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)

Neopterin concentrations in 50 children with human immunodeficiency virus infection were correlated with disease course. The neopterin concentrations ranged from 4 to 70 nM with a mean of 34.7 +/- 25.1 (SD) nM compared with a mean of 6.1 +/- 1.6 nM in the human immunodeficiency virus-negative control group. Elevated neopterin concentrations above the upper range of the control group were detected as early as 5 months of age. Nineteen of 20 patients (95%) with neopterin concentrations above 20 nM either died or have severe clinical disease. Increasing neopterin concentrations were also associated with poor prognosis even though the first value was below 20 nM. Conversely neopterin concentrations less than 20 nM or declining concentrations were associated with a stable clinical course, except in terminal illness. With stepwise logistic regression analysis neopterin concentrations were predictive for disease progression. This predictive value was further improved by the addition of CD4 cell counts.
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PMID:Neopterin concentrations in pediatric human immunodeficiency virus infection as predictor of disease activity. 156 52

The pathogenesis of central nervous system (CNS) disease in acquired immunodeficiency syndrome (AIDS) is poorly understood but may be related to specific effects of the immune system. Cytokines such as tumor necrosis factor and interleukin-1 may have toxic effects on CNS cells and have been postulated to contribute to the pathogenesis of the neurological complications of human immunodeficiency virus (HIV) infection. To characterize viral and immunological activity in the CNS, frozen specimens taken at autopsy from the cerebral cortex and white matter of HIV-seropositive and -seronegative individuals were stained immunocytochemically for mononuclear cells, major histocompatibility complex (MHC) antigens, HIV, astrocytes, and the cytokines interleukin-1 and -6, tumor necrosis factor-alpha and -beta, and interferon gamma. Levels of soluble CD4, CD8, and interleukin-2 receptor, as well as interferon gamma, tumor necrosis factor-alpha, beta 2-microglobulin, neopterin, and interleukin-6 and -1 beta were assayed in the cerebrospinal fluid and plasma of many of these individuals during life. The HIV-seropositive group included individuals without neurological disease, those with CNS opportunistic infections, and those with HIV encephalopathy. Perivascular cells, consisting primarily of macrophages with some CD4+ and CD8+ T cells and rare B cells, were consistently MHC class II positive. MHC class II antigen was also present on microglial cells, which were frequently positive for tumor necrosis factor-alpha. HIV p24 antigen, when present, was found on macrophages and microglia. Endothelial cells were frequently positive for interleukin-1 and interferon gamma and less frequently for tumor necrosis factor and interleukin-6. There were gliosis and significant increases in MHC class II antigen, interleukin-1, and tumor necrosis factor-alpha in HIV-positive patients compared to HIV-negative brains. Cerebrospinal fluid from most of the patients tested had increased levels of tumor necrosis factor, beta 2-microglobulin, and neopterin. There was no correlation in HIV-positive individuals between levels of cytokines and the presence or absence of CNS disease. These data indicate that there is a relative state of "immune activation" in the brains of HIV-positive compared to HIV-negative individuals, and suggest a potential role for the immune system in the pathogenesis of HIV encephalopathy.
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PMID:Cytokine expression in the brain during the acquired immunodeficiency syndrome. 158 35

A cohort of 544 human immunodeficiency virus-1 (HIV-1) seropositive intravenous drug users (IVDUs) was recruited in 1988 and early 1989; data on laboratory markers, clinical symptoms, intravenous drug use, and demographics were collected. Forty-one IVDUs developed AIDS within 2 years of enrollment. Data were analyzed using methods of survival analysis. None of the individuals reported use of antiviral agents or Pneumocystis carinii prophylaxis at baseline. A very strong (p less than 0.001) dose-response relationship was identified between CD4 cell count at baseline and the subsequent development of AIDS. In multivariate analysis, both the presence of more than one clinical HIV-1-related symptom and serum neopterin greater than 12 nmol/L showed significant associations with the relative hazard (95% confidence interval) of AIDS after controlling for CD4 of 2.9 (1.6, 5.6) and 2.0 (1.0, 3.7), respectively. In these IVDUs, serum beta 2-microglobulin did not add predictive power for progression to AIDS. The effect of clinical symptoms was stronger for high CD4 cell counts, indicating the need to monitor HIV seropositive IVDUs with both laboratory studies and clinical evaluation.
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PMID:Prognostic indicators for development of AIDS among intravenous drug users. 161 68

Serum neopterin levels were analysed in 43 patients with primary hypogammaglobulinaemia (25 common variable immunodeficiency (CVI), 12 congenital hypogammaglobulinaemia (CH), six X-linked hypogammaglobulinaemia (XLH)), and in 33 healthy controls. The neopterin values were correlated to lymphocyte subset counts in peripheral blood, lymphocyte mitogen responses and clinical and histological manifestations in the study group. Serum neopterin levels were significantly elevated in all subgroups of patients and particularly in the CVI groups where the highest concentrations were found (P less than 0.001, CVI versus controls). Furthermore, in CVI and CH patients elevated neopterin levels were strongly correlated to decreased number of CD4+ lymphocytes (rs = -0.61, P less than 0.005 and rs = -0.83, P less than 0.001, respectively). In the CVI group high neopterin levels were also significantly correlated to low number of circulatory B (CD19+) lymphocytes (rs = -0.58, P less than 0.05). Both patients with moderately and those with severely depressed lymphocyte mitogen responses had significantly higher neopterin levels than those with normal responses. In addition, high neopterin levels were significantly associated with the occurrence of splenomegaly and nodular intestinal lymphoid hyperplasia. The immunological findings were consistently observed in longitudinal testing, and appeared to be characteristic for the individual patient. High serum neopterin levels are thought to be a marker for hyperactivity in monocytes/macrophages, and dysfunction of these cells may therefore be associated with fundamental immune pathology in some subgroups of primary hypogammaglobulinaemia.
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PMID:Raised serum neopterin levels in patients with primary hypogammaglobulinaemia; correlation to other immunological parameters and to clinical and histological features. 163 65

Human immunodeficiency virus (HIV) infection causes a number of clinical syndromes and many laboratory abnormalities, often heralding the development of the life-threatening opportunistic infections or malignancies that are known as the acquired immunodeficiency syndrome (AIDS). Drawing heavily on the results of prospective cohort studies, particularly those that my colleagues at the National Cancer Institute and I have conducted, this paper reviews the relationship of AIDS to clinical signs and symptoms, immunologic measures, and viral assays. The risk of AIDS in the next 3 years is at least 25 to 50% for HIV-infected subjects who have oral candidiasis, unexplained fever, unexplained weight loss, a CD4+ lymphocyte count below 200 cells/microliter, or combinations of these. Elevated serum levels of beta 2 microglobulin and neopterin also appear to be strong predictive markers of AIDS, but further work is needed in diverse HIV-infected populations, such as intravenous drug users and persons in pattern II countries, such as Haiti and central Africa. Elevated levels of interferon or HIV-p24 antigen in the serum are insensitive but highly specific AIDS markers that may have predictive value independent of CD4 lymphocyte levels. Several potentially valuable immunologic (immunoglobulin levels, tumor necrosis factor, soluble interleukin 2) and virologic (HIV viremia) assays remain to be thoroughly evaluated or technically simplified. Data from prospective cohort studies have provided clinical and laboratory markers of AIDS risk that have proved essential for therapeutic trials and other clinical decisions. As effective treatments for HIV infection and its complications begin to emerge, these marker data will also prove invaluable for mathematic modeling of the scope, course, and public health response to the epidemic.
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PMID:Prognostic markers for AIDS. 166 94

The great majority of individuals with human immunodeficiency virus type 1 (HIV-1) infection presents with no signs or symptoms, or only lymphadenopathy. To initiate prophylactic measures in time it is necessary to establish risk criteria. CD4+ cell counts are significant predictors. Supplementary methods to improve the predictive information of CD4+ cell counts are still required. In addition, CD4+ cell counting is laborious, expensive, and restricted to specialized laboratories. Thus, there is also a place for more easily performed laboratory tests with similar predictive value as CD4+ cell counts. Neopterin and beta 2-microglobulin levels proved to be significant predictors of AIDS risk in HIV-1 seropositives. The predictive value of both parameters is equal to CD4+ cell counts and both markers are significant joint predictors in addition to CD4+ cell counts. Measurement of the parameters is done in serum (neopterin and beta 2-microglobulin) or urine (neopterin) specimens which reduces the risk of HIV-1 transmission compared to handling of whole-blood samples as it is required for cell counting. Although more studies are needed, especially in developing countries and in persons receiving zidovudine, it can be recommended to use neopterin and beta 2-microglobulin as additional marker to estimate AIDS risk in HIV-1 seropositive individuals. Moreover, both markers may be useful for this purpose without CD4+ cell counts if cell counting is not available.
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PMID:Neopterin and beta 2-microglobulin as prognostic indices in human immunodeficiency virus type 1 infection. 167 20

The use of ozone therapy is reported to be effective in a variety of viral illnesses, including HIV disease. We performed a phase I study of ozone blood treatments in 10 patients in whom no significant toxicity was observed. Three patients with moderate immunodeficiency showed improvement in surrogate markers of HIV-associated immune disease. A phase II controlled and randomized double-blinded study was initiated comparing reinjection of ozone-treated blood, and reinjection of unprocessed blood for 8 weeks, followed by a 4-week observation period. Ozone had no significant effect on hematologic, biochemical or clinical toxicity when compared with placebo. CD4 cell count, interleukin-2, gamma-interferon, beta 2-microglobulin, neopterin and p24 antigen were also unaffected by both treatment arms. In conclusion, ozone therapy does not enhance parameters of immune activation nor does it diminish measureable p24 antigen in HIV-infected individuals.
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PMID:The use of ozone-treated blood in the therapy of HIV infection and immune disease: a pilot study of safety and efficacy. 134 51

We investigated whether elevated serum levels of beta 2-microglobulin and neopterin were related to the abnormal in vivo production of interferon described in patients with human immunodeficiency virus (HIV) infection, and whether these factors might add to measurements of CD4+ T cells in predicting survival and tumor regression in patients with Kaposi sarcoma associated with AIDS. beta 2-Microglobulin and neopterin levels were strongly correlated (r = 0.82), and were each significantly higher in patients with detectable serum interferon-alpha activity. Inverse correlations were observed between prognosis and levels of these serum products. Prediction by CD4+ T-cell count of tumor regression after treatment with interferon-alpha and zidovudine was improved by each of two factors: (a) the presence or absence of endogenous interferon-alpha activity, and (b) a combined variable reflecting relative levels of the interferon-inducible products, beta 2-microglobulin and neopterin. The level of beta 2-microglobulin was the single best predictor of survival. When beta 2-microglobulin was not considered, the endogenous interferon-alpha variable was the best predictor of survival, and the prediction was enhanced by addition of the combined variable, or the neopterin value alone. We conclude that serologic markers, which directly or indirectly reflect activation of the endogenous interferon system, may be valuable adjuncts to CD4+ T-cell counts in assessing prognosis and selecting and evaluating treatments for patients with Kaposi sarcoma and AIDS.
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PMID:Relationship and prognostic value of endogenous interferon-alpha, beta 2-microglobulin, and neopterin serum levels in patients with Kaposi sarcoma and AIDS. 189 8

We measured the levels of interferon-gamma (IFN-gamma) and neopterin in the serum and cerebrospinal fluid of 121 human immunodeficiency virus-seropositive (HIV+) and 62-seronegative (HIV-) individuals evaluated for neurologic disease. CSF levels of IFN-gamma and serum and CSF levels of neopterin were higher in HIV+ than in HIV- individuals. Patients with HIV- related meningitis and with opportunistic CNS infections had higher serum neopterin levels than HIV+ asymptomatic individuals. CSF levels of IFN-gamma were slightly higher in CSF of HIV+ individuals in all groups (0.31 +/- 0.03 U/ml) than in HIV- individuals (0.12 +/- 0.03). CSF levels of neopterin were similar in HIV+ asymptomatic individuals (6.9 +/- 0.7 nmol/l) and HIV- individuals (5.9 +/- 1.1), but were elevated in those HIV-infected individuals with neurologic disease, particularly patients with HIV-associated meningitis (72.1 +/- 13.3 nmol/l), opportunistic CNS infections (36 +/- 9.1), and inflammatory demyelinating polyneuropathies (32.4 +/- 17.2). Levels of neopterin correlated positively with levels of soluble interleukin 2 receptor and soluble CD8, 2 additional indicators of immune activation. In the absence of neurologic disease, levels of IFN-gamma and neopterin in both serum and CSF were stable for up to 4 years after seroconversion. These data suggest that increased CSF neopterin is associated with HIV-associated neurologic disease.
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PMID:Neopterin and interferon-gamma in serum and cerebrospinal fluid of patients with HIV-associated neurologic disease. 189 75

Antibodies against human immunodeficiency virus, other infectious agents and neopterin levels were determined in 253 patients in a rural area of North-West Tanzania. Seroprevalence for HIV was 3.2%. In one case serology was positive for HIV-1 and HIV-2 antibodies and questions whether there was a real double infection or a cross reaction not only concerning core region proteins but also transmembrane protein. The specificity in the diagnosis of HIV-infection is markedly increased with newer serological methods using recombinant peptides but did not improve sensitivity on African sera. Neopterin was determined as a sensitive indirect marker for the activation of T-cells and is therefore correlated with the susceptibility of HIV infection and with progression of disease. High seroprevalence rates for various infectious agents were determined and may explain the high rate of elevated neopterin levels in 80% of the Africans. Neopterin levels were even higher in HIV patients. Viral p24 antigen was found only in two persons, one of whom had no antibodies detectable.
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PMID:Evaluation on HIV serology and immune-stimulation on patients in Tanzania. 190 99


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