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Biomedical subjects

I Hannet

Publications and source records attributed to I Hannet.

7 recordsLinked to original sources

The immune profile of multiple sclerosis: T-lymphocyte effects predominate over all other factors in cyclophosphamide-treated patients.

It is widely believed that multiple sclerosis is a T-cell mediated autoimmune disease associated with abnormalities in immunoregulation. This large, prospective study evaluated the lymphocyte immunophenotypic profile of 246 MS patients, divided clinically into a remitting/relapsing group (n = 176) and a progressive group (n = 70), and compared their results to those of 117 healthy controls. All patients were found to have significantly elevated percentage and absolute numbers of IL2R+CD3+ cells as well as depressed percentages of CD45RA+CD4+ cells. However, when the factor of treatment with cyclophosphamide (CY) versus no treatment or treatment with other agents was used to group patients, dramatic declines in both percentages and absolute numbers of CD45RA+CD4+ cells were discovered. These declines were associated specifically with CY and and could be explained by this factor independent of the clinical state of the patient. The effects were seen in patients undergoing current treatment or in those exposed to CY in the near or remote past. These findings highlight the confounding effect of specific treatments on the immune profile of MS patients groups and suggest that there may be important implications for cellular function and clinical outcome in these and other patient groups.

Adult

An optimized method for routine HLA-B27 screening using flow cytometry.

Flow cytometry and monoclonal antibodies are promising tools for HLA-antigen detection. Previous approaches have been hampered by the lack of a carefully standardized system for calibration and sample analysis. A new system for HLA-B27 screening was developed using a FACScan flow cytometer, software for automated calibration and analysis, calibration beads, and the anti-HLA-B27-FITC/anti-Leu4-PE (CD3) monoclonal antibodies. The median fluorescence channel result for the HLA-B27-FITC signal of CD3+ T lymphocytes is compared to a decision marker. Values lower than this threshold are read as HLA-B27 negative and those above are recommended for retesting with the classic microcytotoxicity assay on the presumption of HLA-B27 positivity. The anti-HLA-B27 antibody reacts with all six HLA-B27 subtypes and shows a weaker binding to HLA-B7. The screening test results were compared with those from the microcytotoxicity assay for HLA-typing in studies involving several European centers. The observed sensitivity was 100% (95% Cl:98.6-100) and the specificity was 97.4% (95% Cl: 96.4-98.3). Other performance studies verified the reproducibility and reliability of results obtained with the screening system.

Anticoagulants

Age-related changes in human blood lymphocyte subpopulations. II. Varying kinetics of percentage and absolute count measurements.

A reference range for lymphocyte populations, with particular emphasis on T lymphocyte subsets, was obtained for normal individuals covering age cohorts from birth through adulthood. This report confirms and extends findings from a developmental reference range published earlier (1). Absolute numbers of WBC, lymphocytes, and T, B, and NK subsets decline significantly during childhood. However, differences in the rate of decline of certain lymphocyte subsets leads to discordance between absolute numbers and percentages. Those lymphocyte subsets which decline less rapidly with age than the total lymphocyte count will show an increase in percentage, whereas those which decline more rapidly will show further declines in percentage values. T cell percentages were seen to increase over time whereas B cell percentages decline. Markers of immaturity such as CD45RA on CD4 cells and CD38 on CD8 cells declined in both percentages and absolute numbers. Activation markers, such as HLA-DR on CD8 cells and IL2-R on CD3 cells, increased in percentages with time but changed inconsistently in cell number from infancy to adulthood. These findings extend the lymphocyte references range to markers thought to be informative in various disease states, including HIV infection.

Adolescent

Lymphocyte subsets in a large cohort of patients with systemic lupus erythematosus.

In search of markers of disease activity in patients with SLE we have investigated blood lymphocyte subsets from a large cohort of patient. Seventy-one patients were studied using a well-defined panel of fluorescent monoclonal antibodies which recognize the major T, B and NK lymphocyte subsets and activated cells. Flow cytometry was used with standard automated software. Overall, SLE patients were lymphopenic. The proportion of activated T cells was increased and NK cells were decreased in both proportion and absolute numbers (P < 0.001). This decrease was more pronounced in the more active patients. None of the T cell activation markers was shown to distinguish different degrees of disease activity. However, the percentage of NK cells was significantly reduced in active disease states (P < 0.01). Decreased numbers of NK cells could potentially reduce the resistance of SLE patients to infectious organisms.

Adult

Age-related changes in human blood lymphocyte subpopulations.

Flow cytometric analysis of major lymphocyte populations and their subsets reveals age-related changes in the cellular human immune system. Immunophenotypic markers were evaluated in 110 normal pediatric subjects, divided into groups of newborn infants, infants aged 2 days to 11 months, and children aged 1 to 6 years and 7 to 17 years; results were then compared with those obtained from 101 normal adults aged 18 to 70 years. Comparisons among age groups from newborn infants through adults reveal progressive declines in the absolute numbers of leukocytes, total lymphocytes, and T, B, and natural killer (NK) cells. The percentages of T cells within the total lymphocyte population increase with age, in both CD4+ and CD8+ subsets. Percentages of B and NK cells are higher in newborn infants than in adults. The expression of the activation markers interleukin-2R and HLA-DR on T cells increases with age, as does the NK-associated expression of CD57 on CD8 cells. The proportions of B lymphocytes that coexpress CD5 or CDw78 decrease with age, whereas expression of Leu-8 and CD23 increases. The proportion of CD4 cells bearing the CD45RA and Leu-8 markers is consistently lower in adults than in children. These data may serve as a reference range for studies of pediatric subjects.

Adolescent

Expression of activation antigens, HLA-DR and CD38, on CD8 lymphocytes during HIV-1 infection.

OBJECTIVE: To study the expression of the activation markers human leukocyte antigen (HLA)-DR and CD38 antigen on CD8+ T-lymphocytes in HIV-infected subjects and HIV-negative controls. DESIGN: Two- and three-colour flow-cytometric analysis. METHODS: Fresh peripheral venous blood was obtained from 16 HIV-infected subjects, representing four different stages of HIV disease, and from six HIV-negative controls. Three-colour lymphocyte immunophenotyping was performed using peridinyl chlorophyll-A protein (PerCP)-conjugated anti-CD8 monoclonal antibody (MAb) in combination with anti-HLA-DR (phycoerythrin) and anti-CD38 (fluorescein isothiocyanate) MAb. RESULTS: The relative percentage of the lymphocyte populations thus defined differed between HIV-negative and HIV-positive subjects and between HIV-infected subjects at different clinical stages of disease. Simultaneous expression of HLA-DR and CD38 within the CD8 T-lymphocyte compartment increased from 8% in controls to 49% in asymptomatic HIV-infected subjects (P less than 0.005). Symptomatic patients differed from asymptomatic seropositives by a further increase in the HLA-DR+ CD38+ CD8 subset. In AIDS patients, the HLA-DR+ CD38- CD8 subset decreased (P less than 0.05) and the HLA-DR- CD38+ CD8 subset increased (P less than 0.05), compared with the other HIV disease stage patients. CONCLUSION: There is a stage-associated pattern of HLA-DR and CD38 expression on CD8 T-lymphocytes during HIV infection; specific phenotypic patterns may have functional correlates in the host response to the virus.

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