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)

Apart from lymphocytes, mononuclear phagocytes play an essential role as target cells for human immunodeficiency virus (HIV). Circulating blood monocytes (MOs) and tissue macrophages (M phi) may harbor and distribute the virus throughout the body. In addition, proinflammatory monokines [interleukin-1 (IL-1), IL-6, IL-8, tumor necrosis factor-alpha (TNF-alpha)] may contribute to the pathogenesis of HIV-mediated diseases. We have established a culture system on hydrophobic Teflon membranes for blood-borne MOs/M phi. Both freshly isolated MOs as well as MO-derived M phi could be infected with a monocytotropic HIV-1 isolate (HIV-1D117III) derived from a perinatally infected child. The virus production monitored by assay for viral antigen in cell-free supernatant is continuous for several weeks. We analyzed the stimulus response and the secretory repertoire of MOs/M phi early after infection with HIV as well as in long-term cultured, virus-replicating cells. Infected MOs/M phi respond to interferon-gamma more effectively than control cells as estimated from the release of neopterin. The response to lipopolysaccharide was regulated differently: whereas the proinflammatory cytokines IL-1, IL-6, IL-8 and TNF-alpha were up-regulated and even constitutively secreted upon infection, the production of the hematopoietin macrophage-colony-stimulating factor decreased. High levels of TNF-alpha and IL-1 might augment the infectibility of M phi by HIV in an autocrine manner. Our results may provide some explanation for the immunologic dysfunction, the hematopoietic failure and the chronic inflammatory disease occurring in HIV-infected patients.
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PMID:Secretory repertoire of HIV-infected human monocytes/macrophages. 190 44

Reduced tryptophan and increased kynurenine concentrations have been reported in patients with human immunodeficiency virus type 1 (HIV-1) infection. From in vitro data it appears that activated indoleamine 2,3-dioxygenase (IDO) is involved in this metabolic change. IDO is inducible by interferon-(IFN)-gamma. We compared serum concentrations of IFN-gamma and neopterin (the biosynthesis of which is also inducible by IFN-gamma) with serum, tryptophan and kynurenine of 42 patients with HIV-1 infection. IFN-gamma, neopterin and kynurenine levels were significantly increased compared to HIV-1 seronegative controls whereas tryptophan was significantly decreased. Various significant correlations were found between tryptophan, kynurenine, IFN-gamma and neopterin concentrations. Highest degree of correlation was found between neopterin, IFN-gamma and the kynurenine per tryptophan quotient which is the ratio between the product and the substrate concentration of IDO. The data indicate that decreased tryptophan in HIV-1 seropositives may result from chronic immune activation and can be referred to increased activation of IDO.
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PMID:Increased endogenous interferon-gamma and neopterin correlate with increased degradation of tryptophan in human immunodeficiency virus type 1 infection. 190 3

The present study was undertaken to discuss whether measurement of neopterin (NP) released into blood from monocytes/macrophage following activation of lymphocytes were useful tool to predict development of AIDS after HIV-1 infection. The subjects used for this study were eighty one cases of hemophilia, of whom 47 cases were HIV-1 antibody tested positive. Serum NP concentration (15.0 +/- 13.8 nmol/l) in anti-HIV-1 antibody-positive group was higher than in-negative group (5.7 +/- 3.3 nmol/l) (p less than 0.05), in which there was no case whose serum NP level amounted to more than 20 nmol/l. In anti-HIV-1 antibody-positive group, in which CD4/CD8 lymphocyte ratio was less than 0.4, serum NP level was significantly higher than in the group whose lymphocyte ratio was more than 0.5 (p less than 0.05). This result represents that there is a reverse correlation of NP concentration with the developing level of immunodeficiency. Furthermore, in eight cases who developed AIDS, serum NP levels turned to increase from several months or earlier until in all cases the levels were more than 30 nmol/l. In three cases of five who were dead, serum NP concentration had decreased to death since several months through one year. These findings reveal that measurement of serum NP concentration is correlated with clinical outcome after HIV-1 infection and it is useful as the marker for prediction of AIDS development. Also these findings represent that a parallel application of serum NP assay to CD4 lymphocyte counting, detection of anti-HIV-1 antibody, IgA, beta 2-microglobulin assays can predict the outcome of the HIV-1 infection more precisely.
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PMID:[Study on serum neopterin concentration in hemophiliacs with anti-human immunodeficiency-virus type I antibody]. 192 Aug 67

We evaluated three cellular and five serologic markers that are affected by infection with the human immunodeficiency virus type 1 (HIV-1) for their ability to predict the progression to clinical acquired immunodeficiency syndrome (AIDS). The cellular markers were the number of CD4+ T cells, the number of CD8+ T cells, and the ratio of CD4+ T cells to CD8+ T cells. The serologic markers were the serum levels of neopterin (a product of stimulated macrophages), beta 2-microglobulin, soluble interleukin-2 receptors, IgA, and HIV p24 antigen. We evaluated the usefulness of these measures as markers of the progression to AIDS prospectively, over four years, in a cohort of 395 HIV-seropositive homosexual men who were initially free of AIDS. CD4+ T cells (expressed as an absolute number, a percentage of lymphocytes, or a ratio of CD4+ to CD8+ T cells) were the best single predictor of the progression to AIDS, but the serum neopterin and beta 2-microglobulin levels each had nearly as much predictive power. The neopterin level appeared to be a slightly better predictor than the beta 2-microglobulin level. The levels of IgA, interleukin-2 receptors, and p24 antigen had less predictive value. A stepwise multivariate analysis indicated that the best predictors, in descending order, were CD4+ T cells (the percentage of lymphocytes or the CD4+: CD8+ ratio), the serum level of neopterin or beta 2-microglobulin, the level of IgA, that of interleukin-2 receptors, and that of p24 antigen. The last three markers had little additional predictive power beyond that of the first two. We conclude that of the eight markers studied, progression to AIDS was predicted most accurately by the level of CD4+ T cells in combination with the serum level of either neopterin or beta 2-microglobulin. At least one of these two serum markers, which reflect immune activation, should be used along with measurement of CD4+ T cells in disease-classification schemes and in the evaluation of responses to therapy.
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PMID:The prognostic value of cellular and serologic markers in infection with human immunodeficiency virus type 1. 197 15

Serum from 36 intravenous drug abusers without acquired immunodeficiency syndrome (AIDS) or AIDS-related complex were tested for concentrations of neopterin and beta 2-microglobulin. The seroprevalence of human immunodeficiency virus (HIV) antibody in this group was 50%. Previous studies of this group showed that the HIV antibody positive patients had significant increases in HLA-DR expression on peripheral blood lymphocytes and increases in serum soluble CD8 antigen. Both neopterin and beta 2-microglobulin concentrations were significantly higher in the HIV antibody seropositive patients compared to the seronegative patients (p = 0.001 and p = 0.005, respectively). A highly significant positive correlation between neopterin and beta 2-microglobulin was found for the seropositive patients (r = 0.8879, p less than 0.0001) as well as for the entire group (r = 0.6054, p = 0.0002). Significant positive correlations were also found between neopterin or beta 2-microglobulin and the percent DR + T cells and CD8 antigen levels, although these correlations were not as significant as that observed between neopterin and beta 2-microglobulin. No relationships were found between neopterin or beta 2-microglobulin and total CD4 cell concentrations or CD4/CD8 ratios. These data demonstrate the significant interrelationships between various immune activation markers in a population at risk for developing AIDS.
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PMID:Close relationships between neopterin and beta-2-microglobulin levels in intravenous drug abusers. 197 99

In vitro studies implicate classical and alternative complement pathway activation in the pathogenesis of human immunodeficiency virus (HIV) infection. To ascertain their importance in vivo, activation fragments of the classical (C4d), alternative (Ba), and common (C3d) pathways were measured and fragment to parent molecule ratios derived in 74 HIV-infected individuals and related to circulating immune complex (CIC) levels, Centers for Disease Control (CDC) stage, and beta 2-microglobulin, neopterin, and CD4-positive (CD4+) lymphocyte levels. All fragments and ratios were significantly higher in patients (P less than .01) than controls. C4 conversion indices (C4d and C4d to C4) increased linearly with increasing CDC stage (P less than .001), while CD4+ lymphocytes decreased linearly (P less than .001). C4d, C3d, C4d to C4, and C3d to C3 correlated with increasing CIC and beta 2-microglobulin, and C4d and C4d to C4 correlated with decreasing CD4+ lymphocytes (P less than .05). The relationship of classical complement pathway activation to disease progression and CD4+ lymphocytes suggests its involvement in the pathogenesis of HIV infection.
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PMID:Activation of the complement system in human immunodeficiency virus infection: relevance of the classical pathway to pathogenesis and disease severity. 197 7

In a prospective study, 29 patients were observed over a period of 42 weeks for signs of oral candidosis (OC), immunological parameters and other typical AIDS-related events. Before the study started, no OC was observed in any of the patients. During the observation period, OC was diagnosed in 12 of the 29 patients (41%). 5 of these 12 patients (42%) developed full-blown AIDS during the 42 weeks. In contrast, a progression to AIDS was observed in only 1 of the 17 patients (5.9%) without OC. The laboratory findings for patients with and without OC showed statistically significant differences for neopterin (23.6 against 14.4 nmol l-1), CD4 counts (417 against 763/mm3) and CD4/CD8 ratios (0.45 against 0.85). Based on these results, it seems justifiable to consider prophylactic measures such as pentamidine inhalation and/or treatment with zidovudine in HIV-infected patients with immunodeficiency and occurrence of OC.
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PMID:Oral candidosis in HIV-infected patients. Prognostic value and correlation with immunological parameters. 198 18

The possible existence of human immunodeficiency virus type 1 (HIV-1) infection in asymptomatic seronegative at-risk individuals was investigated in a prospective study of 55 seronegative high-risk individuals (42 homosexual men and 13 heterosexual individuals) and 32 seronegative hemophiliacs treated with factor VIII or IX concentrates before viral inactivation by heat treatment and systematic screening of blood donations. Tests used include the polymerase chain reaction assay with three primer pairs (one in the gag region and two in the pol region) and tests for serum p24 antigen, anti-nef serology (Western blot), and five biologic markers frequently altered by HIV infection (CD4 lymphocyte count, serum beta 2-microglobulin and neopterin concentration, and serum IgG and IgA concentration). Although 91 of 92 HIV-1-seropositive persons were positive in testing with at least one primer pair, no positive result was observed in seronegative at-risk individuals or in 117 seronegative low-risk controls. No nef antibody was found in seronegative at-risk individuals or seronegative controls, but 44 (47%) of 92 HIV-1-seropositive persons had nef antibodies. These findings do not support the existence of frequent HIV-1 infection in seronegative at-risk individuals.
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PMID:No evidence of frequent human immunodeficiency virus type 1 infection in seronegative at-risk individuals. 200 21

Increased concentrations of neopterin, a marker for cell-mediated immune activation, and decreased numbers of CD4+ T cells, are predictors for progression of disease after infection with human immunodeficiency virus type 1. Previous studies have demonstrated different rates of onset of full-blown acquired immunodeficiency syndrome (AIDS) for groups of patients, defined by laboratory marker values, who were initially symptom-free. By re-analysis of one such study, we demonstrate how for an individual patient, the individual marker values, together with a prior risk estimate, can be converted into current or accumulated post-test probability of onset of AIDS at a certain time. We used a statistical technique suggested by Albert et al. (Clin Chem 1984;30:69-76), which allows incorporation of fixed and time-dependent covariates. Besides allowing individual projections, the method shows that the predictive abilities of CD4+ T cell numbers and of neopterin concentrations do not vary greatly with regard to time of observation; both laboratory markers independently modulate the underlying prior probability of AIDS onset, which is significantly increased with the passage of time.
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PMID:Individual probability for onset of full-blown disease in patients infected with human immunodeficiency virus type 1. 200 42

Anaemia is a frequent complication in patients with human immunodeficiency virus type 1 (HIV-1) infection. We tested 14 children with severe haemophilia (9 HIV-1 antibody seropositive CDC stage IIA, 5 seronegative) for haemoglobin and urinary neopterin concentrations and found a negative correlation between neopterin and haemoglobin (rs = -0.745, p = 0.007; Spearman's rank correlation). This finding suggests that chronic immune activation, possibly along with the release of specific cytokines such as interferon gamma and tumor necrosis factor alpha may be involved in the pathogenesis of anaemia.
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PMID:Low haemoglobin in haemophilia children is associated with chronic immune activation. 202 56


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