGTP accumulation inhibit DNA synthesis by inhibiting the enzyme ribonucleotide reductase, simultaneous rates of incorporation of [(3)H]uridine and [(14)C]thymidine into DNA were measured in the presence of deoxyadenosine plus EHNA or deoxyguanosine, and in the presence of hydroxyurea, a known inhibitor of ribonucleotide reductase. Hydroxyurea (100 muM) and deoxyguanosine (10 muM) decreased the incorporation of [(3)H]uridine but not of [(14)C]thymidine into DNA; both compounds also substantially increased [(3)H]cytidine incorporation into the ribonucleotide pool while reducing incorporation into the deoxyribonucleotide pool. In contrast, deoxyadenosine plus EHNA did not show this differential inhibition of [(3)H]uridine incorporation into DNA, and the alteration in [(3)H]cytidine incorporation into nucleotide pools was less impressive. These data show an association between accumulation of dATP or dGTP and a primary inhibition of DNA synthesis, and they provide support for ribonucleotide reductase inhibition as the mechanism responsible for deoxyguanosine toxicity. Deoxyadenosine toxicity, however, appears to result from another, or perhaps a combination of, molecular event(s).
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PMID:Purinogenic immunodeficiency diseases. Differential effects of deoxyadenosine and deoxyguanosine on DNA synthesis in human T lymphoblasts. 11 1

We have studied three patients with ataxia-telangiectasia (AT) and found two of them to have a normal mixed leucocyte culture stimulating and responding ability. However, all three patients and one parent had defective cell-mediated lympholysis (CML), even in the face of a potent proliferative response to allogeneic leucocytes. None of these patients showed significant proliferative responses to common microbial antigens (tetanus toxoid, Candida albicans, purified protein derivative (PPD), diphtheria toxoid, influenza). Our studies indicate tha the T cell defect in AT preferentially affects certain T cell functions associated with antigen recognition and the generation of allogeneic CML, while sparing the allogeneic proliferative response. The selective deficiency of specific lymphocyte functions in a thymic immunodeficiency with a known defect in DNA repair is consistent with the concept that DNA modulating enzymes are important for T cell function.
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PMID:Selective defects in T cell function in ataxia-telangiectasia. 15 50

Blood lymphocytes from nineteen patients with Hodgkin's disease were tested in vitro before and after treatment. The patients were retested in complete and unmaintained remission at least 15 months after termination of radiotherapy. All patients except two had been treated with total nodal irradiation. The lymphocyte-DNA synthesis induced by concanavalin A (Con A) and PPD was poor and the spontaneous DNA synthesis was increased in untreated patients. Most patients had a T lymphocytopenia before treatment. After irradiation the total lymphocyte counts were reduced drastically. The number of T lymphocytes was particularly low, though the number of B lymphocytes decreased as well. However, the lymphocyte response to Con A and PPD remained low and unchanged. The results may suggest a persisting immunodeficiency in Hodgkin's disease as reflected by the lymphocyte response to Con A and PPD.
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PMID:Persisting lymphocyte deficiences during remission in Hodgkin's disease. 30 64

We studied the immunocompetence of 6 healthy twins, whose monozygotic or dizygotic same-sexed twin partner had died from Hodgkin's disease. Lymphocyte DNA synthesis induced by concanavalin A was markedly reduced at 3 different concentrations in all twins compared to an age-matched group of healthy controls. The lymphocyte response to pokeweed mitogen and to phytohaemagglutinin was also impaired. PPD induced lymphocyte DNA synthesis was low in 3 twins and correlated well with their delayed skin hypersensitivity to the antigen. One twin was completely anergic to 3 different skin antigens. The mean total blood lymphocyte count did not differ from that of controls. There was no change in T or B-lymphocyte subpopulations. The presence of a functional lymphocyte deficiency in all twins strongly suggests that the immunodeficiency in Hodgkin's disease is partly caused by genetic and/or environmental factors.
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PMID:Immunological defects in healthy twin siblings to patients with Hodgkin's disease. 56 30

27 consanguineous and non-consanguineous relatives to 12 patients with Hodgkin's disease (HD) have been studied. The lymphocyte DNA synthesis induced by concanavalin (ConA) was depressed in 6 patients. 7 out of 15 tested relatives (3 first degree relatives and 4 spouses) showed a profound impairment in lymphocyte response to ConA stimulation. None out of 12 relatives to ConA normal patients was defect in this respect. In relatives to ConA hyporesponsive patients there was a small but statistically significant decrease in lymphocyte response to pokeweed mitogen (PWM) and PPD in vitro. No differences in lymphocyte subpopulations were seen. The findings strongly support an exogenous factory (probably a virus) causing the depressed mitogen response in relatives to immunodeficient patients with HD. A possible linkage between the immunodeficiency and the pathogenesis of HD is discussed.
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PMID:Immunological family studies in Hodgkin's disease. Is the immunodeficiency horizontally transmitted? 65 9

Transcobalamin II (TC II) is a serum protein responsible for transporting vitamin B12 to the cells. A previous observation of a child with congenital TC II deficiency and agammaglobulinemia suggested that this protein plays an important role in the immune response. Accordingly, TC II levels ere determined in 32 patients with autoimmune disease (AID) (i.e. 26 with lupus erythematosus, 4 with dermatomyositis, and 2 with autoimmune hemolytic anemia) and in 40 patients with acquired immunodeficiency due to chemotherapy. It was found that elevated TC II levels corresponded to active phases of AID. Changes in TC II levels correlated better with the clinical course of AID than complement, antinuclear antibody or native DNA binding capacity. This suggests that TC II could be a valuable parameter in following up activity of AID.
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PMID:[Increase of unsaturated transcobalamine II in autoimmune diseases; effect of immunosuppressive therapy (proceedings)]. 69 99

Twenty-seven patients (18 females and 9 males) with myasthenia gravis were HLA-A, -B, -C, and -D typed, and the results were analyzed with relation to evidence of immunodeficiency, thymic disease, and associated autoimmune processes. An association of A1, B8, and DRW3 appeared to identify a group of 8 females with higher mean anti-DNA, lower mean C4, and lower mean E. coli antibody titer than other females in whom CW4 (with or without BW35) was common (6 of the remaining 10 females were in this category). Antiacetylcholine receptor (anti-AChR) autoantibody and reduced serum IgM and isohemagglutinin titers were not clearly related to particular HLA specificities. These results suggest that HLA-A1, -B8, -DRW3, and -CW4 may be related to associated phenomena rather than playing a major role in the development of anti-AChR and myasthenia gravis.
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PMID:HLA, anti-DNA, and complement in myasthenia gravis. 75 69

The association of a human genetic deficiency of adenosine deaminase activity with combined immunodeficiency prompted a study of the effects of adenosine and of inhibition of adenosine deaminase activity on human lymphocyte transformation and a detailed study of adenosine metabolism throughout phytohemagglutinin-induced blastogenesis. The adenosine deaminase inhibitor, coformycin, at a concentration that inhibited adenosine deaminase activity more than 95%, or 50 muM adenosine, did not prevent blastogenesis by criteria of morphology or thymidine incorporation into acid-precipitable material. The combination of coformycin and adenosine, however, substantially reduced both the viable cell count and the incorporation of thymidine into DNA in phytohemagglutinin-stimulated lymphocytes. Incubation of lymphocytes with phytohemagglutinin for 72 h produced a 12-fold increase in the rate of deamination and a 6-fold increase in phosphorylation of adenosine by intact lymphocytes. There was no change in the apparent affinity for adenosine with either deamination or phosphorylation. The increased rates of metabolism, apparent as early as 3 h after addition of mitogen, may be due to increased entry of the nucleoside into stimulated lymphocytes. Increased adenosine metabolism was not due to changes in total enzyme activity; after 72 h in culture, the ratios of specific activities in extracts of stimulated to unstimulated lymphocytes were essentially unchanged for adenosine kinase, 0.92, and decreased for adenosine deaminase, 0.44. As much as 38% of the initial lymphocyte adenosine deaminase activity accumulated extracellularly after a 72-h culture with phytohemagglutinin. In phytohemagglutinin-stimulated lymphocytes, the principal route of adenosine metabolism was phosphorylation at less than 5 muM adenosine, and deamination at concentrations greater than 5 muM. In unstimulated lymphocytes, deamination was the principal route of adenosine metabolism over the range of adenosine concentrations studied (0.5-250 muM). These studies demonstrate the dependence of both the unstimulated and stimulated lymphocyte on adenosine and may account for the observed sensitivity of mitogen-stimulated lymphocytes to the toxic effects of exogenously supplied adenosine in the presence of the adenosine deaminase inhibitor coformycin. A single case of immunodeficiency disease has been reported in association with purine nucleoside phosphorylase deficiency. The catabolism of guanosine was also found to be enhanced in stimulated normal lymphocytes; phosphorolysis of guanosine to guanine by intact lymphocytes increased six fold after 72-h culture with phytohemagglutinin. The specific activity of purine nucleoside phosphorylase in extracts, with guanosine as substrate, was essentially the same in stimulated and unstimulated lymphocytes after 72 h of culture.
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PMID:Adenosine metabolism in phytohemagglutinin-stimulated human lymphocytes. 95 93


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