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Biomedical subjects

L Kestens

Publications and source records attributed to L Kestens.

At least 55 records · Page 3Linked to original sources
PubMed1994

Prospective comparison of mother-to-child transmission of HIV-1 and HIV-2 in Abidjan, Ivory Coast.

OBJECTIVE: To compare mother-to-child transmission of human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2, respectively) and to assess the impact of maternal HIV-1 and HIV-2 infections on child survival. DESIGN: Prospective cohort study. SETTING: Maternal and child health center in a lower socioeconomic class district of Abidjan, Ivory Coast. PARTICIPANTS: A total of 18,099 women delivering between 1990 and 1992 were tested for HIV-1 and HIV-2 antibodies. A cohort of 613 pregnant women and their infants was followed prospectively (138 women reactive to HIV-1, 132 reactive to HIV-2, 69 reactive to both viruses, and 274 HIV-seronegative). MAIN OUTCOME MEASURES: Rates of perinatal transmission for HIV-1, HIV-2, and both viruses, determined from results of serological and polymerase chain reaction tests on children; survival of infants born to HIV-1-positive, HIV-2-positive, dually reactive, and HIV-seronegative women. RESULTS: Of the 18,099 women tested, 9.4% were reactive to HIV-1 alone, 1.6% to HIV-2 alone, and 1.0% to both viruses. The rate of perinatal transmission of HIV-1 was 24.7% (95% confidence interval [CI], 15.8% to 33.7%), compared with 1.2% (95% CI, 0.0% to 3.5%) for HIV-2 (relative risk, 21.3; 95% CI, 2.9 to 154.3). Overall, 19.0% (95% CI, 9.0% to 29.0%) of infants of dually reactive women became infected; of the 11 children concerned, 10 were infected with HIV-1 and one with HIV-1 and HIV-2. Infants of HIV-seropositive mothers had a reduced survival; mortality rates were 15.1, 13.0, 6.5, and 3.4 deaths per 100 child-years, respectively, for children of HIV-1-positive, dually reactive, HIV-2-positive, and HIV-seronegative women. CONCLUSIONS: The rate of perinatal transmission of HIV-2 (1.2%) was much lower than the rate of perinatal transmission of HIV-1 (24.7%), and this was associated with more favorable survival for infants of HIV-2-infected mothers. Dually reactive women could transmit both viruses, although transmission usually involved HIV-1 only. Public health guidelines should incorporate advice that perinatal transmission of HIV-2 is rare.

AIDS Serodiagnosis↗
PubMed1994

Contribution of tuberculosis to slim disease in Africa.

OBJECTIVES: To assess the contribution of tuberculosis to the aetiology of the HIV wasting syndrome (slim) in Africa, a condition usually considered an enteropathy. METHODS: Clinical examination and representative necropsy study of adult patients positive for HIV. SETTING: Hospital medical wards in Abidjan, Ivory Coast. SUBJECTS: Adults positive for HIV. MAIN OUTCOME MEASURES: CD4 T lymphocyte counts before death, clinical and anthropometric data, and gross and microscopic pathology. RESULTS: Necropsy was done on 212 HIV positive adults. Tuberculosis was found in 41 of 93 with the clinical HIV wasting syndrome and in 32 of 119 without (odds ratio 2.1, 95% confidence interval 1.2 to 4.0). A significant association existed between the prevalence of tuberculosis at necropsy and the degree of cadaveric wasting (no wasting 25% (15/59); moderate wasting 40% (23/58); skeletal wasting 44% (42/95); P = 0.02). Wasting was also associated with a history of chronic diarrhoea, but no association existed between diarrhoea and tuberculosis. Median CD4 T lymphocyte counts were lowest in wasted patients irrespective of findings at necropsy and in those with chronic diarrhoea (< 60 x 10(6)/l). CONCLUSION: Wasting and chronic diarrhoea are late stage manifestations of HIV disease in Africa. The importance of tuberculosis as a contributing factor in the pathogenesis of the slim syndrome has been underestimated. In nearly half of patients dying with severe wasting, tuberculosis was the dominant pathological finding.

Adolescent↗
PubMed1994

Binding of adenosine deaminase to the lymphocyte surface via CD26.

The relationship between CD26/dipeptidyl peptidase IV, an ectopeptidase involved in T cell activation, and the binding protein for adenosine deaminase (ADAbp) was studied. Monoclonal antibodies (mAb) against CD26 and ADAbp, respectively, showed a similar binding profile on various lymphocyte subsets from the peripheral blood. The adenosine deaminase (ADA) itself blocked the binding of a specific set of anti-CD26 mAb (among these the anti-TA5.9 mAb) on lymphocytic CD26; ADA also hindered the binding of soluble CD26 to the same immobilized anti-CD26 mAb. In addition, the interaction between immobilized ADA and purified CD26/DPP IV was inhibited by the anti-TA5.9 mAb. ADA did not inhibit the specific peptidase activity of CD26. Neither soluble nor immobilized ADA was able to down-modulate CD26 on the lymphocyte surface. Our data thus confirm the identity between ADAbp and CD26 and identify some epitopes, crucial in the binding of ADA to CD26.

Adenosine Deaminase↗
PubMed1994

The interleukin-2 receptor subunit expression and function on peripheral blood lymphocytes from HIV-infected and control persons.

The expression of interleukin-2 receptor (IL2R) was studied on circulating lymphocytes from HIV-infected (HIV+) and control subjects, using chain-specific monoclonal antibodies and indirect immunofluorescence flow cytometry. The IL2R alpha chain expression was decreased on CD4 and CD8 T cells from HIV+ persons compared to controls. Conversely, beta chain expression was enhanced on both T cell subsets from the patients. IL2R-subunit levels were similar on natural killer cells from patients and controls. To evaluate the function of IL2R, we investigated to what extent IL2 could induce CD69, an early activation marker of lymphocytes. A dose-dependent increase of CD69 expression was observed on T and NK cells from all subjects. The upregulation of CD69 was similar on CD4 T and NK cells from patients and controls, but was more pronounced on CD8 T cells from HIV+ compared to HIV- subjects. Based on inhibition studies, both the alpha and the beta chain contributed to the IL-2-induced CD69 expression on CD4 T cells, pointing to involvement of the high-affinity receptor. The early activation of CD8 T cells and NK cells was mainly dependent on the intermediate-affinity receptor. We conclude that significant changes in IL2R alpha and beta chain expression on circulating T cells occur after HIV infection, but that early activation through IL2 is preserved or enhanced, even in advanced stages.

Adult↗
PubMed1994

Deficient T-cell responses in non-responders to hepatitis B vaccination: absence of TH1 cytokine production.

The inability to mount a protective level (> or = 10 IU/l) of hepatitis B surface antigen (HBsAg)-specific antibodies after vaccination is presumably the consequence of a defect in the cellular immune regulation. We compared the in vitro immune responses of peripheral blood mononuclear cells (PBMC) from high, intermediate and non-responders, after stimulation with recombinant HBsAg. The absence of a proliferative response in non-responders was not reversed by removal of CD8+ T cells, indicating that HBsAg-specific CD8+ T-cell-induced suppression was not the underlying cause of non-responsiveness. Non-responders did not produce cytokines after HBsAg stimulation. High responders displayed a typical Th1-like profile since their PBMC produced interleukin-2 (IL-2) and gamma-interferon (IFN gamma) and no detectable IL-4 or IL-5 upon stimulation with HBsAg.

Adult↗
PubMed1994

Idiopathic CD4+ T-lymphocyte depletion in a west African population.

OBJECTIVE: To assess the frequency of CD4+ T-lymphocyte depletion in selected populations in West Africa and to determine whether an association exists between AIDS-like illnesses and CD4+ T-lymphocytopenia in HIV-negative individuals. DESIGN: Retrospective review of databases and prospective case-control study. SETTING: Project RETRO-CI, an AIDS research project in Abidjan, Côte d'Ivoire, a University Hospital and tuberculosis treatment and maternal and child health centres in Abidjan. METHODS: We conducted a retrospective review of CD4+ T-lymphocyte counts performed between 1991 and 1992 on hospitalized medical patients, outpatients with tuberculosis, and women participating in a study of HIV-1 and HIV-2 mother-to-child transmission. A prospective case-control study was conducted in 1992 to examine the relationship between HIV-negative CD4+ T-lymphocyte depletion and wasting syndrome (wasting and chronic diarrhoea and/or chronic fever). RESULTS: In the retrospective data review, CD4+ T-lymphocyte counts < 300 x 10(6)/l were found in 9.6% of 115 HIV-negative hospitalized patients, in 4.2% of 312 ambulatory tuberculosis patients, and in 0.4% of 263 healthy women after delivery. In the case-control study, no association was found between CD4+ T-lymphocyte depletion in HIV-negative individuals and the presence of wasting syndrome. Increased mortality in HIV-negative individuals was associated with wasting but not with reduced CD4+ T-lymphocyte counts. In contrast, a trend existed for increased mortality with increasingly severe CD4+ T-lymphocyte depletion in HIV-positive patients. Tuberculosis was the most frequently proven or suspected diagnosis in HIV-negative individuals with wasting and CD4+ T-lymphocytopenia. CONCLUSIONS: In the absence of HIV infection, CD4+ T-lymphocytopenia is uncommon (< 1%) in West African asymptomatic individuals but is more frequent in those with tuberculosis (4%) and hospitalized patients (10%). CD4+ T-lymphocytopenia in HIV-negative individuals was not associated with wasting syndrome or increased mortality. There was no evidence for frequent, clinically relevant immune deficiency other than that associated with HIV infection.

Adult↗
PubMed1994

Expression patterns of Fc gamma receptors, HLA-DR and selected adhesion molecules on monocytes from normal and HIV-infected individuals.

The expression and co-expression profiles of functionally important monocyte surface markers were compared between control and HIV+ individuals using combined physical gating and dim CD4 expression to delineate the monocytes. The Fc gamma RII (CD32), the MHC class II antigen HLA-DR and the adhesion molecules CD11a (LFA-1 alpha), CD18 and CD54 (ICAM-1) showed an unimodal distribution. Of these markers, CD11a and HLA-DR were up-regulated in the HIV+ subjects compared with controls. The expression levels of the adhesion molecules correlated with each other in both patients and controls. The CD11b (CR3-alpha), CD14, Fc gamma RI, and Fc gamma RIII markers were bimodally distributed. Compared with controls, monocytes from seropositives contained fewer CD14bright+ cells, an equal proportion of Fc gamma RIbright+ cells, but twice as many Fc gamma RIII+ cells. The expression level of Fc gamma RI and CD11b within their brightly positive subset increased as CD4 T cells decreased. Both in patients and controls, co-expression of bright CD11b, CD14 and Fc gamma RI was shown, whereas the Fc gamma RIII+ cells were negative or dim positive for the former triad. We conclude that the expression of two Fc gamma R (I and III), of the adhesion molecules CD11a and CD11b and of HLA-DR showed particular alterations on monocytes from HIV+ subjects. The relationship of these phenotypic observations with altered cytokine profiles and altered monocyte function is discussed.

Antigens, CD↗
PubMed1994

Selective increase of activation antigens HLA-DR and CD38 on CD4+ CD45RO+ T lymphocytes during HIV-1 infection.

Infection with HIV results in a progressive depletion of CD4+ T cells and leads to significant in vivo lymphocyte phenotype changes. In this regard, the expression of HLA-DR and CD38 on CD8+ T cells has been shown to increase dramatically with disease progression. We investigated the expression of both activation markers on CD4+ T cells in HIV-1-infected subjects at different clinical stages of infection and compared the in vivo activation of CD4+ T cells with parameters of viral activity and CD8+ T cell activation. Fresh peripheral venous blood was obtained from 54 HIV-infected subjects and from 28 uninfected healthy controls. Three-colour immunophenotyping of the CD4+ T cell subset showed that the proportion of CD4+ T cells expressing HLA-DR (10% in HIV-negative controls) or CD38 (62% in HIV-negative controls) was higher in asymptomatic (P < 0.05 for CD38) and symptomatic (P < 0.001 for HLA-DR and CD38) HIV-infected subjects than in controls, whereas the proportion of CD4+ T cells expressing CD45RO (54% in controls) remained relatively unchanged. Simultaneous expression of HLA-DR and CD38 on CD4+ T cells increased from 2.3% in controls to 11% (P < 0.001) in asymptomatic and 22% (P < 0.001) in symptomatic HIV-infected subjects. This relative increase of CD38 and HLA-DR expression occurred mainly on CD4+ T cells co-expressing CD45RO. Changes in expression of HLA-DR and CD38 on CD4+ T cells correlated with similar changes on CD8+ T lymphocytes, with the presence of HIV antigen in the circulation, and with the disease stage of HIV infection.

ADP-ribosyl Cyclase↗
PubMed1994

[Validity of an ELISA test for CD4+ T lymphocyte count and validity of total lymphocyte count in the assessment of immunodeficiency status in HIV infection].

A newly available commercial ELISA (TRAx CD4, T Cell Diagnostics USA) for enumerating CD4+ T lymphocytes has been evaluated with blood samples of 105 HIV seropositive and 6 seronegative subjects. Results from the flow cytometric analysis were used as reference. The sensitivity and specificity of the ELISA to identify HIV seropositive subjects having less than 200 CD4+ T lymphocytes/microliters were assessed and studied using the ROC curve. The reproducibility of the ELISA test was analyzed on 40 samples. The results of the ELISA correlated well with these of the flow cytometric analysis (r = 0.79, p < 0.001). However, the ELISA test tends to overestimate the true CD4 count in HIV seropositives. This overestimation could not be explained by the aspecific contribution of monocytic CD4. The threshold for identifying HIV seropositive subjects with less than 200 CD4+ T lymphocytes with a maximum sensitivity and specificity was determined with ROC curve and equalled 400 cell equivalents with the ELISA (sensitivity and specificity were equal to 80%) and 1,450 lymphocytes/microliters with the total absolute lymphocyte count (sensitivity and specificity were equal to 75%). Using this curve, a threshold of 300 cell equivalents for the ELISA test and of 1,100 lymphocytes/microliters for the absolute lymphocyte count was shown to maximize the specificity (> 95%) without a significant loss of sensitivity.

CD4-Positive T-Lymphocytes↗
PubMed1993

Immunological parameters during treatment with ditiocarb (Imuthiol).

OBJECTIVES: To examine the effect of ditiocarb (DTC) treatment on immunological parameters of HIV infection. Immunophenotyping included CD4+ T-cell counting and the analysis of activation markers on CD8+ T cells. Anti-CD3-induced proliferation and anti-CD3-mediated cytotoxicity were monitored as indexes of T-cell function. In addition to the clinical evolution, HIV antigen and anti-p24 levels were monitored during treatment. DESIGN: In this double-blind, placebo-controlled study, 50 HIV-seropositive patients belonging to all clinical disease stages were randomized to treatment with DTC or placebo and followed for 4 months. METHODS: Immunophenotyping on whole blood was performed by flow cytometry, using combinations of anti-CD8 with anti-CD4, anti-HLA-DR, anti-CD38, anti-CD45RO and anti-CD57. Patient lymphocytes were freshly assayed for cytolytic capacity against OKT3-coated targets. T-cell proliferation was measured after 3 days of OKT3-stimulation. RESULTS: No effect was observed on CD4 and CD8+ T-cell counts or on CD8+ T-cell activation markers, except for a selective increase in HLA-DR expressing CD8 cells in the DTC-treated group. Decline in anti-CD3-induced T-cell proliferation and rise in anti-CD3-mediated T-cell cytotoxicity were observed in the DTC and placebo groups. No effect on HIV antigen and anti-p24 antibody titres was observed. The incidence of clinical complications was similar in each group. CONCLUSION: No beneficial immunomodulatory effect of DTC was demonstrated.

Adult↗
PubMed1993

Evaluation of two staging systems for HIV infection for use in developing countries.

OBJECTIVE: To evaluate the clinical axis of the World Health Organization (WHO) clinical staging system and the modified WHO staging system proposed by Montaner et al. using the lymphocyte strata > 1500, 1500-1000 and < 1000 cells x 10(6)/l. DESIGN: Cross-sectional study. PATIENTS: Four hundred and fifteen consecutive patients with HIV infection attending three HIV reference centres in Belgium. METHODS: Absolute CD4 lymphocyte counts were compared between stages within the two staging systems. RESULTS: Median CD4 lymphocyte counts decreased with increasing stage of disease in both staging systems. Differences in median CD4 lymphocyte counts between stages of each staging system were statistically significant (Kruskal-Wallis one-way analysis of variance, P < 0.001). The WHO clinical stage 1 and the modified WHO stage I had positive predictive values of 56 and 58%, respectively, for identifying patients with CD4 lymphocyte levels > 500 cells x 10(6)/l. The WHO clinical stage 4 and the modified WHO stage IV had positive predictive values of 79 and 80%, respectively, for identifying patients with CD4 lymphocyte levels < 200 cells x 10(6)/l. CONCLUSIONS: The WHO clinical staging system or a modified version of this system using lymphocytes stratification may be a good alternative in developing countries to the CD4 lymphocyte count-based HIV staging system used in the developed world. Cohort studies in developing countries are needed to assess their prognostic value.

CD4-Positive T-Lymphocytes↗
PubMed1993

Decreased expression of the memory marker CD26 on both CD4+ and CD8+ T lymphocytes of HIV-infected subjects.

Using a novel anti-CD26 (or anti-dipeptidyl peptidase IV) monoclonal antibody, we showed that the absolute numbers and the proportions of T4 and T8 cells expressing CD26 were significantly lower in HIV-infected persons than in controls. The absolute number of CD26+ T4 cells decreased according to disease progression, whereas the number of CD26+ T8 cells was low throughout all clinical stages. These trends were similar in CD26 dim and bright positive T-cell subsets. In both controls and HIV-positive subjects, the CD26 bright positive T cells were restricted to the CD45RO+ subset and preferentially co-expressed CD25 but largely lacked HLA-DR and CD38. Recall antigen-responsive cells from seronegative individuals were shown to co-express CD26 and CD45RO. The deficient CD26 expression on T8 cells from HIV-infected subjects could be normally upregulated after in vitro stimulation. In contrast to decreased T-cell-bound CD26, the enzymatic activity of plasma CD26/dipeptidyl peptidase IV was unchanged in HIV-infected patients compared with controls. We conclude that HIV infection leads to a deficient in vivo co-expression of CD26 bright and CD45RO on T cells. We speculate that this deficiency might play a part in the decrease of immunological memory during HIV infection.

ADP-ribosyl Cyclase↗
PubMed1992

Immune complexes and antibody levels in blisters over human leprosy skin lesions with or without erythema nodosum leprosum.

Erythema nodosum leprosum (ENL) is a serious complication of lepromatous leprosy, affecting skin and peripheral nerves in a large percentage of these patients, and is presumed to result from spontaneous immunologic changes. Its pathogenesis is poorly understood, although histopathologic features have suggested immune complex (IC)-mediated injury. Abundant circulating antibody is present but no convincing correlation has been established between circulating IC and ENL. We have examined cutaneous leprosy lesions in vivo using blisters induced by prolonged gentle suction to determine whether or not IC are demonstrable in lesions with or without ENL, using an IC assay based on monoclonal rheumatoid factor binding. We also examined whether antibodies involved in such IC are produced locally or reach the skin via the circulation. Surprisingly large quantities of IC were found in ENL lesions, and in some cases the quantities were significantly higher than in matching serum. Total IgG, IgA, and IgM in the skin were not higher than expected, however. Attempts to demonstrate increases in intracutaneous levels of specific anti-Mycobacterium leprae antibodies were unsuccessful. This is the first report of the demonstration of IC in suction blister fluid. The results indicate that large quantities of IC may be present in cutaneous leprosy lesions and are consistent with the hypothesis that they are formed in situ when circulating antibody combines with antigen in the skin. The nature of the antigen in these IC remains undefined.

Antibodies↗
PubMed1992

Isolation and characterization of a new chimpanzee lentivirus (simian immunodeficiency virus isolate cpz-ant) from a wild-captured chimpanzee.

OBJECTIVE: To assess the prevalence of infection with simian immunodeficiency virus (SIV) isolate cpz, a lentivirus closely related to HIV-1, in chimpanzees, and to obtain new SIVcpz isolates. METHODS: Forty-four wild-captured chimpanzees in Belgium and Côte d'Ivoire were tested for HIV and SIV antibodies. Virus was isolated from the peripheral blood lymphocytes of positive animals and characterized by electron microscopy, Western blot and radioimmunoprecipitation assay. RESULTS: One animal had antibodies that cross-reacted with HIV-1. A lentivirus was isolated and referred to as SIVcpz-ant. With regard to molecular weight patterns, SIVcpz-ant differs from SIVcpz-gab' an HIV-1-related virus isolated from a wild-captured chimpanzee in Gabon. The major core protein, the transmembrane and outer membrane glycoproteins of the SIVcpz-ant strain consistently had higher molecular weights. Significantly more HIV-1-positive sera reacted with the envelope proteins of the Gabonese SIVcpz-gab strain than with the SIVcpz-ant strain. CONCLUSIONS: This study shows that natural infection of wild-captured chimpanzees with an HIV-related virus may not be uncommon. The diversity of the two chimpanzee isolates, the different geographical origin and the absence of disease suggest that chimpanzees have not recently become SIVcpz-infected.

Animals↗
PubMed1992

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.

ADP-ribosyl Cyclase↗
PubMed1992

Immunological comparison of HIV-1-, HIV-2- and dually-reactive women delivering in Abidjan, Côte d'Ivoire.

OBJECTIVES: To compare the basic immunological changes induced by HIV-1 and HIV-2 infection and to assess the immune status of subjects serologically reactive to both HIV-1 and HIV-2 (dually-reactive). DESIGN: Immune parameters were studied cross-sectionally in women delivering in Abidjan, Côte d'Ivoire, West Africa, where HIV-1 and HIV-2 are endemic. In this area, a significant number of sera from infected individuals are reactive to both HIV-1 and HIV-2. SUBJECTS AND METHODS: Two hundred and twenty-eight women delivering in a major maternity clinic were screened for HIV-1 and HIV-2 using an enzyme-linked immunosorbent assay. Seropositivity was confirmed by Western blot. The immune parameters studied were CD4+ and CD8+ lymphocyte subsets, immunoglobulin (Ig) serum levels, neopterin and beta 2-microglobulin (beta 2M) serum levels. RESULTS: Similar but less pronounced immune changes were present in HIV-2-reactive subjects compared with HIV-1- and dually-reactive subjects. The observed differences between the HIV-seropositive groups could not be explained by differences in age or disease stage but paralleled differences in the frequency of persistent generalized lymphadenopathy (PGL). The intermediate immune profile of HIV-2-reactives (between seronegatives and HIV-1- and dually-reactives) was most clearly reflected by the number of CD8+ lymphocytes, the CD4:CD8 ratio and the IgG serum level. Median neopterin and beta 2M levels, though significantly increased in all HIV-seropositive groups, did not differ significantly between HIV-2-, HIV-1- and dually-reactives. CONCLUSIONS: HIV-2 infection is associated with typical HIV-related immunological changes. Immunologically, dually-reactives resemble HIV-1-reactives more closely than HIV-2-reactive subjects.

Adult↗