Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The ability of an alpha CD4-pokeweed antiviral protein (PAP) immunoconjugate to inhibit replication of human immunodeficiency virus type 1 (HIV-1) was evaluated in vitro with 22 clinical HIV-1 strains obtained from four seropositive asymptomatic individuals, three patients with AIDS-related complex, and four patients with AIDS. Fifteen isolates were from zidovudine-untreated individuals, whereas seven isolates were obtained after 24 to 104 weeks of therapy with zidovudine, alone or alternating with zalcitabine. Mean zidovudine 50% inhibitory concentrations (IC50s) were 126 nM (range, 1 to 607 nM) for isolates from zidovudine-untreated individuals and 2,498 nM (range, 14 to 6,497 nM) for strains from patients treated with antiretroviral agents. Mean alpha CD4-PAP IC50s were 48 x 10(-3) nM (range, 0.02 x 10(-3) to 212 x 10(-3) nM) for isolates from zidovudine-untreated individuals, and 16 x 10(-3) nM (range, 2 x 10(-3) to 28 x 10(-3) nM) for isolates from treated patients. Overall, higher concentrations of alpha CD4-PAP were necessary to inhibit HIV-1 strains from untreated individuals at more advanced stages of disease. Seventeen isolates were susceptible to zidovudine (mean IC50, 117 nM), and five were resistant to zidovudine (mean IC50, 3,724 nM). Mean alpha CD4-PAP IC50s were 43 x 10(-3) nM for zidovudine-susceptible isolates and 19 x 10(-3) nM for isolates resistant to zidovudine. All HIV-1 strains had IC50s greater than 0.5 nM for unconjugated PAP, the alpha CD19-PAP immunoconjugate, and monoclonal antibody alpha CD4. At concentrations as high as 5,000 nM, alphaCD4-PAP did not inhibit colony formation by normal bone marrow progenitor cells(BFU-E, CFU-GM , and CFU-GEMM) or myeloid cell lines (KG-1 and HL-60) and did not decrease cell viabilities of T-cell (Jurkat) or B-cell (FL-112 and Raji) precursor lines. Overall, alphaCD4-PAP demonstrated more potent anti-HIV-1 activity than zidovudine and inhibited replication of zidovudine-susceptible and zidovudine-resistant viruses at concentrations that were not toxic to lymphohematopoietic cell populations.
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PMID:Anti-human immunodeficiency virus type 1 activity of an anti-CD4 immunoconjugate containing pokeweed antiviral protein. 849 81

The immunostimulatory activity of a phosphorothioate oligodeoxynucleotide (27 mer) that is antisense to the rev gene of HIV-1 was studied on normal human lymphocytes and on cells from patients with common variable immunodeficiency (CVI). For peripheral blood mononuclear cells from nine normal individuals, the proliferation index (16.8 +/- 12.5) after anti-rev oligomer exposure was proportional to the percentage of peripheral B-cells (r = 0.76, P = 0.02). In five experiments, enriched B- or T-cell populations had proliferation indices of 47.2 +/- 32.9 and 2.4 +/- 1.9, respectively. The addition of T-cells to anti-rev oligomer treated B-cells had no effect (proliferation index = 47.5 +/- 38.1). After anti-rev oligomer stimulation, autoradiography, and counterstaining for B- and T-cell markers, all detectable [3H]thymidine uptake was by CD19-positive cells. Eight of the 14 CVI patients had a proliferation index and secreted levels of IgM and IgG comparable to cells from normal individuals. In contrast to normal cells, the direct correlation between proliferation of peripheral blood mononuclear cells and the percentage of peripheral B-cells was weak in samples from 13 CVI patients (r = 0.4, P = 0.2). These findings indicate that peripheral blood B-cells from about half of CVI patients proliferate and produce immunoglobulin after exposure to anti-rev oligomer. These data demonstrate that under the appropriate circumstances, B-cells of some CVI patients can proliferate and differentiate normally.
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PMID:B-cell proliferation and differentiation in common variable immunodeficiency patients produced by an antisense oligomer to the rev gene of HIV-1. 862 Jun 17

Despite the relatively early reconstitution of blood B-lymphocyte counts observed in patients treated with bone marrow transplantation (BMT), these patients undergo a prolonged phase of humoral immunodeficiency. Adhesion molecules perform relevant functions in many cell types. The present study examines the expression of several adhesion molecules on human B lymphocytes newly formed after BMT. Blood B cells from 38 patients were studied by flow cytometry and three-color analysis. Blood CD5- B lymphocytes obtained at an early stage after BMT (2 to 4 months) showed a markedly low expression of the adhesion molecules CD54, CD44, CD11a, and CD62L. However, these cells exhibited a normal expression of other molecules including CD29, CD19, CD20, and DR. This deficiency was progressively corrected, reaching normal levels in the late post-BMT period (12 to 15 months). In contrast, CD54, CD44, CD11a, and CD62L expression on the patients' CD5+ B lymphocytes was found to be consistently normal. Deficient adhesion molecule expression on CD5- B cells in the early post-BMT period was similarly observed in patients treated with either an allo-BMT (n = 24) or an auto-BMT (n = 14). Because the post-BMT period mimics normal ontogeny, adhesion molecule expression was also investigated in cord-blood B lymphocytes. Cord-blood CD5- B lymphocytes, in contrast to CD5+, also expressed CD54, CD44, CD11a, and CD62L at levels much lower than those found in normal adults. Present data suggest that progressive expression of CD54, CD44, CD11a, and CD62L seems to be a part of the maturational program of CD5- B lymphocytes during both post-BMT and normal development periods. This observation may help to explain the humoral immunodeficiency observed in both conditions.
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PMID:Deficient expression of adhesion molecules by human CD5- B lymphocytes both after bone marrow transplantation and during normal ontogeny. 878 29

A cross-sectional study on the expression of 6 lymphocyte markers was carried out on 481 patients with human immunodeficiency virus (HIV) and 79 normals after stratification based on absolute CD4 counts. The data were stratified according to the following groups: (I) 1201 to 1600, (II) 801 to 1200, (III) 401 to 800 and (IV) 0 to 400 (x 10(6) CD4 cells per mm3). The mean percentages of the subsets before stratification showed that HIV patients had increased percentages of CD3+ (75.7 against 66.9), CD3+CD8+ (52.2 against 32.3) and CD3+HLA-DR+ (36.1 against 14.4) cells and lower percentages of CD19 (10.3 against 13.3) and natural killer cells (13.7 against 20.4) when compared to controls in the same group. A definite trend, however, was only seen in CD3+CD8+ (47.4, 50.0, 54.0, 57.5 for groups I, II, III and IV respectively) and CD3+HLA-DR+ (29.1, 32.9, 38.4, 43.9 for groups I, II, III and IV respectively).
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PMID:Significantly increased activated T cells are associated with declining CD4 cells in human immunodeficiency virus positive patients. 883 81

In the present study the phenotype and function of lymphocytes from patients with common variable immunodeficiency (CVI) were studied. Five out of 12 patients had abnormally low proportion of CD4+ T cells, but PBMC of these patients were capable of proliferating in response to polyclonal T-cell mitogens or PPD antigen. The phenotype of patients' B cells, as determined by expression of CD10, CD19 and CD34, was comparable to that of healthy controls. IL-4 and anti-CD40 MoAbs induced moderate B-cell differentiation in PBMC derived from patients with CVI, but the frequencies of Ig-secreting cells were generally at levels spontaneously observed in healthy controls. IL-10 was completely ineffective in inducing IgG-secreting cells in cultures of PBMC derived from patients with CVI even in the presence of anti-CD40 MoAbs, whereas high frequencies of Ig-secreting cells were induced under similar condition in cultures of PBMC derived from healthy controls. Importantly, when IL-4 was added to cultures stimulated with anti-CD40 MoAbs and IL-10, a very strong synergistic effect on the numbers of Ig-secreting cells and the levels of Ig secretion was observed in PBMC from both patients and controls. Moreover, the frequencies of Ig-secreting cells after activation with anti-CD40 MoAbs, IL-4 plus IL-10 in PBMC from some patients were comparable to those observed in PBMC from healthy controls. Taken together, these results indicate that B cells from patients with CVI have impaired capacity to differentiate into Ig-secreting cells in response to IL-10 and anti-CD40 MoAbs, and that this unresponsiveness can be restored by exogenous IL-4 in a proportion of the patients.
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PMID:IL-4 synergizes with IL-10 and anti-CD40 MoAbs to induce B-cell differentiation in patients with common variable immunodeficiency. 904 33

To clarify the interrelations among drug abuse, malnutrition, and immunosuppression, the effects of human immunodeficiency virus (HIV) infection on the nutritional status of 17 noninfected and 19 HIV-infected asymptomatic female drug addicts undergoing detoxification were evaluated by measuring anthropometric and immunologic indexes. Anthropometric measurements were normal in both groups as a result of weight gain (approximately 10 kg) in every patient after the detoxification period. Leukocyte and lymphocyte values and CD2 lymphocyte subset counts were also similar in both groups. CD4 counts (P = 0.04) and the ratio of CD4 to CD8 cells (P = 0.6 x 10(-4)) were lower whereas CD8 counts (P = 0.003) were higher in the HIV-infected than in the noninfected group. Responses to a delayed-hypersensitivity skin test were below normal in both groups but significantly more so in the HIV-positive group (P = 0.05). CD19 counts were lower (P = 0.02) and values for serum immunoglobulins G and M were higher (51% and 37%, respectively) in the HIV-infected females than in the noninfected women. These results may suggest that despite anthropometric recovery, the HIV-infected women had depleted immune function, resulting not only from HIV infection but also from the subclinical malnutrition triggered by previous drug addiction.
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PMID:Human immunodeficiency virus infection and nutritional status in female drug addicts undergoing detoxification: anthropometric and immunologic assessments. 925 Jan 39

In mice, Pax5 gene is indispensable for B cell development. Pax5-deficient mice fail to produce mature B cells owing to complete arrest of B cell development at a precursor stage. However, the lineage and stage of human Pax5 gene expression have remained elusive. In this investigation expression of the human Pax5 gene was studied. Pax5 gene expression was detected in B cell lines but not in myeloma cell lines. CD19 expression was correlated with Pax5 gene expression. Adult spleen and bone marrow and fetal spleen and liver showed strong Pax5 gene expression, as did the corresponding mouse tissues, as reported previously. In common variable immunodeficiency (CVID) peripheral blood lymphocytes (PBL) with a decreased number of B cells, no Pax5 gene expression was detected. Some CVID PBL stimulated with IL-2, IL-10 and anti-CD40 monoclonal antibody, expressed the Pax5 gene. Defect of Pax5 gene expression in CVID may be caused by regulatory T cell disorder.
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PMID:Expression of Pax5 gene in human haematopoietic cells and tissues: comparison with immunodeficient donors. 948 1

We investigated the presence of human T-lymphotropic virus type 2 (HTLV-2) DNA in the peripheral blood mononuclear cell subsets obtained from 18 patients coinfected with human immunodeficiency virus type 1 and HTLV-2, 6 of whom also had predominantly sensory polyneuropathy (PSP). HTLV-2 DNA and RNA were found in CD8- and CD19-positive cells, and, for patients with PSP, in CD14-positive cells as well. Furthermore, the patients with PSP had higher proviral loads than those without PSP.
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PMID:Human T-lymphotropic virus type 2 (HTLV-2) provirus in circulating cells of the monocyte/macrophage lineage in patients dually infected with human immunodeficiency virus type 1 and HTLV-2 and having predominantly sensory polyneuropathy. 969 72

The phenotypic analysis of human umbilical cord blood (CB) mononuclear cells is important to study their maturity and differentiation regarding their transplantable capacity. In this work we have studied differential expression of B cell antigens on CD5-/HLA-DR+ B cells (B1b, B2) and CD5+/HLA-DR+ cells (Bla) from the CB (n=6) and adult peripheral blood (PB) (N=6). CD5-PE, HLA-DR-PerCP and FITC labelled anti-B cell MoAb panel of the 6th International Workshop on Human Differentiation Antigens were used for detection of B cell subpopulations. FacsCalibur (B-D) flow cytometer was used for evaluation of samples. CB Bla (CD5/HLA-DR++) cells proved to be positive with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD76, CD79, MHC-II, IgM and anti Ig light chains MoAbs. CB B1b (CD5-/HLA-DR+) cells reacted with CD9, CD19, CD20, CD21, CD22, CD23, CD24, CD32, CD39, CD45RA, CD79, MHC-II, and IgM MoAbs. PB B cells (B2) expressed CD19, CD20, CD21, CD22, CD24, CD32, CD37, CD39, MHC-II and CD79 Ags. Unlike to the PB the CB B lymphocytes proved to be predominantly B1 cells representing a new-born B cell repertoire. Besides expressing many B cell antigens both the CB Bla and B1b cells showed CD9+, CD45RA+, IgM+ immature, "naive" B cell phenotype. Functionally, B1 cells are capable producing polyreactive IgM and natural autoantibodies but not IgG. This antibody profile might be insufficient regarding the recipient humoral immune defense result in more severe immunodeficiency after CB transplantation.
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PMID:Immunophenotypic characterisation of cord blood B-lymphocytes. 991 47

Regeneration and tolerance factor (RTF) plays a pivotal role in successful pregnancy outcome and has potent immunomodulating properties. During pregnancy, it is abundantly expressed in the placenta and on peripheral B lymphocytes. Several lines of evidence suggest that both successful pregnancy outcome and progression from human immunodeficiency virus (HIV) infection to AIDS are associated with a Th2-type response. As a result, we hypothesized that the cellular expression of RTF may also be increased during infection with HIV. Using flow cytometric analysis, we showed a significantly (P < 0.01) increased expression of RTF on CD3(+) cells obtained from individuals with HIV over that for individuals without HIV. On average, 32.1% of the CD3(+) cells from individuals with HIV expressed high levels of RTF. In contrast, an average of only 6.7% of the CD3(+) cells from individuals without HIV expressed high levels of RTF. Similar results were obtained when CD19(+) cells from individuals with (mean, 44.1%) and without (mean, 25.8%) HIV were evaluated. Linear regression analysis suggested that high levels of RTF expression by CD3(+) cells correlated better with viral load (r value, 0.46) than with absolute CD4 count (r value, 0.09). While additional experiments are necessary to delineate the precise immunologic role of RTF, our current data suggest that RTF expression during HIV infection may be a useful marker of immune activation.
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PMID:Increased expression of regeneration and tolerance factor in individuals with human immunodeficiency virus infection. 1006 53


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