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)

Human immunodeficiency virus (HIV) interacts with the immune system throughout the course of infection. For most of the disease process, HIV activates the immune system, and the degree of activation can be assessed by measuring serum levels of molecules such as beta 2-microglobulin and neopterin, as well as other serum and cell surface phenotype markers. The levels of some of these markers correlate with clinical progression of HIV disease, and these markers may be useful as surrogate markers for development of clinical AIDS. Because the likelihood and timing of development of clinical AIDS following seroconversion, for any particular individual, are not readily predictable, the use of nonclinical disease markers has become critically important to patient management. Surrogate markers of HIV infection are, by definition, measurable traits that correlate with disease progression. An ideal marker should identify patients at highest risk of disease progression, provide information on how long an individual has been infected, help in staging HIV disease, predict development of opportunistic infections associated with AIDS, monitor the therapeutic efficacy of immunomodulating or antiviral treatments, and the easily quantifiable, reliable, clinically available, and affordable. This review examines the current state of knowledge and the role of surrogate markers in the natural history and treatment of HIV infection. The clinical usefulness of each marker is assessed with respect to the criteria outlined for the ideal surrogate marker for HIV disease progression.
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PMID:Markers predicting progression of human immunodeficiency virus-related disease. 811 88

A tumour-associated antigen known as 90K has been found in high concentrations in the serum of patients infected with human immunodeficiency virus (HIV) even in the absence of neoplastic complications. In order to investigate the relationship between the production of 90K and soluble inflammatory mediators, we studied serum concentrations of the antigen, tumour necrosis factor-alpha (TNF-alpha), interleukin-I-alpha (IL-I-alpha), interferon-gamma (IFN-gamma), IFN-alpha, neopterin and beta 2-microglobulin (beta 2-m) in patients with non-neoplastic HIV infection at various stages of disease and in control persons. The antigen was detected in all those studied but its concentration was higher in HIV-infected patients compared with controls (P < 0.001), increasing progressively with advancing stages of disease. There was a negative correlation between concentrations of 90K and IL-I-alpha in patients in U.S.A. Centers for Disease Control groups II and III (P < 0.02) and also between that of 90K and both TNF-alpha (P < 0.01) and IL-I-alpha (P < 0.05) in control persons. The results indicate that 90K is not merely a tumour-associated antigen and that its production may be part of immune and inflammatory responses in the absence of neoplasia. The correlation between the concentrations of 90K and of some cytokines in asymptomatic patients and healthy persons suggests that 90K may be part of a network of immune and inflammatory reactants.
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PMID:Relationship between the tumour-associated antigen 90K and cytokines in the circulation of persons infected with human immunodeficiency virus. 816 31

Forty-three human immunodeficiency virus-infected patients with Pneumocystis carinii pneumonia (PCP) were enrolled in a study of adjunctive corticosteroid treatment for 10 days versus placebo, in addition to antimicrobial treatment. Levels of neopterin and beta 2-microglobulin (beta 2M) were determined in consecutive serum samples. Initiation of antimicrobial treatment resulted in significantly increased neopterin levels, whereas beta 2M levels slightly decreased from pretreatment levels. In patients treated with corticosteroid, both neopterin and beta 2M decreased, by approximately 50% and approximately 30%, respectively, and returned to baseline after discontinuation of corticosteroid treatment. Antimicrobial treatment alone did not affect either neopterin or beta 2M in healthy controls. Results indicate that treatment has a differential effect on the immune response: increased macrophage activation leading to neopterin production and decreased production of beta 2M by lymphocytes. Further, addition of corticosteroids modified and decreased this immune activation and may explain the earlier demonstrated beneficial effect of corticosteroids in PCP treatment.
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PMID:Differential effect on serum neopterin and serum beta 2-microglobulin is induced by treatment in Pneumocystis carinii pneumonia. 816 17

Cerebrospinal fluid (CSF) neopterin levels were determined by RIA in individuals with central nervous system (CNS) or human immunodeficiency virus (HIV) infections and in healthy controls. The mean CSF neopterin concentrations were 63.0 nmol/L in 15 patients with acute bacterial meningitis, 54.9 nmol/L in 15 patients with Lyme neuroborreliosis, 32.5 nmol/L in 10 patients with viral meningitis, 130.9 nmol/L in 8 patients with viral encephalitis, 13.9 nmol/L in 15 patients with asymptomatic HIV infection, 26.0 nmol/L in 11 patients with AIDS without dementia, 65.4 nmol/L in 4 patients with AIDS dementia, and 4.2 nmol/L in 24 healthy controls. Although patients with viral encephalitis had higher mean neopterin levels than any other patient category studied, the CSF neopterin concentrations cannot be used to discriminate between viral and bacterial infections. Analysis of CSF levels of neopterin may be useful as guidance in following clinical course and effect of treatment and can provide information of value in addition to CSF cell count as a measurement of CNS immune stimulation.
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PMID:Cerebrospinal fluid neopterin concentrations in central nervous system infection. 822 65

This study evaluated the effect of continued heroin use during methadone treatment on serum neopterin levels in 40 human immunodeficiency virus (HIV) type 1 seropositive (HIV+) and 70 seronegative (HIV-) intravenous drug users (IVDUs). Persistent drug use, determined by urinary evidence of opiates, was more common in HIV+ than in HIV- IVDUs (p = 0.01). Serum neopterin concentration, an indicator of increased probability of progression to AIDS, was elevated in HIV+ IVDUs, p < 0.0001 (mean 16.0 nmol/L) compared to that of HIV- IVDUs (mean 10.0 nmol/L) and in persistent IV drug users compared with abstainers, p < 0.0001. The effect of drug use and HIV status on serum neopterin was not explained by differences in methadone treatment, age, sex, or total years of i.v. drug use. Neopterin decreased in 25 IVDUs, regardless of HIV serostatus, treated with methadone for an average of 1.5 years.
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PMID:Association of immune activation with intravenous heroin use and methadone treatment in HIV-1 seropositive and seronegative subjects. 825 65

Expression of tumor necrosis factor alpha (TNF alpha), interleukin 1 beta (IL-1 beta), and interleukin 6 (IL-6) was evaluated in unstimulated peripheral blood monocytes obtained from human immunodeficiency virus-positive (HIV+) individuals using a reverse transcription-polymerase chain reaction (RT-PCR) method. In all, 40 subjects were included--13 asymptomatic, 11 with ARC, seven with AIDS, and nine HIV- controls. Of the asymptomatic individuals, 85% were positive for TNF alpha and IL-1 beta compared with only 27% of the ARC and 42% of the AIDS patients. Expression of IL-6 message was observed in lesser proportions, with no significant differences among disease states. Quantitation of IL-1 beta and TNF alpha mRNA from the positive samples fell into two categories, low responders (six of 17), with < 5,000 copies of IL-1 beta and TNF alpha mRNA, and high responders (11 of 17), with > 5,000 copies per 10 pg of total cellular RNA. There was no correlation of mRNA detection or concentration with CD4+ cell number or beta 2-microglobulin levels. However, the levels of mRNA, but not its presence alone, were positively correlated with neopterin levels. The data show differential cytokine regulation in monocytes, observed as an increase in the expression of TNF alpha and IL-1 beta compared with IL-6 in HIV+ patients. Our report also emphasizes the utility of an RT-PCR system in analyzing multiple cytokine transcript levels in small amounts of clinical materials.
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PMID:Differential expression of tumor necrosis factor alpha and interleukin 1 beta compared with interleukin 6 in monocytes from human immunodeficiency virus-positive individuals measured by polymerase chain reaction. 830 23

Expression of the gamma/delta T cell receptor (TCR) on CD3+ intraepithelial lymphocytes (IELs) was studied by two-colour immunofluorescence in duodenal tissue sections from healthy (n = 6) or infection-prone (n = 7) subjects with selective IgA deficiency (IgAD), and subjects (n = 4) with combined IgAD and IgG subclass deficiency. TCR gamma/delta+ IEL proportions in selective IgAD subjects (median 6.3%, range 1.0-41%) and in those with combined deficiency (median 4.5%, range 1.2-33%) were well within the range (0.3-38%) for histologically normal controls (n = 11), but the healthy IgAD subgroup tended to show raised TCR gamma/delta+ IEL proportions (median 13.6%) compared with the other two subgroups. Also the number of TCR gamma/delta+ IELs per intestinal length unit was relatively high (median 13.9/mm) in the healthy IgAD subjects, and significantly raised (P < 0.03) compared with controls (median 3.2/mm). Paired staining revealed that most TCR gamma/delta+ IELs in both selective IgAD (98%) and combined deficiency (99%) were CD8-, and a large fraction (median 84% and 63%, respectively) expressed the V delta 1/J delta 1-encoded epitope. The total number of CD3+ IELs (mostly CD8+) was similar to controls. IgAD subjects, and especially the healthy subgroup, had significantly increased serum concentrations of soluble CD8 (P < 0.0002), neopterin (P < 0.005), and beta 2-microglobulin (P < 0.007), which was similar to our previous observations in common variable immunodeficiency, and probably reflected stimulation of cell-mediated immunity. In addition, the increased TCR gamma/delta+ IELs might reflect a component of compensatory surface protection in the healthy IgAD subgroup.
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PMID:Duodenal intraepithelial gamma/delta T cells and soluble CD8, neopterin, and beta 2-microglobulin in serum of IgA-deficient subjects with or without IgG subclass deficiency. 840 24

Serum levels of tumour necrosis factor-alpha (TNF-alpha), neopterin and interferon-alpha (IFN-alpha) were determined by immunoradiometric assays in 60 HIV-1+ and 20 HIV-1- subjects from Ethiopia. Swedish samples were used as reference material. The Ethiopian HIV-1+ subjects were found to have significantly increased TNF-alpha and neopterin, but not IFN-alpha levels. Increased levels of TNF-alpha and neopterin were frequently found in Ethiopian asymptomatic subjects (37% and 47%), and the concentration increased in patients with AIDS (83% and 90% respectively). The levels of the two substances and the proportion of patients with higher TNF-alpha values were lower in the corresponding Swedish subjects. The proportion of sera with raised levels of IFN-alpha was very low (asymptomatic 4%, and AIDS 7%) in Ethiopian subjects. These results suggest a very early increase in the TNF-alpha production and activation of the cellular immune response, and a low level of IFN-alpha synthesis in the natural course of HIV infection in Ethiopia. The aberrations may contribute to a rapid progress of immunodeficiency and cachexia often seen in Ethiopian patients.
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PMID:Raised levels of tumour necrosis factor-alpha and neopterin, but not interferon-alpha, in serum of HIV-1-infected patients from Ethiopia. 841 84

We investigated serum levels of adenosine deaminase 2 (ADA2) and neopterin (NP) in hemophiliacs with or without infection with human immunodeficiency virus type 1 (HIV-1). The mean (+/- SD) serum ADA2 level in hemophiliacs positive for HIV-1 (45.2 +/- 17.6 U/L) and negative for HIV-1 (34.9 +/- 15.8 U/L) was significantly higher than that in healthy controls (12.0 +/- 7.0 U/L) (P < .01). The mean serum NP level was also higher in HIV-1-positive hemophiliacs (10.2 +/- 6.1 nmol/L) and HIV-1-negative hemophiliacs (7.0 +/- 2.9 nmol/L) than in the healthy controls (4.3 +/- 1.3 nmol/L). Although the HIV-1-positive hemophiliacs had higher mean ADA2 and NP levels than did hemophiliacs in the HIV-1-negative group (P < .01), the levels of most of the patients in both groups were similar. ADA2 and NP levels in serial samples from asymptomatic carriers and patients with stable AIDS showed no marked changes over a period of up to 6 years. These findings indicate that ADA2 and NP are not specific markers of HIV-1 infection in hemophiliacs. Nonspecific immunologic activation due to the repeated infusion of antihemophilic factor concentrate could be one cause for the increased serum levels of ADA2 and NP in hemophiliacs.
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PMID:Serum adenosine deaminase 2 and neopterin levels are increased in a majority of hemophiliacs irrespective of infection with human immunodeficiency virus type 1. 801 44

Serologic markers of immune activation, neopterin and beta-2-microglobulin (B2M), have been shown to predict progressive human immunodeficiency virus type 1 (HIV-1) disease based on cohort studies in adults. Both parameters appear also to be valuable in distinguishing HIV-1 infants with progressive disease from asymptomatic infants and HIV-1 seronegative infants. In a cross-sectional study we examined the utility of neopterin and B2M testing in 135 infants of an orphanage in Romania, 69 of the infants (51%) were found to be HIV-1 antibody seropositive; 95% of the 135 infants were either hepatitis B virus (HBV) antigen or antibody seropositive. In the HIV-1 seronegative infants B2M was higher in those with HBV antigenaemia. Serum neopterin and B2M concentrations were higher in HIV-1 seropositive than in seronegative infants (p = 7 x 10(-12) and 1 x 10(-6)). Children with CDC stage P2 had only slightly higher neopterin and B2M values as compared to stage P1 (P = 0.04 and 0.08). Our study indicates that measurement of neopterin and B2M is useful to monitor HIV-1 infection, particularly in areas where laboratory facilities are limited. Both parameters continue to be associated with HIV-1 infection even when there is a high background rate of other infections.
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PMID:Association between neopterin and beta-2-microglobulin levels and HIV status in Romanian orphanage children. 851 58


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