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)

IgG anti-lymphocyte antibodies (ALA) reactive with resting lymphocytes were demonstrated in sera of patients with systemic lupus erythematosus (SLE) by immunofluorescence and flow cytometry and were shown (i) to bind T cells by non-Fc receptor-related mechanisms, (ii) to potentiate antibody-dependent cellular cytotoxicity (ADCC) of lymphocytes in vitro which correlated with binding to T cells, and (iii) to occur at a similar frequency in 29 SLE sera (56%) as IgM ALA (59%). IgG ALA levels in sera negatively correlated with absolute numbers of circulating lymphocytes in patients (r = -0.48, P less than 0.05), as did IgM ALA levels (r = -0.54, P less than 0.05); however, a stronger correlation resulted when levels of both ALA isotypes were considered together (r = -0.61, P less than 0.01). Different groups of SLE patients were distinguished with respect to relative serum content of IgM and IgG ALA and corresponding serum capacity to predominantly mediate ADCC, complement-dependent cytotoxicity (CDC), or both. No correlation existed between serum ADCC and CDC activities in vitro (r = 0.22). However, SLE patient lymphocyte counts negatively correlated with ADCC (r = -0.59, P less than 0.01) and to a lesser but still significant extent with CDC (r = -0.47, P less than 0.05). The latter results suggested that ADCC, induced by serum IgG ALA, was a mechanism of cytoloysis which occurred independently of CDC and which, like CDC, was significantly associated with lymphopenia in vivo.
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PMID:Isotype and cytotoxicity spectra of anti-lymphocyte antibodies in patients with systemic lupus erythematosus. 331 37

Population dynamics of bovine peripheral blood leukocyte subpopulations were quantitated following a primary bovine herpesvirus-1 (BHV-1) infection. Percoll isolated peripheral blood mononuclear cell (PBMC) subpopulations were analyzed using flow cytometry (FC) and cytochemical stains. Between days two to eight post-infection (PI) there was a significant decrease in the percentage of T-cells and nonT/nonB cells which was accompanied by an increased percentage of B-cells and monocytes. These percentages were extrapolated to the number of Percoll isolated PBMC during this period. A decrease in the T-cell population was the primary cause of the observed lymphopenia and a relative increase in the percentage of B-cells. The increased percentage of monocytes was caused by an increased number of circulating monocytes. These monocytes were characterized by an increase in Fc receptor expression, a decrease in plastic and Sephadex-G10 adherence and no apparent change in the level of class II MHC antigen (Ia) expression. Serum cortisol was significantly elevated on day 2 PI and may have been responsible for both the reduction in circulating T-cells and a decrease in the in vitro viability of peripheral blood lymphocytes. The percentage of Ia positive PBMC was increased significantly on day 4 PI. However, on days 4 and 6 PI the summated percentages of monocytes and B-cells (total Ia expressing population) exceeded significantly the actual percentage of Ia positive cells. This apparent suppression of Ia expression did not coincide with the elevated serum prostaglandin E2 concentrations on days 8 and 10 PI.
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PMID:Bovine peripheral blood leukocyte subpopulation dynamics following a primary bovine herpesvirus-1 infection. 350 48

The use of T cell subtyping to distinguish rheumatoid arthritis (RA) from systemic lupus erythematosus (SLE) was evaluated. We determined the distribution of IgG Fe receptor T cells (TG), IgM Fc receptor T cells (TM), and T cells lacking Fc receptors (Tnull) in 17 patients with RA and 7 patients with SLE. All RA patients including 3 antinuclear antibody positive-rheumatoid factor negative cases had normal numbers and percentages of TG, TM, and Tnull, whereas all SLE patients had a relative and absolute deficiency of TG. This TG lymphopenia was a better discriminator for SLE (7 of 7 SLE, 0 of 17 RA) than anti-DNA antibodies, hypocomplementemia, circulating immune complexes or total number of T cells.
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PMID:The use of T cell subtyping to distinguish rheumatoid arthritis from systemic lupus erythematosus. 697 81

Radiolabeled antibodies have shown promise for the treatment of lymphoma and for solid tumor targeting. Campath-1H is a humanized monoclonal antibody that reacts with the CD52 antigen present on human lymphoid and myeloid cells. Campath-1H is a gamma1 (G1) isotype that induces lymphopenia via an Fc-mediated mechanism(s). Isotype switches were engineered, and the resulting antibodies were expressed in NS0 mouse myeloma cells and biosynthetically radiolabeled with [35S]methionine. The forms included G1, G4, and a G4 variant that contained alanine substitutions at (EU numbering) Leu-235, Gly-237, and Glu-318. All isotypes bound antigen equivalently as assessed by target cell binding in vitro. The G4 variant had a greatly reduced capacity to interact with Fc receptor by virtue of reduced binding to THP-1 human myeloid cells and by a 1000-fold increase in EC50 to intermediate antibody-dependent cellular cytotoxicity. The pharmacokinetics of the isotypes were compared in CD-1 (nu/nu) mice bearing an experimental antigen-expressing tumor. The plasma half-life and tumor uptake were increased for the G4 variant. The G4 variant showed significantly less spleen, liver, and bone uptake but similar uptake in the lung, kidney, and stomach and lower tissue-to-blood ratios. Immunogenicity was assessed after repeated monthly administrations of unlabeled antibody in BALB/c mice. A 50% reduction in the incidence of anti-globulin response was observed for the G4 variant. These properties suggest that antibodies with reduced Fc receptor interaction merit additional study as potential targeting vehicles relative to other isotypes for radioimmunotherapy or situations where diminished normal tissue binding contributes to efficacy.
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PMID:Improved biodistribution, tumor targeting, and reduced immunogenicity in mice with a gamma 4 variant of Campath-1H. 861 27

Anti-CD3 monoclonal antibody (mAb) OKT3 is immunosuppressive, but causes severe adverse effects during the first administration ("first-dose reaction"). These adverse effects are presumably caused by cytokine release that results from T-cell activation. In vitro, T-cell activation by anti-CD3 mAb requires interaction with monocyte Fc receptors. The Fc receptor for murine IgG1, Fc gammaRIIa, is polymorphic. In some individuals, murine IgG1 anti-CD3 mAb causes T-cell proliferation and cytokine release in vitro (high responders [HR]), whereas in individuals with the low-responder (LR) phenotype it does not. We have now investigated the role of this Fc gammaRIIa polymorphism in the release of cytokines in vivo and the occurrence of adverse effects after the administration of WT31, a murine IgG1 anti-CD3/T cell receptor mAb. WT31 caused an increase of plasma tumor necrosis factor-alpha in all four HR patients and none of the five LR patients. In all HR patients except one, plasma gamma-interferon and interleukin 6 also increased, and a first-dose response was observed, whereas no cytokine release or adverse effects occurred in any of the LR patients. WT31 caused lymphopenia in all HR and none of the LR patients. FACS analysis demonstrated that in HR patients, after the initial disappearance of CD3+ cells from peripheral blood, modulation of CD3 occurred, whereas in LR patients a high degree of coating of the lymphocytes was observed. Surprisingly, WT31 also induced a marked granulocytopenia, as well as a decrease of thrombocytes, in three of the four HR patients (and in none of the LR patients). These data provide direct clinical evidence that Fc receptor interaction determines the release of cytokines and the occurrence of adverse effects after administration of anti-CD3/T cell receptor mAb. Furthermore, these data suggest that tumor necrosis factor-alpha by itself is not sufficient to induce the first-dose reaction.
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PMID:Role of polymorphic Fc receptor Fc gammaRIIa in cytokine release and adverse effects of murine IgG1 anti-CD3/T cell receptor antibody (WT31). 900 Jun 70