Biomedical subjects
Publications and source records attributed to J Clot.
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.
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Twenty selected patients suffering from severe, long-standing rhumatoid arthritis (RA) not controlled by anti-inflammatory drugs (19 cases) and from disseminated lupus erythematosis (DLE) (1 case) were treated with levamisole. The subjects were divided into 2 groups: Group I comprised fourteen patients (13 RA and 1 DLE) treated continuously by levamisole 150 mg/day for 3 or 6 months then on an intermittent regime (150 mg/day-3 days per week). Group II comprised 6 RA patients treated on the intermittent regime from the beginning. In Group I, following average treatment of 9 months (5-12 months), clinical results assessed according to precise clinical criteria were favorable in 9 out of eleven cases. In the other 2 cases no change was noted. Side effects included reversible agranulocytosis in 9 cases, on 3 occasions this necessitated the discontinuation of treatment. A signifcant reduction in sedimentation rate was noticed in 5 cases out of eleven and in 3 patients the Rose-Waller test turned negative. A monoclonal disglobulinemia of IgG lambda appeared under treatment in 1 patient who was deficient in IgA. Skin tests carried out periodically showed a significant augmentation of the response to candida. Lymphocyte culture in the presence of mitogens gave highly variable results from one control to the other in the same subject, as well as in the treated subjects as in the group of RA not receiving levamisole. These results are compared with those previously published; the mechanism of action and possible indications for levamisole in RA are discussed.
The quantitative study of lymphocyte populations is one means of approaching the immunological profile of patients with rheumatoid polyarthritis. In the present work we have studied the proportions of T and B lymphocytes in the blood and synovial fluid of 70 patients presenting classical or clearly defined rheumatoid polyarthritis. The number of T cells (E rosettes and anti HTLA serum) and B cells (membrane immunofluorescence and EAC rosettes) were found to be identical in both patients with rheumatoid polyarthritis and healthy subjects of the same age. On the other hand the number of "fast" rosettes, indicating a sub-population of T effector cells, and of EA rosettes formed at the expemnse of cells with a receptor for IgG Fc, are reduced in the blood and increased in the rheumatoid synovial fluid. In the course of rheumatoid polyarthritis there is therefore a displacement of certain lymphocytic sub-populations from the blood towards the synovial site where they are probably involved in lesional mechanisms.
Sixty patients with psoriasis have been studied for quantitative estimation of serum immunoglobulin A, G and M (60 cases), immunoglobulin E (43 cases), salivary immunoglobulin A (28 cases) and anti-IgG factors in the serum (40 cases). All the data have been statistically compared to a large control group (300 subjects). The results show an increase of the serum IgG and IgA means, an increase of salivary IgA which is correlated with the serum IgA, an increase of IgE levels in some patients and the presence of anti-IgG activity in the serum of 45% of patients with psoriasis. All these findings are statistically significant when compared to controls. These data could be in favour of auto-immune processes in psoriasis.
We have investigated lymphocyte subpopulations (six different markers) and T cell functions (mitogen responses and serum thymic factor determination) in twenty patients with psoriasis compared with thirty-five healthy subjects. Normal results were found for B cell markers, but significantly lower numbers of T cells were assessed by E-rosettes and anti HTLA serum. Mitogen responses were significantly higher in psoriasis than in normal subjects of the same age. These findings could be in favour of a T cell subpopulation defect involved in an auto-immune pathogenesis of psoriasis.
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Lymphocyte dependent-antibody cytotoxicity (LDAC) was studied in 29 patients with rheumatoid arthritis (RA) and 22 controls. A significant increase of cytotoxic index has been noted in RA patients (p less than 0.0001) whatever the ratio effector-target cells could be. There is a correlation between cytotoxic activity and so called "rheumatoid rosettes" (RR) level. This cytotoxic activity is linked to EA rosette forming cells without T cell markers or surface immunoglobulins, as shown by fractionation experiments. EA rosette forming cell depletion is followed by the disappearance of RR and a very important decrease of cytotoxic index. Cytotoxic activity is abolished after RR forming cell depletion while EA rosette level is nearly unmodified. RR forming cells belong to Fc receptor bearing lymphoïd population. They take place in EA rosette forming cell population. Increase of cytotoxicity in RA seems to be directly linked to these so called RR forming cells.
In the first part of this work patients with rheumatoid arthritis (RA), 36 cases and normal subjects, 49 cases have been studied by lymphocyte cultures stimulated by phytohaemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and Con A convalently bound to sepharose 4 B (Con A-S). The comparisons between the two groups have shown a significant difference between the RA lymphocytes and the control lymphocytes stimulated by PHA and Con A. However no statistical difference has been found between the two lymphocytes populations stimulated by PWM and Con A-S. In view to determining the lymphocyte population stimulated by each mitogen, separations of B- and T-cells from peripheral blood have been performed according to the ability for the T-cells population to bind the sheep red blood-cells (rosette forming cells). The T-cell rich population was only stimulated by PHA, Con A and PWM. Although the T-cell depleted one has shown no response to these mitogens, a response to Con A-S was elicited. In the second part of this work, patients with RA, patients with positive tuberculin (PPD) skin-tests and controls were studied. The lymphocytes from these groups were cultured in serum-free medium to obtain cell-free supernatants. These lymphocyte cultures were preincubated with the appropriate antigen or reconstituted after removal of the cells. Supernants from RA lymphocytes stimulated in vitro by undenaturated IgG induced an inhibition of the leucocyte migration, as well as the supernatants from tuberculin-sensitized lymphocytes. However, supernatants from non-RA lymphocytes or tuberculin-unsensitized lymphocytes did not show such an inhibition. These MIF like supernatants have been studied by Sephadex G-100 gel filtration. A MIF like activity has been found for PPD and IgG supernatants between the chymotrypsinogen (MW 23,000) and the lysozyme (MW 17,000). This MIF like activity could be due to RA lymphocytes stimulated by undenatured IgG.
The authors report a case of multiple kappa myeloma comboned with chronic lymphoid leukemia. The chronic lymphoid leukemia had evolved over a 13-year period in the classical manner, without serum or urnary monoclonal immunoglobulins. The multiple myeloma with blood and urinary kappa chains appeared suddenly with a typical clinical and radiological picture accompanied by renal insufficiency. Thd diagnosis was confirmed by the demonstration of both lymphocyte and plasmocyte cell proliferation and a study of the ultrastructure which showed the sarcomatous and secretory character of the plasmocytes. A study of plasmocyte subpopulation showed the proliferation of B lymphocytes. A combination of chronic lymphoid leukemia and multiple myeloma is exceptional. The physiopathological interpretation (mono or biclonal proliferation) is discussed in the light of current nosological conceptions concerning lymphoproliferative disorders.
The property of T cells to form rosettes with sheep red blood cells has been used to separate peripheral blood lymphocytes into purified T- and B-cell suspensions after density gradient centrifugation. A study of lymphocyte markers has shown that 2-6 per cent of E rosettes only were recovered in the B cell-enriched population. Lymphocyte stimulation in vitro was obtained with PHA, con A and PWM in unseparated and T-cell populations, but never in B-cell suspensions. Experiments of recombination between the two purified fractions have demonstrated that 10% of T cells added to B cells were able to induce a response to PHA and PWM. Otherwise, only T cells responded to allogenic stimulation. Lastly, B and T cells seemed to bind qualitatively and quantitatively the same mitogens on their membranes.
Patients with rheumatoid arthritis (RA), 36 cases, and normal subjects, 49 cases were studied by lymphocyte cultures stimulated by phytohemagglutinin (PHA), Concanavalin A (Con A), pokeweed mitogen (PWM) and Con A convalently bound to Sepharose 4 B (Con A-S). The comparisons between the two groups showed a significant difference between the RA lymphocytes and the control lymphocytes stimulated by PHA and Con A. However, no statistical difference was found between the two lymphocyte populations stimulated by PWM and Con A-S. In order to determine the lymphocyte population stimulated by each mitogen, separation of B and T cells from peripheral blood was performed according to the ability for the T cell population to bind the sheep red blood cells (rosette-forming cells). The T cell-rich population was only stimulated by PHA, Con A and PWM. Although the T cell-depleted population showed no response to these mitogens, a response to Con A-S was elicited.
The presence of a serum factor secreted by the thymus has been demonstrated in the serum of mice and man using a rosette inhibition assay. This factor is a peptide with a molecular weight close to 1,000. Its level is age dependent, being stable until the age of 6 months in mice and until 20 years in man. New Zealand Black mice show a premature cessation of thymic hormone secretion preceeding the onset of other T cell abnormalities and auto-immunity. Before any treatment the serum thymic hormone level is abnormally low in most cases of SLE even in patients under 25, an age where control subjects still show high hormone levels. Conversely, normal or high levels are found in RA, PARTICularly in patients over 40 who showed in 60% of cases a hormone level significantly higher than normal controls of the same age. In keeping with this data T cells evaluated by SRBC spontaneous rosette formation show low figures in some patients with active SLE and normal or high values in most cases of RA.
Patients with rheumatoid arthritis (RA), patients with positive tuberculin (PPD) skin-tests and controls were studied. The lymphocytes from these groups were cultured in serum-free medium to obtain cell-free supernatants. These lymphocyte cultures were pre-incubated with the appropriate antigen or reconstituted after removal of the cells. Supernatants from RA lymphocytes stimulated in vitro by IgG induced an inhibition of the leucocyte migration, as well as the supernatants from tuberculin-sensitized lymphocytes. However, supernatants from non-RA lymphocytes or tuberculin-unsensitized lymphocytes did not show such an inhibition. These MIF-like supernatants have been studied by Sephadex G-100 gel filtration. A MIF activity has been found for PPD and IgG supernatants between the chymotrypsinogen (MW 23,000) and the lysozyme (MW 17,000). This seems to agree with the classical region where MIF can be usually isolated.
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