Biomedical subjects

L Ginaldi

Publications and source records attributed to L Ginaldi.

At least 19 recordsLinked to original sources

PubMed2001

Changes in the expression of surface receptors on lymphocyte subsets in the elderly: quantitative flow cytometric analysis.

The immunophenotype of circulating lymphocytes, including the intensity expression of surface receptors, changes with ageing. Until now, no results of systematic studies on age-dependent changes with respect to the expression of the major lymphocyte surface receptors in healthy elderly subjects have been reported. In order to identify age-related changes in both representation and immunophenotype of lymphocyte populations, we investigated, by means of triple-color whole-blood immunostaining and quantitative flow cytometry, the percent values and the absolute numbers, as well as the levels of surface antigen expression or antigen molecules per cell (ABC values x 10(3)), of different peripheral blood lymphocyte subsets from 23 healthy elderly subjects and 13 young donors. Naive (CD45RA+CD3+) T cells, total B cells, and CD5+ B lymphocytes are decreased (22%, 6%, 0.8% vs. 30%, 12%, 1.4%, respectively), whereas activated (HLA-DR+CD3+) and memory (CD45RO+CD3+) T cells, CD3+CD7- T lymphocytes, and lymphocytes expressing the NK marker CD56 are expanded in the elderly (2%, 53%, 13%, 6% vs. 0.8%, 45%, 8%, 8%, respectively). Moreover, T lymphocytes from elderly individuals express lower CD3 (61 +/- 10) compared to young (69 +/- 10). Considering the different T-cell populations, CD3 antigen is respectively decreased on CD45RO+ T cells (55 +/- 14 vs. 66 +/- 14) and up-regulated on CD56+ T lymphocytes (62 +/- 21 vs. 45 +/- 20). Increased CD8 expression characterizes CD3+CD7- lymphocytes (70 +/- 34 vs. 44 +/- 17) while HLA-DR on activated T cells is lower in old (39 +/- 7) than young (46 +/- 9) donors. CD7 is down-regulated both in T (22 +/- 3 vs. 28 +/- 3) and NK (48 +/- 18 vs. 71 +/- 18) cells, whereas CD2 expression, unchanged on NK cells, is up-regulated on T lymphocytes (54 +/- 10 vs. 41 +/- 8). Age-related changes in B-cell antigen expressions were also found: CD20 is increased (124 +/- 23 vs. 105 +/- 16) whereas, despite the unchanged CD5 expression of T cells, CD5 intensity on the B-cell subset co-expressing this antigen is higher in old (49 +/- 37) than in young (22 +/- 4) people. The observed changes in the expression of functionally important cellular receptors can contribute to the remodeling of immune function characteristic of the elderly. Moreover, since quantitative flow cytometry is becoming widely employed in clinical practice, our results also contribute to the assessment of specific age-dependent antigen expression changes to be considered for diagnostic approaches in the elderly.

Adult↗

PubMed2001

Immunosenescence and infectious diseases.

Infectious diseases are major causes, with malignancies, of morbidity and mortality in the elderly. Increased susceptibility to infections may result from underlying dysfunction of an aged immune system; moreover, inappropriate immunologic functions associated with aging can determine an insufficient response to vaccines. Impairments of cellular, humoral and innate immunity in the elderly, contributing to increased incidence of infectious diseases, are discussed in this review.

Aging↗

PubMed2000

Adhesion molecules on peripheral blood lymphocyte subpopulations in the elderly.

Adhesion molecules, such as CD49d, CD50 and CD62L, have important roles in many adhesive interactions involving cells of the immune system. Since it has been shown that many immunological alterations are present in aged subjects, we studied, by means of triple colour whole blood immunostaining and multiparametric flow cytometry, the expression and intensity level (MFI) of these molecules on peripheral blood lymphocyte subpopulations from 23 healthy elderly subjects and 13 young controls. In the elderly a decrease in total peripheral blood lymphocytes bearing CD62L antigen was observed (39 +/- 13% vs 63 +/- 6% and 745 +/- 312/mm3 vs 1,393 +/- 407/mm3; p<0.001), whereas the numbers of lymphocytes expressing CD49d and CD50 antigens were comparable in aged and young subjects. In addition, CD50 and CD62L MFI values on total peripheral blood lymphocytes were higher in elderly than in young subjects (5.23 +/- 1.03 vs 4.18 +/- 0.44, p = 0.001 and 2.60 +/- 0.35 vs 2.21 +/- 0.40, p = 0.005 respectively) while the intensity expression of CD49d was unchanged. The percentages and absolute numbers of T and B lymphocytes expressing CD62L were decreased in elderly compared to young subjects (CD62L+CD3+: 43 +/- 15% vs 66 +/- 9% and 581 +/- 257/mm3 vs 1,028 +/- 418/mm3, p<0.001; CD62L+CD19+: 78 +/- 12% vs 90 +/- 4%, p < 0.005 and 103 +/- 64/mm3 vs 207 +/- 98, p < 0.001). A decrease in the proportion of CD62L bearing NK cells was also observed in the elderly (25 +/- 14% vs 46 +/- 24%, p<0.005), although their absolute number was unchanged. No significant differences were detected in the proportion of T, B and NK lymphocytes expressing CD49d and CD50 antigens and only the absolute numbers of B cells expressing these adhesion molecules were lower in elderly (CD49d+CD19+: 121 +/- 71/mm3 and CD50+CD19+: 107 +/- 73/mm3) compared to young donors (CD49d+CD19+: 248 +/- 112/mm3 and CD50+CD19+: 235 +/- 120/mm3, p < 0.001). Moreover, the intensity of adhesion molecule expression was differentially modulated in the elderly depending on the specific lymphocyte cell population considered. The densities of CD49d, CD50 and CD62L antigens on B and NK lymphocytes from the two age groups were not different; on the contrary, T lymphocytes from elderly donors exhibited increased CD49d (1.69 +/- 0.09 vs 1.62 +/- 0.07, p < 0.05), CD50 (4.98 +/- 1.16 vs 3.77 +/- 0.46, p < 0.001) and CD62L (2.26 +/- 0.38 vs 1.99 +/- 0.37, p < 0.05) MFI values compared to young donors.

Adult↗

PubMed2000

Coagulation and cancer: implications for diagnosis and management.

Coagulation disorders are a common problem in neoplastic patients and many factors contribute to increase the risk of thromboembolic events in these patients. An hypercoagulable state is induced by malignant cells interacting directly with hemostatic system and activating the coagulation cascade. More sensitive tests to assess an hypercoagulable state in cancer patients have been developed; even though these tests are always altered in cancer patients, none of them possess a clinical significance in terms of predictive value for the occurence of thromboembolism and disease prognosis in the individual patient. The most frequent thromboembolic complications in cancer patients are deep vein thrombosis of the lower extremities and pulmonary embolism; therefore, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura or haemolytic uremic syndrome are special manifestations of neoplastic disease. Diagnosis of idiopathic deep vein thrombosis, in the absence of other risk factors, could indicate the presence of occult malignant disease; however, the need for an extensive work-up to detect malignancy is still controversial. Neoplastic patients showing a thromboembolic event should be treated with unfractioned heparin or, alternatively, with low molecular weight heparins. In order to prevent recurrence, the administration of heparin should be associated and followed by an oral anticoagulant drug. In recent years new approaches in anti-aggregation therapy have been studied, such as COX-inhibitors, cicaprost and ReoPro; further studies are needed to determine the usefulness of these molecules in treatment of malignancies.

Antineoplastic Agents↗

PubMed2000

CD50 and CD62L adhesion receptor expression on naive (CD45RA+) and memory (CD45RO+) T lymphocytes in the elderly.

A complex reshaping characterizes cellular immunity in the elderly. In particular, the hallmark of the "senescence" of the T cell compartment is a decrease in the proportion of CD45RA+ naive T lymphocytes concomitantly with an expansion of CD45RO+ memory T cells. However, in addition to age-dependent changes in their representation, phenotypical and functional anomalies also characterize naive and memory T cell populations in the elderly. Since cell adhesion molecules (CAMs) are multifunctional receptors which play important roles not only in cell-to-cell and cell-to-matrix interactions but also in signal transduction and cell activation, we analysed, by means of a three-colour flow cytometry method, the proportion, absolute number and density expression or mean fluorescence intensity (MFI) of CD50 (ICAM-3) and CD62L (L-selectin homing receptor) adhesion receptors on CD45RA+ and CD45RO+ peripheral blood CD3+ T cell subsets from 10 healthy elderly subjects and 10 young controls. Our aim was to investigate age-dependent changes in the expression pattern of these CAMs on naive and memory lymphocytes which might contribute to the remodelling of the immune system in the elderly. We considered the mean values +/- standard deviations of the percentage, absolute number and MFI of positive cells. The percentage of naive T cells expressing CD50 was not significantly modified in aged (94.8 +/- 5.0%) compared to young individuals (97.8 +/- 3.2%). On the contrary, the percentage of memory T cells exhibiting CD50 was lower in elderly than young donors (92.0 +/- 6.4 vs. 98.3 +/- 2.2%; p < 0.01). The percentage of naive T cells expressing CD62L was decreased in the elderly donors (53.3 +/- 18.8 vs. 80.8 +/- 11.0%; p < 0.001), whereas the proportion of CD62L+ memory T lymphocytes was substantially comparable between the two age groups (63.5 +/- 15.7 vs. 54.7 +/- 12.3%). The absolute number per mm(3) of CD50+ naive T cells from aged individuals was decreased (251.9 +/- 141.9 vs. 621.8 +/- 238.0/mm(3); p < 0.001), whereas memory peripheral blood T lymphocytes expressing CD50 were substantially unchanged (863.8 +/- 260.9 vs. 802.7 +/- 139.6/mm(3)). On the contrary, the absolute numbers per mm(3) of naive and memory peripheral blood T lymphocytes exhibiting CD62L were respectively decreased (190.8 +/- 133.4/mm(3)) and increased (515.1 +/- 146.8/mm(3)) in elderly donors compared to young controls (601.3 +/- 129.1 and 351.8 +/- 195.0/mm(3); p < 0.001 and p < 0.05, respectively). Finally, CD50 MFI values of naive as well as memory T cell subpopulations from aged subjects were increased compared to young donors (14.0 +/- 2.0 vs. 9.8 +/- 1.2 and 14.0 +/- 2.0 vs. 11.6 +/- 1.3; p < 0.001 and p < 0.01, respectively). CD62L was also overexpressed in both naive (8.4 +/- 1.6 vs. 6.7 +/- 1.4; p < 0.05) and memory (10.3 +/- 2.5 vs. 5.4 +/- 1.1; p < 0.001) T subsets in the elderly. CD50 and CD62L upregulation could be interpreted as a compensatory mechanism for a decreased responsiveness and a greater requirement for activation signals rather than an age-related anomaly.

Adult↗

PubMed2000

Cell proliferation and apoptosis in the immune system in the elderly.

Loss of the cell proliferative capability and involution of tissues and organs are among the most important phenomena that characterize the aging process. Some of the aged-linked immune dysfunctions could be partly due to a dysregulation of apoptotic processes and to a lower responsiveness of aged lymphoid cells to activation and proliferation signals. The main changes in proliferative activity and cell death during aging and their impact on the process of immunosenescence are discussed. In fact, a very important function that has been suggested to deteriorate with age and to play a major role in the aging process is the capability of cells from aged subjects to respond to mitogenic stimuli and, consequently, to undergo cell proliferation. However, the cellular activation processes are very complex and the proliferative responses can follow different interconnected signal transduction pathways, and only some of them appear to be modified during age. Moreover, cell growth, immunosenescence, and longevity are strictly interconnected and deeply related to programmed cell death or apoptosis. The cellular equilibrium between cell survival and proliferation, on the one hand, and programmed cell death, on the other hand, seems to be unbalanced with advancing age, although in each type of immune cell it could be differentially modulated, resulting in a variety of clinicopathological consequences. Thus, cell proliferation and cell death are two physiologically active phenomena closely linked and regulated and a failure of these mechanisms determines profound dysregulations of cell homeostasis with major consequences in immune functioning and the onset of autoimmune diseases and cancer, whose incidence appears to be increased in the elderly.

Aging↗

PubMed2000

[Extranodal localizations of lymphoma. Clinico-epidemiologic study of 353 cases].

The Authors have carried out a retrospective study on 353 cases of lymphoma, of which 252 of non-Hodgkin lymphoma (NHL) and 101 cases of Hodgkin's disease (HD), during a 17 year period, i.e. from 1982 to 1999, with the purpose of evaluating the frequency of primitive and secondary extra-nodal localizations and assess their influence on the percentage of survival. A highly significant statistical difference was observed comparing patients with nodal LNH and those with a primitive extra-nodal localization of the disease. In HD extra-nodal localizations were observed at the time of diagnosis in 13% of the cases studied, in which however in the great majority of patients presentation was associated with generalized disease and was therefore the consequence of local spread from near-by lymphoid sites. However, primitive localizations were surely observed and carefully documented. In our patients they were detected in the intestine, in the skin and in the mammary gland. In 253 patients with NHL, 123 sites of extranodal localizations were found (50%) and were observed in the skeletal system, in the skin and in the orbital cavity. The Authors underline the need to improve our knowledge on the structures and mechanisms of spread of the mucosal associated lymphoid tissue in order to better understand the clinical aspects and the necessary therapeutic approach in cases of extranodal and especially MALT lymphomas.

Adult↗

PubMed1999

The immune system in the elderly: I. Specific humoral immunity.

Profound and complex changes in the immune response occur during the aging process. Immunosenescence is reflected by a sum of disregulations of the immune system and its interaction with other systems. Many of the changes would appear to implicate age-related deficiencies of the immune responses. The term immunosenescence designates therefore a sort of deterioration of the immune function which is believed to manifest itself in the increased susceptibility to cancer, autoimmune disease, and infectious disease. Evidence has been accumulating from several studies which suggest an association between immune function and individual longevity. However, there are observations, especially in very old healthy people, that several immune functions are unexpectedly well preserved and substantially comparable to those observed in young subjects. These findings raise the question of whether the alterations that can be observed in the immune parameters of the elderly are a cause or a result of underlying disease processes. Moreover, studies on centenarians revealed a remodeling of the immune system rather than a deterioration, suggesting that the changes observed during immunosenescence do not correspond to immunodeficiency. The underlying mechanisms of these events are however still unclear. The purpose of the present review is to assess the status of research on the immunobiology of aging. In this first section, we focus attention on the B cell biology of aging. In clinical practice, the changes in humoral immune responsiveness and antibody-mediated defense mechanisms could greatly influence the incidence and outcome of bacterial infections and autoimmune diseases as well as the response to vaccines.

Aged↗

PubMed1999

The immune system in the elderly: II. Specific cellular immunity.

Numerous changes occur in the immune system with advancing age, probably contributing to the decreased immunoresponsiveness in the elderly. These changes are often associated with important clinical manifestations such as increased susceptibility to infection and cancer frequently observed in the elderly population. Although both cellular and humoral immune responses are modified with advancing age, much of the decrease in immunoresponsiveness seen in elderly populations is associated with changes in T cell responses. The loss of effective immune activity is largely due to alterations within the T cell compartment which occur, in part, as a result of thymic involution. Substantial changes in both the functional and phenotypic profiles of T cells have been reported with advancing age. In fact, two prominent features of immunosenescence are altered T cell phenotype and reduced T cell response. One of the most consistent changes noted in T cells with advancing age is the decrease in the proportion of naive T cells with a concomitant increase in T cells with an activated/memory phenotype. In addition, there is evidence that the T cell population from aged individuals is hyporesponsive. The observed functional changes include decreased responsiveness to T cell receptor stimulation, impaired T cell proliferative capacity, a decline in the frequency of CD4+ T cells producing IL-2 and a decreased expression in IL-2 receptors. These latter findings probably explain the loss of proliferative capability of T cells from aged individuals. There is also evidence of a decrease in the early events of signal transduction, decreased activation-induced intracellular phosphorylation, and decreased cellular proliferative response to T cell receptor stimulation. The present review analyzes the main changes of the T cell compartment characterizing immunosenescence and discusses the possible mechanisms underlying these disregulations and their clinical implications.

Aged↗

PubMed1999

The immune system in the elderly: III. Innate immunity.

The capability to cope with infectious agents and cancer cells resides not only in adaptive immune responses against specific antigens, mediated by T and B lymphocytes clonally distributed, but also in natural immune reactions. These innate defence mechanisms include chemotaxis, phagocytosis, natural cytotoxicity, cell interactions, and soluble mediators or cytokines. However, specific and natural immune mechanisms are always closely linked and interconnected, providing the primary defense against pathogens. The Authors discuss the main changes observed with advancing age in granulocytes and natural killer (NK) cell activity, in the expression and function of adhesion molecules, and in the pattern of cytokine production. Since phagocytic function is the primary mechanism through which the immune system eliminates most extracellular pathogenic microorganisms, analysis of this function is of clinical importance. Neutrophils from aged subjects often exhibit a diminished phagocytic capacity, as well as a depressed respiratory burst, notwithstanding an activated state. The activity of NK cells during aging has been studied extensively and different results have been reported. The most consistent data indicate an increase in cells with high NK activity with advancing age. Cells from healthy centenarians can efficiently kill target cells. This finding seems to suggest that innate immunity and in particular NK cell activity, is not heavily deteriorated with age. Conversely, a low NK activity is a predictor of impending morbidity. Immunosenescence is associated with increased expression of several cell adhesion molecules (CAM) resulting in an augmented capacity to adhere. Finally, also the cytokine network, responsible for differentiation, proliferation, and survival of lymphoid cells, undergoes complex changes with age. The main findings are a Th1 to Th2 cytokine production shift and an increased production of proinflammatory cytokines, which could explain many aspects of age-associated pathological events, such as atherosclerosis and osteoporosis.

Aged↗

PubMed1999

Immunological changes in the elderly.

Immunosenescence is a complex remodelling of the immune system which may contribute significantly to morbidity and mortality in the elderly. Much evidence suggests an association between immune function and longevity. It was advanced that individuals who have survived in good health to the maximum life span are equipped with optimal cell defense mechanisms. Despite the great number of studies on the immune system in the elderly, little is known of the biological basis of immunosenescence in humans. This is partly due to the contrasting results often obtained by the various investigators. One source of discrepancy is that diseases are frequent in aging, and the alterations observed in the immune parameters of the elderly could be a cause or alternatively a consequence of the underlying pathological processes. Undoubtedly some diseases to which aged people are particularly susceptible, such as infectious, autoimmune and neoplastic pathologies, include dysregulation of several immune functions in their pathogenesis. On the other hand, recent studies in healthy centenarians suggest that the immunological changes observed during aging are consistent with a reshaping, rather than a generalized deterioration, of the main immune functions. Considering that the number of old people is dramatically increasing, and that geriatric pathology is becoming an important aspect of clinical practice, it seems particularly interesting to review the peculiar findings in the immune system of the elderly so as to better understand their susceptibility to certain diseases, and the links between health and longevity.

Aging↗

PubMed1998

Proliferating cell nuclear antigen expression is increased in small bowel epithelium in the elderly.

Although previous studies suggest that in aging animals the small intestine is in a hyperproliferative state, no information is currently available on the influence of age on the proliferation pattern of human small bowel enterocytes. The immunohistochemical expression of the proliferating cell nuclear antigen (PCNA), the villous height to total mucosal thickness ratio and the enterocyte height were evaluated in a panel of duodenal biopsy specimens obtained from 18 subjects aged less and 14 subjects aged more than 65 years. There was a significant positive correlation (P < 0.001) between age in years and percent of positive PCNA enterocytes both at the level of crypts (rs = 0.50) and villi (rs = 0.77). Moreover, the percentage of PCNA+ enterocytes was significantly higher in elderly versus adult subjects, both at the level of villi (6.5 vs 0%; P < 0.001) and of crypts (40.0 vs 23.7%; P < 0.01). No correlation was found between the percentage of PCNA + enterocytes and enterocyte height or villous height to total mucosal thickness ratio. Our results show that PCNA reactivity increases with advancing age both in crypts and villi. This abnormality of the proliferation pattern may explain the coexistence of normal morphology and impaired absorptive function in the elderly.

Adult↗

PubMed1998

Levels of expression of CD52 in normal and leukemic B and T cells: correlation with in vivo therapeutic responses to Campath-1H.

The CD52 antigen is expressed on most normal and neoplastic lymphoid cells. The reshaped humanized IgG1 anti-CD52 monoclonal antibody (Campath-1H) has been used in the treatment of hemopoietic and non-hemopoietic diseases for its ability to induce lymphocyte depletion both in vitro and in vivo. Good activity has been shown in patients with chronic T and B cell leukemias, in particular T-prolymphocytic leukemia (T-PLL). However, the response to treatment is not uniform and this variability may depend on differences in the level of antigen expression on the leukemic cells. To test this hypothesis, we used quantitative flow cytometry to investigate the intensity of the expression of CD52 in 45 cases of lymphoid leukemia, 24 with B-cell chronic lymphocytic leukemia (CLL), 21 with T-PLL and 12 normal controls. Normal T lymphocytes expressed higher CD52 antigen than B lymphocytes (p < 0.005) and the antigen was also significantly higher in T-PLL compared to CLL (p < 0.001). Moreover, the differences in CD52 expression were somewhat higher in Campath-1H treated patients who responded than in non responders. Although other factors may play a role in the response to Campath-1H in vivo, the quantitative estimation of CD52 expression may provide a rationale for the greater response in T-PLL and help select those patients with a higher probability of responding to this therapy.

Alemtuzumab↗

PubMed1998

Levels of expression of CD19 and CD20 in chronic B cell leukaemias.

AIMS: To investigate whether the antigen levels of the B cell lineage markers CD19 and CD20 can distinguish between normal and neoplastic B cells or characterise distinct expression patterns among the chronic B cell leukaemias. METHODS: Peripheral blood cells from 70 patients with B cell disorders and 17 healthy donors were analysed by quantitative flow cytometry. Direct immunofluorescence staining was performed with phycoerythrin conjugated CD19 and CD20 monoclonal antibodies. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity (MFI) values into number of antigen molecules/cell, expressed as antibody binding capacity (ABC). RESULTS: CD19 and CD20 ABC values in leukaemic B cells differed from those of normal blood B lymphocytes. The results identified distinct profiles of CD19 and CD20 expression in the various types of B cell leukaemias. In all leukaemias studied except hairy cell leukaemia (HCL), CD19 expression was significantly lower than the mean (SD) value in normal B cells (22 (7) x 10(3) molecules/cell), as follows: chronic lymphocytic leukaemia (CLL), 13 (7) x 10(3); B prolymphocytic leukaemia (B-PLL), 16 (9) x 10(3); splenic lymphoma with villous lymphocytes (SLVL), 15 (11) x 10(3); mantle cell lymphoma (MCL), 10 (7) x 10(3). In HCL there was strong CD19 expression (38 (16) x 10(3)). In contrast, the level of expression of membrane CD20 was higher than the mean (SD) value in normal B cells (94 (16) x 10(3) molecules/cell) in MCL (123 (51) x 10(3)); B-PLL (129 (47) x 10(3)); SLVL (167 (72) x 10(3)); and HCL (312 (110) x 10(3)); while it was significantly lower (65 (11) x 10(3)) in CLL compared with normal B cells and the other B cell leukaemias. CONCLUSIONS: Quantitative determination of CD19 and CD20 may provide useful diagnostic information for the study of B lymphoproliferative disorders.

Antigens, CD19↗

PubMed1998

Changes in antigen expression on B lymphocytes during HIV infection.

Involvement of the B cell compartment during HIV infection plays an important role in the development of immune deficiency. The aim of this study was the identification of specific antigen expression changes on B lymphocytes in HIV infection as surrogate markers in this cell population of certain functional aspects that could be easily measured. We investigated the level of expression of a series of constitutive surface markers in B lymphocytes (HLA-DR, CD19, CD20, CD21, CD22) from 30 HIV-seropositive adult patients and 20 normal controls. By means of quantitative flow cytometry, we assessed the number of antigen molecules per cell using standard beads to convert fluorescence intensity into antibody-binding capacity (ABC). We correlated these results with disease stage and cellular markers of immune activation. The expression of CD20 was significantly increased when B cells from HIV-infected individuals were compared with those from uninfected subjects. No differences were found in the density expression of HLA-DR on activated CD3+ T cells between HIV+ and HIV- subjects. In contrast, B cells from HIV+ patients showed a significantly lower number of HLA-DR molecules per cell compared to normal controls. A significantly lower number of CD21 molecules per cell was also found on B lymphocytes from HIV+ patients compared to normal controls. No differences in CD19 and CD22 expression levels on B cells between HIV-infected patients and controls were detected. No differences between HIV disease stages were detected for CD19, HLA-DR, CD21 and CD22. In contrast, differences between stages were found for CD20 expression, which showed significant changes in individuals with less than 200 CD4 T cells/microl. The data presented here demonstrate that B lymphocytes of HIV-infected individuals exhibit specific changes in receptor density expression during HIV infection and that these changes are often correlated with progression of disease, as measured by CD4 counts. No correlations were found between the percentages of HLA-DR+ T cells and the ABC values of the B cell markers studied. These antigen expression modulations may contribute to the humoral abnormalities during HIV infection and to the development of severe, recurrent or multiple bacterial infections. Therefore, quantitative flow cytometry may be of value in HIV infection both for clinical and biological studies. The study of antigen density changes on B cells in HIV infection may allow a better understanding of the humoral immune defects observed in these patients and provide insights into the functional defects of B cell compartment in HIV-infected individuals.

Adult↗

PubMed1997

The impact of HIV infection on lactose absorptive capacity.

Forty HIV-infected adult patients at different disease stages and 44 healthy volunteers were evaluated for lactose malabsorption using the hydrogen breath test after 20 g lactose ingestion. All subjects were previously tested for breath hydrogen (H2) excretion after 12 g lactulose ingestion. The presence of intestinal superinfections, gastrointestinal symptoms and the intensity of clinical intolerance after lactose load were accurately searched in each patient. The cumulative H2 excretion after lactulose did not significantly differ between the different groups studied. The prevalence of lactose malabsorption turned out to be significantly higher (P < 0.001) in HIV-infected patients (70%) than in controls (34%). Moreover, in patients in more advanced disease stages the degree of lactose malabsorption was significantly greater than in patients at earlier disease stages, who did not differ from healthy volunteers. Furthermore the degree of lactose intolerance was significantly greater (P < 0.001) in symptomatic patients than in those without intestinal symptoms and in healthy volunteers, while no significant difference was observed between these latter groups. The results here demonstrate the negative impact of HIV infection on lactose absorptive capacity in adult patients, particularly marked in more advanced stages of the disease, suggesting that, in addition to the presence of the virus alone, other factors may contribute to determine the enterokinetic alterations responsible for lactase deficiency.

Adolescent↗

PubMed1997

Altered lymphocyte antigen expressions in HIV infection: a study by quantitative flow cytometry.

To identify surface antigen changes that may contribute to the immune deficiency in infection with the human immunodeficiency virus (HIV), we quantified, by double-staining flow cytometry, the number of antigens of the main peripheral blood lymphocyte subsets from 30 HIV-positive persons and compared them with those of 19 HIV-negative healthy donors. Standard microbeads with different capacities to bind mouse immunoglobulins were used to convert the mean fluorescence intensity values into numbers of antigen molecules per cell, measured as antibody binding capacity. The level of expression of different lymphocyte antigens in HIV-infected patients differs from that seen in normal blood lymphocytes. Some of these surface markers are decreased, whereas others are increased, and their expression is modulated depending on the specific cell subset considered. The expression of CD3, CD4, and CD8 on T lymphocytes is significantly decreased; moreover, CD3 is down-regulated on activated and nonactivated T lymphocytes and on CD4 and CD8 cells. In contrast, the expression of CD2 on T cells is significantly increased. Natural killer cells exhibit down-regulation of CD7, normal levels of CD8 and CD56, and overexpression of CD2. Our results also identified, for most of these antigens, quantitative differences in membrane expression according to different disease stages, as assessed by the CD4 T-cell count. Quantitative flow cytometry therefore may provide useful insights into the lymphocyte functional defects characterizing HIV infection.

Adult↗

PubMed1997

Activated naive and memory CD4+ and CD8+ subsets in different stages of HIV infection.

The aim of this study was to evaluate the changes and the correlations between the main lymphoid phenotypes indicative of activation and/or functional states during the course of HIV infection. Immunophenotype studies by flow cytometry were performed on blood samples from 59 HIV-1-positive patients, divided into four stages, and 18 seronegative healthy controls, to determine the expression of HLA-DR, CD29 and CD45RA on CD4+ and CD8+ lymphocytes. HLA-DR expression was elevated on the total lymphocyte population and in both the main T subsets. Its presence on CD4+ lymphocytes probably has a different significance in the first phase of infection when it is indicative of reactive activation, in contrast to the more advanced stages of disease when it favors the spread of HIV infection among this cellular subset. The increasing state of immune activation is also confirmed by a proportional decrease in the expression of CD45RA, substantial stability of CD29 and an increase in double-negative CD4+ cells as the infection proceeds. Also CD8+HLA-DR+ lymphocytes increase during the course of disease. The parallel increase of the CD8+CD45RA+ subset in asymptomatic patients suggests the presence in this phase of infection of peripheral blood immature and activated CD8+ cells. Similarly to CD4+, the CD29 subset of CD8+ lymphocytes remains unchanged compared to controls during disease progression. In both CD4+ and CD8+ subsets we observed the increase of a double-negative sub-population of uncertain significance. HLA-DR, the memory marker CD29 and the naive marker CD45RA seem to be the more promising and helpful indicators for a better staging of disease and may provide information that accurately correlates with progression of infection. The peculiar trend of the described phenotypic alterations could represent changes in the immune response to HIV during disease progression and facilitate the definition of specific immune patterns in different stages of HIV infection.

Adult↗