Regression of an expanded subpopulation of large granular lymphocytes in a patient with rheumatoid arthritis.
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Adult↗
Biomedical subjects
M Andary
Publications and source records attributed to M Andary.
Shifts in interleukin-4 and interferon-gamma production by T cells of patients with elevated serum IgE levels and the modulatory effects of these lymphokines on spontaneous IgE synthesis.
Interleukin-4 (IL-4) has been demonstrated to induce IgE synthesis by peripheral blood mononuclear cells (PBMNCs) of healthy donors. In this study, we demonstrated that IL-4 also can enhance spontaneous IgE synthesis by PBMNCs of allergic/atopic patients and patients with Buckley's or hyper-IgE syndrome. Spontaneous IgE production by PBMNCs of these patients was suppressed by interferon (IFN)gamma or IFN-alpha in a dose-dependent fashion. Despite high serum IgE levels, no IL-4 could be detected in the serum of the patients, but indirect evidence was obtained indicating that enhanced IL-4 production in vivo may be associated with the high serum-IgE levels in these patients. Spontaneous IL-4 production was measured in PBMNC cultures of 4/21 patients tested. Furthermore, spontaneous IgE synthesis by PBMNCs of three other patients of seven tested in vitro was partly blocked by anti-IL-4 antiserum. In addition, levels of soluble CD23 (which is specifically induced by IL-4) were strongly elevated in sera of patients. Finally, activation of PBMNCs of the patients resulted in levels of IL-4 and of IFN-gamma synthesis that were higher and lower, respectively, than levels produced by PBMNCs of healthy control donors tested in parallel. Collectively, our data indicate that spontaneous IgE synthesis in vitro can be modulated by IL-4, IL-5, IFN-gamma, and IFN-alpha. In addition, our data suggest that enhanced IL-4 and reduced IFN-gamma production is associated with the elevated serum IgE levels observed in these patients.
Antigens, Differentiation, B-Lymphocyte↗
Treatment of infantile spasms with intravenous gamma-globulins.
In a prospective study, 23 children with infantile spasms received intravenous gammaglobulins in high doses. 19 patients present a West syndrome. 4 older patients were included in the study because infantile spasms had preceded their Lennox-Gastaut syndrome. None of the patients had recently undergone corticosteroid therapy. No effect was observed in 15 patients, while transitory clinical and/or electroencephalographic improvement was noted in 3. Complete normalization was obtained in the remaining 5 patients, of whom 4 had severe brain lesions. No correlation existed between the therapeutic results and immunological abnormalities, a deficiency in IgG subclasses in particular. On the whole, the therapeutic results were disappointing. But the existence of some cases in which spectacular electroencephalographic and/or clinical improvement was obtained leads us to suggest that IV gamma-globulins be used as auxiliary treatment in infantile spasms.
Electroencephalography↗
Effect in vitro of a bacterial extract (OM-89) on interleukin 1 and interleukin 2 production by peripheral blood mononuclear cells from healthy subjects and rheumatoid arthritis patients.
The effect of a lyophilized extract from Escherichia coli strains (OM-89) on interleukin 1 and interleukin 2 production was studied by using peripheral blood mononuclear cells (PBMC) from healthy volunteers and from patients suffering from rheumatoid arthritis (RA) since, in this autoimmune disease, an abnormal cytokine network has been already described. The secretion of interleukin 1 (IL-1) was investigated in supernatants of monocytes purified by adherence, and measured by the C3H/HeJ thymocyte co-mitogenic assay. OM-89 was able to induce the secretion of IL-1 by normal and RA monocytes to about half of the level reached when the same cells were stimulated by lipopolysaccharide. The production of interleukin 2 (IL-2) was investigated in supernatants of PBMC, stimulated or not by phytohaemagglutinin (PHA) and mixed or not with various concentrations of OM-89. The level of IL-2 in supernatants, as measured by the stimulation of the CTLL2 murine cell line, was lower in RA supernatants than in control ones. In the presence of PHA and OM-89, the IL-2 production was enhanced and normalized in supernatants from RA patients. Such data may help to explain the clinical improvement previously reported in RA patients orally treated with OM-89.
Adjuvants, Immunologic↗
[Alteration of IgE production by cefadroxil].
The effect of two cephalosporins, cefadroxil and cefalexine, was in vitro studied by using two models of regulation of the IgE production in healthy humans, e.g. the induction of CD23-antigens on B-cells and the IgE synthesis in cell culture supernatants after stimulation by recombinant interleukin-4. Cefadroxil clearly inhibited CD23 membrane expression on normal human B-lymphocytes. In the same way, this cephalosporin blocked up to 90% of the in vitro interleukin-4-dependent IgE production by normal peripheral blood mononuclear cells. Cefalexine was unable to do the same. There results suggest that cefadroxil interplays with the regulation processes of the IgE production in humans.
Antigens, Differentiation, B-Lymphocyte↗
Increase of class II HLA molecules on the membrane of B lymphocytes from patients with rheumatoid arthritis.
Using a novel cytofluorometric method of cellular antigen quantification, we examined peripheral blood mononuclear cells (PBMC) from patients suffering from rheumatoid arthritis (RA) for quantitative modification of class II human leucocyte antigen (HLA) molecules expressed on the surface. Class II HLA molecules were detected by indirect immunofluorescence with a monomorphic monoclonal antibody. No change was observed in the density of class II HLA molecules at the surface of monocytes of RA patients as compared to that of paired healthy subjects. We confirmed that the percentage of class II HLA-bearing T cells was slightly increased in RA patients versus controls, but the density of class II antigens per cell could not be determined accurately. An increase in the density of class II HLA molecules on RA B cells was shown, suggesting that a chronic activation stage of this population contributes to the disease.
Antigens, Surface↗
Regulation of interleukin-2 production in rheumatoid arthritis.
The regulation of interleukin-2 (IL-2) production was investigated using mononuclear cells from synovial fluid (SF) and peripheral blood of 12 patients with classical and active rheumatoid arthritis. Decreased phytohemagglutinin (PHA) stimulated IL-2 production by lymphocytes was observed in rheumatoid peripheral blood (5.3 +/- 10.9 units/ml) and SF (3.8 +/- 5.2 units/ml) compared to peripheral blood from 12 normal donors (18.1 +/- 15.4 units/ml) and SF from 5 patients with other rheumatic diseases (11.9 +/- 10.9 units/ml). Indomethacin, phorbol myristate acetate and irradiation of suppressor cells increased IL-2 values in rheumatoid SF and peripheral blood but did not restore normal IL-2 production. IL-2 production did not correlate with clinical activity in patients with RA.
Adolescent↗
[Characterization of chronic lymphocytic proliferation in a female patient having rheumatoid polyarthritis with neutropenia].
The authors have studied the case of a female patient with rheumatoid polyarthritis, who developed a lymphocytic proliferation in the blood, the marrow, and the liver, associated with a neutropenia. Several similar cases have been recently reported in the literature. The cellular proliferation is made of large granulous lymphocytes and the study of membrane markers enables to find the following homogeneous phenotype: E rosette+, CD8+, HNK-1+, FcR+, CD4-luminal diameter "divided by degrees - -, IgS-, HLA class II-. This lymphocytic sub-population produces little interleukin-2, responds weakly to mitogens (PHA, CON A, PWM), and inhibits the response of normal lymphocytes to the same mitogens. These lymphocytes have a weak natural killer activity but, on the contrary, develop a very strong cytotoxic activity which is antibody-dependent. Clinically, splenomegaly, anemia and infections are frequent and hepatomegaly or thrombopenia more rare. Adenopathies are never present. The evolution is chronic in nature and not very aggressive, although the lymphocytic proliferation is monoclonal in origin, as demonstrated in molecular biology studies. The neutropenia might be secondary to an inhibiting effect of lymphocytes on the granular precursors of the bone marrow. There is a definite association between this lympho-proliferative syndrome and rheumatoid polyarthritis, and this association appears to be different from the Felty's syndrome.
Adult↗
Characterization of an expanded subpopulation of large granular lymphocytes in a patient with rheumatoid arthritis.
We describe a rheumatoid arthritis patient who was found to have chronic T cell lymphocytosis and neutropenia. She had an increased number of lymphocytes in the peripheral blood, bone marrow, and liver, and the expanded lymphocyte subset consisted of large granular lymphocytes with a homogeneous phenotype. Of the previously described patients with these large granular lymphocytes, almost one-fourth have had rheumatoid arthritis.
Adult↗
[Phenotype and functions of chronic lymphocyte proliferation associated with neutropenia in a female patient with rheumatoid arthritis].
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Adult↗
[Classical Kaposi's disease: immunological study].
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Humans↗
Circulating lymphocyte subpopulations in juvenile insulin-dependent diabetes. Correction of abnormalities by adequate blood glucose control.
Circulating lymphocytes from 39 juvenile insulin dependent diabetics of recent onset were studied by six membrane marker techniques and mitogen stimulation. Well controlled (n = 14) were grouped separately from poorly controlled (n = 25) patients. The total lymphocyte counts were not different from 50 control subjects. The percentage of T-cells detected by erythrocyte rosettes and B-cells detected by erythrocytes--antibody--complement rosettes was significantly decreased only in poorly-controlled diabetics (64.1 +/- 1.3 and 9.7 +/- 1.8, vs 71.0 +/- 1.0 and 15.3 +/- 0.6 in controls). Cells bearing receptors for the Fc fragment of IgG immunoglobulins were decreased in both groups. Mitogen stimulation was not different from controls but was significantly lower in poorly controlled than in well controlled diabetics. Optimal blood glucose control for 5 +/- 2 days using an external artificial pancreas led to a rapid normalisation of membrane marker values and mitogen responsiveness of lymphocytes from previously poorly controlled diabetics. Separate in vitro experiments showed that glucose had an inhibitory effect on mitogen stimulation at concentrations greater than or equal to 8.3 mmol/l and on T- and B-lymphocyte numbers at concentrations greater than or equal to 55.6 mmol/l. DL 3-hydroxybutyrate tested at 17.1 and 34.2 mmol/l only depressed mitogen responsiveness. Such results suggest a rapidly reversible T-cell defect closely linked to the existing metabolic disturbances.
Adolescent↗
[Suppressor cells of mitogen responses during rheumatoid polyarthritis].
The suppressor activity of mononuclear cells of the peripheral blood (MCPB) during rheumatoid polyarthritis (RP) was studied using experimental protocole. The MCPB stimulated in vitro by concanavaline A (Con A) are capable of suppressing the mitogenis response of autologus cells; moreover, the short-lived spontaneous suppressor cells disappear during 24 hour in vitro incubation that determines an increase in the proliferative response of the incubated cells for 24 hours. In two of the six RP studied, the suppressor activity generated Con A and the spontaneous suppressor activity are nul. Culture experiments with the MCPB of PR and control subjects show that this defect in suppressor activity is more related to a problem in the generation of suppressor cells than to a deficiency in the response to suppressor signals.
Arthritis, Rheumatoid↗
Evaluation of lymphocyte subpopulations and T-cell functions in psoriasis.
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Adolescent↗
Immunologic aspects of psoriasis. III. Fc-gamma-receptor bearing mononuclear cells in peripheral blood.
An anti-IgG activity has previously been reported at the cellular level in patients with psoriasis. This activity was demonstrated by the so-called 'rheumatoid' rosette test. In the present work the nature of 'rheumatoid' rosette-forming cells was studied in comparison with other EA rosette techniques. The use of purified cell populations showed that the lymphocytes participating in the 'rheumatoid' rosette phenomenon were lacking conventional T and B cell membrane markers, and were thus referred to as null cells. Such mononuclear cells bearing a receptor for the Fc part of IgG were able to act as killer cells to IgG-coated target cells. The cytotoxic activity was mainly restricted to a small proportion of lymphocytes forming 'rheumatoid' rosettes which had a high avidity for EA complexes. Such cytotoxicity could contribute to the aetiology of lesions in psoriasis.
Antibody-Dependent Cell Cytotoxicity↗
[Fc-gamma-receptor cells and rheumatoid arthritis].
Certain blood lymphocytes of patients suffering from rhumatoid arthritis (RA) and or control subjects, can be detected using a rosette technique in the presence of erythrocyte antibody compounds (EA). The EA rosettes demonstrate the presence of cells having a receptor for the Fc fragment of the IgG's (Fc-receptor). A significant increase in highly active EA rosettes during RA was demonstrated using six EA compounds differing according to the type of erythrocyte and the quantity of sensitizing antibody. These highly active EA rosettes correspond to the case in which few antiserum molecules cover the erythrocytes. Their high level in RA may correspond to an increased number of Fc-receptor cells or to a stronger linkage of EA compounds. The cells forming EA rosettes are responsible for the resulting cell antibody cytotoxicity that seems to change little during rhumatoid disease. However, the very special behavior of Fc-receptor lymphocytes incubated in vitro suggests that the IgG receptors are modulated by the immune compounds present during RA.
Adult↗
In vitro immunological studies in atopic and contact dermatitis.
Serum immunoglobulins, five lymphocyte markers and three mitogen assays were used in an investigation of 20 patients with atopic dermatitis. A slight impairment of the cell-mediated immunity was detected. Ten patients suffering from contact dermatitis had sub-normal lymphocyte reactivity.
Adolescent↗