Biomedical subjects

T Denny

Publications and source records attributed to T Denny.

At least 19 recordsLinked to original sources

PubMed2001

Decreased interferon-alpha production in HIV-infected patients correlates with numerical and functional deficiencies in circulating type 2 dendritic cell precursors.

Peripheral blood mononuclear cells from patients with human immunodeficiency virus (HIV) infection exhibit a progressively marked decrease in the production of virus-induced interferon (IFN)-alpha, a finding that correlates with and is highly predictive of disease progression and opportunistic infections. The major IFN-alpha producing population has recently been defined as the precursor to type 2 dendritic cells (pDC2) or plasmacytoid DC (pDC). Using four-color flow cytometry, we have enumerated the pDC2 vs non-IFN-alpha producing myeloid DC1 in peripheral blood from HIV-infected patients and healthy controls and related these values to CD4 cell numbers, viral load, and functional activity. The patients had reductions in the numbers of both pDC2 (lin-/HLA-DR+/CD123(bright)) and DC1 (lin1-/HLA-DR+/CD123(dim)/CD11c+), both at an absolute level and as a percentage of cells. The decreases were most evident in patients with decreased CD4 levels. Viral load correlated with the functional frequency of the IFN producing cells but not with absolute pDC2 levels. Using intracellular flow cytometric analysis for IFN-alpha, the patients were demonstrated to have fewer pDC2, as well as a lower percentage of responding cells among those remaining. We conclude that deficient production of IFN-alpha by pDC2 from HIV-infected patients results from both selective loss of these cells and their qualitative dysfunction. Given the central role of DC, and in particular, DC2, in linking innate and adaptive immune responses, these qualitative and quantitative changes in pDC2 are likely to be key contributors to HIV pathogenesis.

CD4 Lymphocyte Count↗

PubMed2001

Increased incidence of sepsis and altered monocyte functions in severely injured type A- glucose-6-phosphate dehydrogenase-deficient African American trauma patients.

OBJECTIVE: To determine whether trauma patients with the common, type A- glucose-6-phosphate dehydrogenase (G6PD) deficiency have an aggravated inflammatory response, increased incidence of septic complications, and/or more profound alterations in leukocyte functions compared with nondeficient trauma patients. SETTINGS: Intensive and surgical care units of a trauma center and flow cytometry and experimental laboratories at a teaching university hospital. DESIGN: Prospective cohort clinical study with measurements on days 2 and 5 postinjury. Monocyte and neutrophil oxidant content, apoptosis, and CD11b expression and plasma cytokine levels were compared between G6PD-deficient and nondeficient patients. PATIENTS: A total of 467 male African American trauma patients were screened for the deficiency. Forty-four type A-202/376 G6PD-deficient patients were identified and enrolled in the study; 43 nondeficient patients were also enrolled and were matched by age, clinical criteria of injury severity, and type of trauma. MAIN RESULTS: After severe injury (Injury Severity Score, > or =16), 50% of the deficient and 6.2% of nondeficient patients developed sepsis with positive bacterial blood cultures. In deficient patients, the frequency of bronchial (75%) and wound infections (25%) was also increased compared with nondeficient patients (32% and 0%). The durations of systemic inflammatory response syndrome, Sepsis Syndrome, and days on antibiotics were three times longer in deficient than in nondeficient individuals. However, adult respiratory distress syndrome occurred in 37% of both groups. Anemia was more severe in the deficient than nondeficient patients from day 10 posttrauma. On day 5, the peroxide content was doubled, apoptosis was decreased, and CD11b expression was increased in monocytes from deficient patients compared with cells from nondeficient patients. On day 5, the plasma interleukin (IL)-10 concentration was significantly lower in deficient than nondeficient patients, whereas tumor necrosis factor-alpha, IL-6, and IL-8 levels were similar. After moderate injuries (Injury Severity Score, 9-16), the deficiency was not associated with adverse clinical effects, and the trauma-induced changes in leukocyte function were similar in deficient and nondeficient patients. CONCLUSIONS: The common type A- G6PD deficiency predisposes septic complications and anemia in trauma patients after severe injuries as defined by an Injury Severity Score of > or =16. This adverse clinical course is accompanied by altered monocyte functions manifested as augmented oxidative stress, a decreased apoptotic response, increased cell adhesion properties, and a diminished IL-10 response.

Adult↗

PubMed2001

Inhibition of human immunodeficiency virus type 1 transcription by chemical cyclin-dependent kinase inhibitors.

Cyclin-dependent kinases (cdk's) have recently been suggested to regulate human immunodeficiency virus type 1 (HIV-1) transcription. Previously, we have shown that expression of one cdk inhibitor, p21/Waf1, is abrogated in HIV-1 latently infected cells. Based on this result, we investigated the transcription of HIV-1 in the presence of chemical drugs that specifically inhibited cdk activity and functionally mimicked p21/Waf1 activity. HIV-1 production in virally integrated lymphocytic and monocytic cell lines, such as ACH(2), 8E5, and U1, as well as activated peripheral blood mononuclear cells infected with syncytium-inducing (SI) or non-syncytium-inducing (NSI) HIV-1 strains, were all inhibited by Roscovitine, a purine derivative that reversibly competes for the ATP binding site present in cdk's. The decrease in viral progeny in the HIV-1-infected cells was correlated with a decrease in the transcription of HIV-1 RNAs in cells treated with Roscovitine and not with the non-cdk general cell cycle inhibitors, such as hydroxyurea (G(1)/S blocker) or nocodazole (M-phase blocker). Cyclin A- and E-associated histone H1 kinases, as well as cdk 7 and 9 activities, were all inhibited in the presence of Roscovitine. The 50% inhibitory concentration of Roscovitine on cdk's 9 and 7 was determined to be approximately 0.6 microM. Roscovitine could selectively sensitize HIV-1-infected cells to apoptosis at concentrations that did not impede the growth and proliferation of uninfected cells. Apoptosis induced by Roscovitine was found in both latent and activated infected cells, as evident by Annexin V staining and the cleavage of the PARP protein by caspase-3. More importantly, contrary to many apoptosis-inducing agents, where the apoptosis of HIV-1-infected cells accompanies production and release of infectious HIV-1 viral particles, Roscovitine treatment selectively killed HIV-1-infected cells without virion release. Collectively, our data suggest that cdk's are required for efficient HIV-1 transcription and, therefore, we propose specific cdk inhibitors as potential antiviral agents in the treatment of AIDS.

Cell Line↗

PubMed2001

Augmented TNF-alpha and IL-10 production by primed human monocytes following interaction with oxidatively modified autologous erythrocytes.

The presence of dysfunctional/damaged red blood cells (RBCs) has been associated with adverse clinical effects during the inflammatory response. The aim of this study was to elucidate whether oxidatively modified, autologous RBCs modulate monocyte cytokine responses in humans. Monocyte tumor necrosis factor alpha (TNF-alpha) and IL-10 production was measured in whole blood from healthy volunteers using ELISA and flow cytometry. Oxidatively modified RBCs (15 mM phenylhydrazine, 1 h, OX-RBC) or vehicle-treated RBCs (VT-RBC) opsonized by autologous serum were administered alone or in combination with one of three priming agents: E. coli lipopolysaccharide (LPS, 0.2 ng/ml), zymosan A (1 mg/ml), or phorbol 12-myristate 13-acetate (PMA, 50 ng/ml). OX-RBC or VT-RBC alone did not result in the release of TNF-alpha or IL-10. LPS, zymosan, and PMA caused marked and dose-dependent increases in TNF-alpha and IL-10 production. Addition of OX-RBC augmented the LPS-, zymosan-, and PMA-induced TNF-alpha release by approximately 100%. OX-RBC augmented LPS- and zymosan-induced IL-10 release by 400-600%. Flow cytometry analyses showed that monocytes were responsible for TNF-alpha and IL-10 production in whole blood. The presence of OX-RBC alone increased the complexity of CD14+ monocytes but caused no cytokine production. LPS alone induced cytokine production without altering cell complexity. After the combined (OX-RBC+LPS) treatment, monocytes of high complexity were responsible for TNF-alpha production. The presence of mannose or galactose (at 10-50 mM) did not alter the observed augmentation of cytokine production by OX-RBC, suggesting that lectin receptors are not involved in the response. These studies indicate that the interaction between damaged autologous erythrocytes and monocytes has a major impact on the cytokine responses in humans. An augmented cytokine production by the mononuclear phagocyte system may adversely affect the clinical course of injury and infections especially in genetic or acquired RBC diseases or after transfusions.

Adult↗

PubMed2000

Status of selected nutrients and progression of human immunodeficiency virus type 1 infection.

BACKGROUND: Immune function is highly dependent on nutritional status because the large mass and high rate of cellular turnover of the immune system make it a major user of nutrients. Furthermore, nutrient requirements may be increased during acute and chronic infections, including HIV-1 infection. OBJECTIVE: The current study was designed to assess relations among HIV-1 progression and 11 nutritional and demographic variables. DESIGN: The participants were 106 HIV-infected outpatients and 29 uninfected control subjects (n = 89 men and 46 women; age range: 35-57 y). The HIV-infected subjects represented a broad range of disease progression. RESULTS: We found lower concentrations of plasma and erythrocyte magnesium and of erythrocyte reduced glutathione beginning early in the course of HIV-1 infection. Significantly decreased hematocrit and increased serum copper concentration developed only late in the course of the disease. Statistically significant univariate associations were found between the CD4(+) T lymphocyte count and hematocrit, plasma magnesium concentration, and plasma zinc concentration. The lowest erythrocyte magnesium concentrations occurred in HIV-infected subjects who consumed alcoholic beverages. Independent variables that were significant joint predictors of CD4(+) cell count in multiple regression analyses were hematocrit and plasma free choline and zinc concentrations. These 3 factors together explained 43% of the variability in CD4(+) cell counts. CONCLUSION: The results provide evidence that compromised nutritional and antioxidant status begin early in the course of HIV-1 infection and may contribute to disease progression.

Adult↗

PubMed2000

Loss of G(1)/S checkpoint in human immunodeficiency virus type 1-infected cells is associated with a lack of cyclin-dependent kinase inhibitor p21/Waf1.

Productive high-titer infection by human immunodeficiency virus type 1 (HIV-1) requires the activation of target cells. Infection of quiescent peripheral CD4 lymphocytes by HIV-1 results in incomplete, labile reverse transcripts and lack of viral progeny formation. An interplay between Tat and p53 has previously been reported, where Tat inhibited the transcription of the p53 gene, which may aid in the development of AIDS-related malignancies, and p53 expression inhibited HIV-1 long terminal repeat transcription. Here, by using a well-defined and -characterized stress signal, gamma irradiation, we find that upon gamma irradiation, HIV-1-infected cells lose their G(1)/S checkpoints, enter the S phase inappropriately, and eventually apoptose. The loss of the G(1)/S checkpoint is associated with a loss of p21/Waf1 protein and increased activity of a major G(1)/S kinase, namely, cyclin E/cdk2. The p21/Waf1 protein, a known cyclin-dependent kinase inhibitor, interacts with the cdk2/cyclin E complex and inhibits progression of cells into S phase. We find that loss of the G(1)/S checkpoint in HIV-1-infected cells may in part be due to Tat's ability to bind p53 (a known activator of the p21/Waf1 promoter) and sequester its transactivation activity, as seen in both in vivo and in vitro transcription assays. The loss of p21/Waf1 in HIV-1-infected cells was specific to p21/Waf1 and did not occur with other KIP family members, such as p27 (KIP1) and p57 (KIP2). Finally, the advantage of a loss of the G(1)/S checkpoint for HIV-1 per se may be that it pushes the host cell into the S phase, which may then allow subsequent virus-associated processes, such as RNA splicing, transport, translation, and packaging of virion-specific genes, to occur.

CDC2-CDC28 Kinases↗

PubMed2000

Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected cells and its association with cyclin A/cdk2.

Human T-cell lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). T-cell transformation is mainly due to the actions of the viral phosphoprotein Tax. Tax interacts with multiple transcriptional factors, aiding the transcription of many cellular genes. Here, we report that the cyclin-dependent kinase inhibitor p21/waf1 is overexpressed in all HTLV-1-infected cell lines tested as well as in ATL and HAM/TSP patient samples. Tax was found to be able to transactivate the endogenous p21/waf1 promoter, as detected by RNase protection, as well as activate a series of wild-type and 5'-deletion constructs linked to a luciferase reporter cassette. Wild-type but not a mutant form of Tax (M47) transactivated the p21/waf1 promoter in a p53-independent manner and utilized a minimal promoter that contained E2A and TATA box sequences. The p21/waf1 protein was reproducibly observed to be complexed with cyclin A/cdk2 and not with any other known G(1), S, or G(2)/M cyclins. Functionally, the association of p21/cyclin A/cdk2 decreased histone H1 phosphorylation in vitro, as observed in immunoprecipitations followed by kinase assays, and affected other substrates, such as the C terminus of Rb protein involved in c-Abl and histone deacetylase-1 (HDAC1) regulation. Interestingly, upon the use of a stress signal, such as gamma-irradiation, we found that the p21/cyclin A/cdk2 complex was able to block all known phosphorylation sites on the Rb molecule. Finally, using elutriated cell cycle fractions and a stress signal, we observed that the HTLV-1-infected T cells containing wild-type Tax, which had been in early or mid-G(1) phase prior to gamma-irradiation, arrested in G(1) and did not undergo apoptosis. This may be an important mechanism for an oncogenic virus such as HTLV-1 to stop the host at the G(1)/S boundary and to repair the damaged DNA upon injury, prior to S-phase entry.

Animals↗

PubMed1999

Is depression associated with immune activation?

BACKGROUND: Some research immunologists have suggested that major depression amd chronic fatigue syndrome (CFS) are characterized by immune activation. To test this hypothesis, we compared immunological function in patients with major depression and in patients with CFS who developed major depression after the onset of CFS to that of sedentary healthy controls. METHODS: Subjects completed the Centers for Epidemiological Study-Depression (CES-D) questionnaire and allowed venisection. We performed flow cytometric analysis on 13 groups of white blood cells and used a reverse transcriptase PCR method to assay m-RNA of eight cytokines. RESULTS: CES-D scores were high in both patient groups and did not differ significantly. We found no evidence for immune activation in either patient group. Instead the data suggested immunological downregulation in depression. LIMITATIONS: Not all the subjects in the two patient groups were off antidepressants. CONCLUSIONS: The data indicate that immune activation is not necessary in depression--either alone or with CFS.

Adult↗

PubMed1999

Changes in immune parameters seen in Gulf War veterans but not in civilians with chronic fatigue syndrome.

The purpose of this study was to evaluate immune function through the assessment of lymphocyte subpopulations (total T cells, major histocompatibility complex [MHC] I- and II-restricted T cells, B cells, NK cells, MHC II-restricted T-cell-derived naive and memory cells, and several MHC I-restricted T-cell activation markers) and the measurement of cytokine gene expression (interleukin 2 [IL-2], IL-4, IL-6, IL-10, IL-12, gamma interferon [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]) from peripheral blood lymphocytes. Subjects included two groups of patients meeting published case definitions for chronic fatigue syndrome (CFS)-a group of veterans who developed their illness following their return home from participating in the Gulf War and a group of nonveterans who developed the illness sporadically. Case control comparison groups were comprised of healthy Gulf War veterans and nonveterans, respectively. We found no significant difference for any of the immune variables in the nonveteran population. In contrast, veterans with CFS had significantly more total T cells and MHC II+ T cells and a significantly higher percentage of these lymphocyte subpopulations, as well as a significantly lower percentage of NK cells, than the respective controls. In addition, veterans with CFS had significantly higher levels of IL-2, IL-10, IFN-gamma, and TNF-alpha than the controls. These data do not support the hypothesis of immune dysfunction in the genesis of CFS for sporadic cases of CFS but do suggest that service in the Persian Gulf is associated with an altered immune status in veterans who returned with severe fatiguing illness.

Adult↗

PubMed1998

Behavioral and demographic risk factors for transmission of human immunodeficiency virus type 1 in heterosexual couples: report from the Heterosexual HIV Transmission Study.

We compared 224 heterosexual couples who were discordant for human immunodeficiency virus (HIV) type 1 infection (one partner HIV infected) with 78 HIV-concordant couples (both partners HIV infected) to identify demographic and behavioral risk factors for HIV transmission. Among the 229 couples whose male partner was first infected, HIV-concordant couples had engaged in anal sex more frequently before and after knowing that the male was infected than had HIV-discordant couples. Pap smears of grade 2 or higher (inflammation) were more prevalent among the second-infected female partners in HIV-concordant couples than among uninfected women in discordant couples (58% vs. 23%; P < .001). Anal sex and unprotected vaginal sex after knowledge of a male partner's infection were significant correlates of concordance in a multivariate logistic model, as were ethnicity, marital status, and antiviral therapy. Ethnicity strongly predicted concordance, even after controlling for sexual risk behaviors and stage of disease.

Adult↗

PubMed1998

Single-blind, placebo phase-in trial of two escalating doses of selegiline in the chronic fatigue syndrome.

AIM: To perform a clinical trial of selegiline in 25 patients with chronic fatigue syndrome (CFS) where patients were told they would receive placebo or active agent at different times during the 6-week trial. We chose selegiline, a specific monoamine oxidase (MAO) B receptor inhibitor, because a prior trial of lowdose phenelzine, a nonspecific MAO inhibitor, showed a small but significant therapeutic effect. METHODS: Questionnaires comprised of 19 tests of mood, fatigue, functional status and symptom severity were collected at the start and end of the trial as well as 2 weeks after its start. The trial was done in three 2-week blocks: in the first, 2 placebo pills were given per day; in the next, one 5-mg tablet of agent and one placebo were given per day, and in the last, a 5-mg tablet of agent was given twice a day. The plan was to compare the changes in the 19 tests during the placebo phase to those found in the active treatment phase in 19 patients completing the trial. FINDINGS: Significant improvement in 3 variables-tension/anxiety, vigor and sexual relations-was found. A significant pattern of improvement compared to worsening was found for the 19 self-report vehicles during active treatment as compared with placebo treatment. Evidence for an antidepressant effect of the drug was not found. CONCLUSIONS: Selegiline has a small but significant therapeutic effect in CFS which appears independent of an antidepressant effect.

Activities of Daily Living↗

PubMed1998

[New evidence of the antigenic relation between the viruses of epidemic neuropathy and the human nervous system. A study of the immune cellular response in patients with epidemic neuropathy and controls. A review of the topic].

A series of experiments was made at the Virology Department of the "Pedro Kourí" Institute of Tropical Medicine aimed at obtaining new evidences on the possible antigenic relations existing between the viruses isolated from patients with epidemic neuropathy and the structures of the human nervous system. According to the results it may be finally inferred that the persistence and/or autoimmunity may be considered as mechanisms through which the studied viruses participate in the etiopathogenesis of the epidemic neuropathy in Cuba. For future experiments it is very important to identify the possible viral epitopes involved in the molecular mimicry that are responsible for the probable autoimmune mechanisms or for the viral persistence.

Adult↗

PubMed1997

The effect of total lymphoid irradiation and low-dose steroids on T lymphocyte populations in multiple sclerosis: correlation with clinical and MRI status.

We have monitored the cell surface phenotypic changes occurring in T, B and NK cells of chronic progressive multiple sclerosis (MS) patients after total lymphoid irradiation (TLI) plus low-dose prednisone (TLI-LDP) therapy in comparison to sham TLI-LDP. TLI-LDP resulted in a marked reduction in the relative and absolute number of total CD3+ T cells, CD4+ helper T cells, CD4+ CD45RA+ naive T cells and CD19+ B cells for at least 1 year after treatment. No change occurred in the percent CD8+ T cells although the number of these cells declined after radiotherapy. The CD4/CD8 T cell ratio was also decreased. The relative percent of CD16+ NK cells increased steadily after TLI-LDP while the number of NK cells transiently declined but returned to baseline values 1 year later. An increase in the percent of CD2+ CD3- cells and a decrease in their number after therapy was also observed. In contrast, no significant changes in the number of T, B or NK cells were seen in the MS patients receiving sham TLI-LDP. These results provide further evidence that radiotherapy causes a reduction of immunocompetent T and B cells and that a population of possibly NK cells and/or immature T cells appears to be repopulating the circulation after TLI. In addition, a correlation was observed between alterations in lymphocyte populations and the presence or absence of contrast enhancing or new T2 lesions on brain magnetic resonance imaging (MRI) in the TLI-LDP treated MS patients. Patients devoid of contrast enhancing or new T2 lesions had a decreased percentage of CD3+ and CD4+ T cells prior to therapy and at six months following TLI-LDP compared to patients with such lesions. An association was also observed between stability in disease activity as determined on the Expanded Disability Status Scale and relative values of CD3 T cells.

Adult↗

PubMed1997

Evaluation of a method for counting absolute numbers of cells with a flow cytometer.

We evaluated a method for performing absolute cell counts of lymphocyte populations with a flow cytometer. In this method, TruCount, test tubes that contain a known number of brightly fluorescent polystyrene beads are provided by the manufacturer. Whole anticoagulated blood is accurately pipetted into the tubes and mixed with fluorochrome-labeled monoclonal antibodies, the erythrocytes are lysed, and this mixture is analyzed on the flow cytometer. Absolute counts of lymphocyte subsets are calculated by determining the ratio of beads to the cell population of interest and then multiplying this ratio by the number of beads in the tube. We found this method to be reproducible. The values we obtained by the TruCount method were 5 to 10% higher than those obtained by conventional methods (flow cytometry and automated hematology) used to determine absolute numbers of cells. We believe that these differences are due to the methods of determining absolute cell counts and not to faulty identification of lymphocyte subsets.

Adolescent↗

PubMed1994

Induction of autologous mixed lymphocyte culture responses by myelin basic protein-reactive T cell clones.

Myelin basic protein is an autoantigen present in the central nervous system suspected to be the target of destruction in multiple sclerosis. In the present study, we have demonstrated that T cell clones specific for myelin basic protein have the ability to induce proliferative responses in resting T lymphocytes in the autologous mixed lymphocyte culture (AMLC). T cell recognition of the AMLC stimulatory determinants on the clones required the presence of autologous monocytes. T lymphocytes primed against an autologous myelin basic protein-specific T cell clone displayed specific memory responses against the original stimulating clone and failed to exhibit secondary reactivity to 'sister' myelin basic protein-reactive clones and to autologous T cell clones specific for another antigen. Monoclonal antibodies specific for class II HLA-DR antigens inhibited secondary AMLC responses. Modulation of the T cell receptor from the surface of the clones decreased their AMLC stimulatory ability. These results indicate that idiotype-like determinants on the T cell receptor of autoantigen-specific T cell clones are capable of triggering anti-idiotypic T cell responses.

Cells, Cultured↗

PubMed1994

Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people.

A placebo-controlled double-blind trial of the effects of daily micronutrient supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skin test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned to placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12 mo of micronutrient ingestion. For the micronutrient group, there were statistically significant increases at 6 and/or 12 mo in the mean serum concentrations of ascorbate, beta-carotene, folate, vitamin B-6, and alpha-tocopherol. There was a significant increase at 12 mo in the number of subjects in the placebo group with one or more low concentrations. DHST responses to a panel of seven recall antigens were significantly increased at 12 mo in the micronutrient group but not the placebo group. This study demonstrates that daily supplementation with low-to-moderate doses of micronutrients can prevent low concentrations of some micronutrients and can improve DHST responses in healthy, independently living older adults.

Aged↗

PubMed1993

Enzyme immunoassay for detection of human immunodeficiency virus-specific immunoglobulin A antibodies.

Early diagnosis of human immunodeficiency virus (HIV) infection may be difficult in adults with acute or recent HIV infection and in infants with perinatally acquired HIV. Detection of HIV-specific immunoglobulin A (IgA) antibodies in infant serum by Western blot (immunoblot) has been suggested as a reliable method to identify HIV-infected infants, especially those over the age of 6 months, and as an adjunct to diagnosis of acute HIV infection in adults. We developed a simple enzyme immunoassay for detection of HIV-specific IgA, using standard commercially available reagents. Enzyme immunoassay was comparable to Western blot for detection of HIV-specific IgA in sera from adults (n = 216), older children (n = 49), and infants born to HIV-infected mothers (n = 65). Specificity was 100% and sensitivity ranged from 80 to 92%. IgA-enzyme immunoassay is a simple, highly sensitive method for detection of HIV-specific IgA antibodies and is easily adapted to the standard clinical laboratory.

Adolescent↗

PubMed1992

Lymphocyte subsets in healthy children during the first 5 years of life.

OBJECTIVE: To assess whether relative and absolute values of CD4 and CD8 lymphocytes and CD4/CD8 ratio change in relation to age, and to estimate the fifth and 95th percentiles for these values in children of various ages. PATIENTS AND METHODS: Phenotypic analysis of lymphocyte subsets was performed on blood samples from 208 healthy children, aged 1 through 59 months, using standard flow cytometric techniques. RESULTS: Regression analysis demonstrated that CD4 and CD8 lymphocyte counts declined significantly with advancing age (P less than .000001 and P = .03, respectively). Since CD4 and CD8 counts depend on total lymphocyte count, the percentage of total lymphocytes of each phenotype was also analyzed and demonstrated that the CD4 percentage was highly age dependent (P less than .000001). The CD8 percentage increased with age (P = .0001) but not as much as the CD4 percentage decreased. Median CD4 counts (fifth and 95th percentiles) for children 2 through 3, 4 through 8, 12 through 23, and 24 through 59 months of age were 2.83 (1.46 to 5.11), 2.95 (1.69 to 4.61), 2.07 (1.02 to 3.60), and 1.80 (0.90 to 2.86) x 10(9)/L, respectively. CONCLUSION: Healthy children's CD4 lymphocyte counts are considerably higher than previously established adult values. These data demonstrate that age is an important consideration in interpretation of lymphocyte subsets in children. This may be especially relevant in children who are infected with the human immunodeficiency virus, where CD4 lymphocyte values play a central role in monitoring disease progression and determining thresholds for medical interventions.

CD4-CD8 Ratio↗