Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We report four cases of Omenn's syndrome (OS), an autosomal recessive disease characterized by early erythrodermia, protracted diarrhea, severe infections, lymphadenopathy, hepatosplenomegaly, failure to thrive, and leukocytosis with marked eosinophilia. The immunological investigations revealed B lymphopenia with increased levels of serum IgE and marked depression of T-cell activation, not restored by the addition of exogenous interleukin 2 (IL-2). IL-2 and interferon-gamma (IFN-gamma) production in vitro were very low or absent. One patient was treated with HLA-identical bone marrow transplant with a complete remission of the clinical picture and the immunological defect. The infant died of graft versus host disease 4 months after the graft. For the remaining three infants the outcome was also fatal within the first year of life. In conclusion, OS should be considered a severe combined immunodeficiency disease with peculiar clinical, immunological, and histological findings.
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PMID:Clinical and immunological findings in four infants with Omenn's syndrome: a form of severe combined immunodeficiency with phenotypically normal T cells, elevated IgE, and eosinophilia. 311 64

Twenty-two patients with refractory malignancies were treated with four escalating weekly doses of recombinant interleukin 2 (IL2), given either i.v. by 2- or 24-h infusion, or s.c. A 1-wk washout period between each dose of IL2 was provided for the evaluation for pharmacokinetic and immunomodulatory effects. The maximum i.v. dose was 30 X 10(6) units; the dose-limiting toxicities were fever, flu-like symptoms, and hypotension. The maximum s.c. dose was 3 X 10(6) because of volume limitations with s.c. injection. No tumor regression was seen. During infusions of 3 X 10(6) units over 2 h or 24 h, serum IL2 levels greater than or equal to 223 units/ml or 16 units/ml were maintained, respectively; with s.c. injection of 3 X 10(6) units, levels greater than 20 units/ml were maintained for 9 h. Marked lymphopenia was observed 24 h after the initiation of IL2 doses which was completely reversible when measured prior to the next dose. The lymphopenia was nonselective; T- and B-lymphocytes decreased in an IL2 dose-dependent manner, without consistent change in the OKT4:OKT8 ratio. No change was detected in monocyte expression of HLA-Dr or T-cell expression of the IL2 receptor. The in vitro generation of lymphokine-activated killer cytotoxicity decreased sharply and transiently shortly after i.v. doses. Mitogen responsiveness, delayed-type hypersensitivity, natural killer cytotoxicity, and mixed-lymphocyte reactivity were unchanged or decreased transiently shortly after IL2 doses. These studies help define the bioavailability of IL2 by i.v. or s.c. routes, and they will aid in the design of studies utilizing daily doses of IL2.
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PMID:Recombinant interleukin 2 toxicity, pharmacokinetics, and immunomodulatory effects in a phase I trial. 349 57

The infectious complications of bone marrow transplantation were reviewed in 43 adults, 22 of whom received transplants from HLA-matched donors without T-cell depletion and 21 of whom received donor marrow pretreated with the murine anti-T-cell monoclonal antibody CT-2 and complement. Recipients of HLA-mismatched, T-cell-depleted transplants had a higher rate of bacteremia (1.33 compared with 0.64 per patient, p = 0.05) and especially systemic fungal infections (0.92 compared with 0.14 per patient, p less than 0.001) than recipients of transplants from HLA-identical donors without T-cell depletion; two thirds of these infections occurred during the granulocytopenic period early after transplantation. Recipients of HLA-identical but T-cell-depleted transplants also had significantly more systemic fungal infections (0.77 per patient, p less than 0.001). T-cell depletion was associated with delayed engraftment, more prolonged granulocytopenia, and more severe lymphopenia and was shown by stepwise multivariate regression analysis to be the most powerful predictor of systemic fungal infection (r = 0.512, p less than 0.0001). Whereas ex-vivo T-cell depletion may reduce the risk of severe graft-versus-host disease, it may predispose the patient to infection, especially with fungi.
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PMID:Infectious complications in adults with bone marrow transplantation and T-cell depletion of donor marrow. Increased susceptibility to fungal infections. 351 42

We have recently developed a sensitive limiting dilution (LD) culture system to measure human alloreactive cytotoxic T lymphocyte precursors (CTL-p) in a given lymphoid cell population. We have now used this system to determine frequencies of donor HLA antigen-inducible CTL-p in the peripheral blood of human allograft recipients at various stages after transplantation. All patients (1 pancreas recipient and 9 kidney recipients) were on continuous cyclosporine treatment throughout the study. We report that, in patients with a well-functioning kidney graft (6/9), the number of donor-reactive CTL-p among peripheral blood lymphocytes decreased within 3-8 months after transplantation--in some cases (2/6) more than 10-fold. In contrast, frequencies of CTL-p with specificity for third-part HLA antigens remained largely unaltered in these patients. Furthermore, no decrease of donor-reactive CTL-p frequencies was seen in 3 of 4 patients showing clinical symptoms of graft rejection. These results indicate that functional clonal deletion of antigraft-reactive CTL-p may contribute to the state of graft tolerance in certain patients with a well-functioning kidney allograft.
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PMID:Selective reduction of donor-specific cytotoxic T lymphocyte precursors in patients with a well-functioning kidney allograft. 354 95

We applied the microlymphocytotoxicity method to the detection of lymphocytotoxic antibodies in case of 37 patients with acute malaria or 61 patients who sojourned in endemic malaria area and presented antibodies against plasmodial antigens (indirect immunofluorescence test greater than or equal to 1/20). Lymphocytotoxic antibodies were found in 16 patients of the first group and their occurrence may explain the lymphopenia and to a lesser extent the neutropenia and thrombopenia observed in some cases. In the second group lymphocytotoxic antibodies were present in 9 cases. In all samples no anti-HLA specificity was evidenced. Four patients were submitted to auto-cross-match test and 3 were found positive suggesting that among these antibodies some are auto-antibodies with anti-lymphocyte specificity.
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PMID:[Lymphocytotoxic antibodies in malaria]. 636 21

This study describes a series of immunological investigations carried out on a group of 37 HIV-seropositive children, aged 3-4 years, in two different stages of disease defined according to the CDC classification; the Primary stage, an asymptomatic one, showing abnormal immune function (P1-Class, B-Subclass) and the Secondary stage, 6-8 months later, in which patients exhibited non-specific findings, i.e., loss of weight, persistent generalized lymphadenopathy and hepatosplenomegaly, associated with abnormal immune function (P2-Class, A-Subclass). In both stages, immune function was considered 'abnormal' when lymphopenia and a decrease of the CD4/CD8-cell ratio were found. The phenotypes CD16+/56+ (NK) and HLA-DR+/CD3+ (T-activated?)-positive cells, were assessed by flow cytometry, and the following supplementary systemic humoral markers were investigated in homologus serum samples; total HIV(gp)-antibody, HIV(p24)-antibody and p24-antigen presence. If at the primary stage, no significant difference from to the reference values corresponding to the age was noticed, at the Secondary stage the obtained data is presented separately in two subgroups, namely the A-subgroup characterized by the presence of total HIV(gp)-antibody, the presence of HIV(p24)-antibody and the absence of p24-antigenaemia, and the B-subgroup, where total HIV(gp)-antibody was present, HIV(p24)-antibody absent and p24-antigenaemia present. A significant decrease of CD16+/56+ (NK)-cells was found within the two subgroups. As far as HLA-DR+ from CD(3+)-cells was concerned, only those within the B-subgroup showed a high percentage level, compared to the reference values. The importance of the present findings, linked to immune monitoring of HIV infection among children, is discussed.
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PMID:Changes of blood CD16/CD56 (NK) and HLA-DR/CD3-positive lymphocyte amounts in HIV-infected children, as related to clinical progression and p24-antigen/p24-antibody presence. 752 81

There is evidence suggesting that clinical manifestations and severity in systemic lupus erythematosus (SLE) are associated with age, sex and ethnicity. The influence of genetic factors, particularly HLA antigens, on disease expression is revealed by the diversity of clinical conditions in patients from different ethnic groups. The aim of this work was to analyze the impact of demographic factors on SLE expression in the Spanish population. Therefore, a retrospective analysis was undertaken of clinical records of 307 patients diagnosed in three Rheumatology Services, with a mean follow-up of 79 months. The distribution of clinical manifestations according to age and sex was studied and compared with those observed in other ethnic groups. The results show the influence of sex and age on our patient population. Thus, female had a higher frequency of malar rash, photosensitivity and lymphopenia. Males had a higher CNS and renal involvement. Patients under 15 years had a higher involvement of CNS and kidney. Patients under 15 years had a higher frequency of nephropathy, hematological, cutaneous and CNS changes. Patients older than 50 had a higher frequency of pleuropericarditis, but without renal involvement. Our ethnic group expressed a disease with a severity similar to that observed in north-european caucasians, higher than in north-american caucasians and lower than in south-american caucasians, asiatic and africans. In conclusion, patients with SLE from the south-european ethnic groups express a clinical picture with characteristics and severity similar to those observed in europeans from other latitudes and different from those reported in other ethnic groups.
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PMID:[Clinical and serological manifestations of 307 Spanish patients with systemic lupus erythematosus. Comparison with other ethnic groups]. 756 99

Autoimmunity during HIV-1 infection may contribute to the immunopathogenesis of AIDS. Titers of autoantibodies to HLA molecules and other surface markers of CD4+ T cells appear to increase with the progression of disease and may correlate with lymphopenia. Other autoantibodies are directed at a number of regulatory molecules of the immune system. Genesis of autoreactivity may be related to structural homologies of HIV-1 env-products to such functional molecules involved in the control of self-tolerance. The most impressive similarities include the HLA-DR4 and DR2, the variable regions of TCR alpha-, beta-, and gamma-chain, the Fas protein, and several functional domains of IgG and IgA. Thus, HIV-1 infection may induce dysregulation leading to autoimmune response, through a number of molecular mimicry mechanisms. Pathogenicity of antibodies to T cells could also include the activation of membrane-to-nucleus signal transducers resulting in increased apoptosis. The evolution of autoimmune mechanisms during HIV-1 infection cannot exclude, however, progression to immunoproliferative malignancy, since aspects of oligoclonal immune response to HIV-1 components may occur in several autoimmune diseases which in some instances evolve to lymphoma.
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PMID:Autoreactivity in HIV-1 infection: the role of molecular mimicry. 776 37

A 79-year-old woman of Mediterranean ascent suffered from corticosteroid-dependent chronic obstructive lung disease, hypogammaglobulinemia (IgG 1 and 2), decreased CD16 natural killer cell function and non-HIV related CD4 and CD8 lymphopenia. Such immunodeficiency could be either a variant of common variable immunodeficiency or an early stage of the idiopathic CD4 + T lymphocytopenia syndrome. She developed bilateral lesions of Kaposi's sarcoma on the lower extremities resembling the classic European type of the disease. The tumors contained both CD34 + and Factor XIIIa + cells. The HLA-DR5 haplotype was not found. Weekly low intravenous dosages of vinblastine improved the lesions but the patient died from pontic infarction.
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PMID:[Kaposi's disease in a female patient with acquired HIV-negative immunodeficiency]. 783 Dec 65

Blood counts of CD4 cells remain the best prognostic factor in patients infected with human immunodeficiency virus (HIV). However, the small number of infected cells contrasts with the importance of lymphocyte depletion. Several mechanisms might explain this depletion including: antibody-dependent cytotoxicity. Twenty to 50% of the antibodies produced in vitro by B lymphocytes are directed against HIV antigens, especially the gp120 and gp41 viral envelope antigen. If this cytotoxicity effect occurs in vivo, it could reduce of lymphocytes carrying the viral genome and partially explain the major lymphopenia in HIV-infected patients. It is not yet known whether the long-term effect of these antibodies is immunoprotective or deleterious, but they may play a protective role at least in the initial stages of the disease. autoimmunity. Sequence homology between the HLA II molecules and the glycoproteins of the viral envelope has been clinically and biologically documented in many manifestations of HIV infection. It has been suggested that alloreactivity, similar to the graft-versus-host reaction could be involved. In addition, programmed cell-death of the CD4 lymphocytes appears to be overactivated in HIV-positive subjects, possibly because the gp120 viral antigen perturbs the CD4-dependent signal for cell death. deleterious effects of cytokines. Tumour necrosis factor, for example, is known to play a role in the regulation of viral replication; it may favour the destruction of contaminated cells but also the initiation of provirus replication and integration into the cell genome. supra-antigens and/or infectious factors. Supra-antigenes, which can link with HLA molecules, are capable of oligoclonal activation without being "processed" in the cell presenting the antigen. This activation might affect cell death. Certain germ toxins could also play a role as cofactors. Cohort studies of asymptomatic HIV patients are needed to improve our understanding of these mechanisms. A therapeutic approach tailored to the stage reached by HIV-infected subjects will then be possible.
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PMID:[Mechanisms of lymphopenia in HIV infection]. 790 32


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