Search PubMed⌕ Search

Biomedical subjects

J Clot

Publications and source records attributed to J Clot.

At least 73 records · Page 4Linked to original sources

Identification of class II HLA alloantibodies in placenta-eluted gamma globulins used for treating rheumatoid arthritis.

Placenta-eluted gamma globulins (PEGG) have been recently and successfully used in the treatment of patients with rheumatoid arthritis. PEGG, eluted at acid pH from large pools of human placentas, contained 99% IgG material. Sephacryl S300 gel filtration revealed a main fraction (76%) of native IgG accompanied by 10% aggregates and 14% digested fragments (as identified by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoelectrophoresis with specific antisera). Previous in vitro data had suggested that alloantibodies to class II HLA antigens were present in this preparation. This study confirms that PEGG and F(ab')2 fragments were able to inhibit stimulating cells in mixed lymphocyte reactions. Additional findings showed that: IgG from PEGG were cytotoxic for the non-T cell population; IgG or F(ab')2 from PEGG bound only to class II HLA-bearing cells; F(ab')2 from PEGG were able to block the complement-mediated cytotoxicity of anti-HLA-DR and anti-DQw1 alloantibodies. These data confirm the presence of class II HLA alloantibodies in PEGG. These antibodies may account for the clinical improvement reported in patients with rheumatoid arthritis. Our findings are similar to recent data showing that the injection of anti-Ia antibodies in experimental animal models decreases the autoimmune process.

Arthritis, Rheumatoid↗

[Effect of antibiotics on T lymphocyte responses].

T lymphocytes play a central role in the immune response. Coming from the bone marrow, they are attracted by the thymus where they are educated, they mature and differentiate into two main subsets: helper T-cells and suppressor/cytotoxicity T-cells. T lymphocytes are involved in the immune response at different levels. As "conductor" of the whole lymphoid system, they are able to recognize foreign antigens and to induce the activation and the regulation of other T-cells and also B cells by the way of many soluble factors named lymphokines. As effector cells of cell-mediated immune responses, they are able to provoke delayed type hypersensitivity reactions and to specifically kill target cells (anti-viral cytotoxicity, for instance). The in vitro effect of some antibiotics on T-cells has been investigated. Clearly, a lot of them are able to modulate T-cell functions.

Anti-Bacterial Agents↗

[Effect of cephalosporins on lymphocyte proliferation and immunoglobulin E production].

We studied the effects of three cephalosporins (cefadroxil, cefaclor, cephalexin) on an in vitro model of human mononuclear cell proliferation in response to polyclonal mitogens. Cefadroxil, and to a lesser extent cefaclor and cephalexin, induced a decrease of proliferative responses to phytohaemagglutinin and concanavalin A. This decrease was not due to a direct effect on lymphocytes, but depended on the presence of adherent monocytes in the cultures. Cephalosporins stimulated the release of prostaglandins E2 by monocytes, generating a suppressive activity. Cefadroxil and cephalexin were in vivo given to Brown-Norway rats sensitized to DNP-OVA to induce a primary and secondary IgE specific response. The administration of cefadroxil provoked a clear decrease of the secondary IgE response. As the IgE production closely depends on T suppressor cells, we hypothesize that cefadroxil could interfere with that production by stimulating a suppressor cell activity linked to an increased PGE2-release.

Animals↗

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↗

[Effects of piperacillin on the immunologic functions of macrophages].

In this study, the possible effects of piperacillin on three immune functions of human blood monocytes-macrophages were investigated. Monocytes and macrophages were isolated from the circulating blood of normal subjects by density gradient centrifugation followed by adhesion to plastic material. The cells were incubated for 30 to 60 min with different concentrations of piperacillin, then tested on the following models: presentation by the monocytes-macrophages of an exogenous antigen to autologous lymphoid cells, with evaluation of the proliferative response to tuberculin; secretion of interleukin-1 by monocytes-macrophages stimulated or not by lipopolysaccharide, with measurement of the culture supernatants ability to stimulate rat thymocytes; release to prostaglandin E2 by monocytes-macrophages with evaluation of its indomethacin-inhibitable suppressive effect on lymphoproliferative responses to a polyclonal mitogen. In none of these tests did piperacillin show and immunodepressant or immunostimulant effect.

Antigen-Presenting Cells↗

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↗

Human placenta-eluted gammaglobulins in immunomodulating treatment of rheumatoid arthritis.

Thirty-one patients with severe rheumatoid arthritis were treated with intravenous perfusion of human placenta-eluted gammaglobulins. These gammaglobulins, which are IgG eluted from placental tissue, have strong immunomodulating properties in vitro. Several clinical trials were tested to find the optimal useful dosage. A 50 percent improvement was considered a good result and was obtained in 60 percent of patients with rheumatoid arthritis. The best results were obtained in patients receiving 1,500 mg daily seven days each month. Six subjects had a long remission of their disease after the end of treatment. The side effects were usually minor. In all patients, an immunostimulation of lymphocyte function was shown, even when they had no improvement. A control group of patients underwent perfusion with IgG from placental blood without any clinical or immunologic effect. It is suggested that the in vivo effects of placenta-eluted gammaglobulins might be mediated by polyspecific anti-HLA-DR antibodies.

Adult↗

Peripheral blood T-cell subsets studied by monoclonal antibodies in type 1 (insulin-dependent) diabetes: effect of blood glucose control.

Peripheral T lymphocyte subsets were investigated, using monoclonal antibodies, in 14 patients with acute diabetes of duration less than 1 month (before insulin treatment) and after prolonged strict blood glucose control, and also in 40 healthy volunteers. At the time of diagnosis, the percentage total T cells was decreased (67.6 +/- 8.4 versus 72.8 +/- 6.6%), but T4 'helper' cells and T8 'suppressor/cytotoxic' cells were in the normal range. The T4/T8 ratio was not significantly higher than in the control group and B-cell percentages were increased (IgS: 18.3 +/- 7.1 versus 12.4 +/- 4.9%). The second T cell enumeration, performed after sustained normoglycaemia, showed a normal total T cell percentage and a decrease in the T4/T8 ratio depending on a decrease of T4 cells (38.3 +/- 12.8 versus 49.3 +/- 13.4), without any change of T8 lymphocytes; B cells remained elevated. These results suggest that insulin deficiency/metabolic derangement was responsible for an imbalance of circulating lymphocytes and underlines the importance of metabolic control in the assessment of such immunological parameters.

Adolescent↗

Immunological aspects of psoriasis. VI. Impairment of isoprenaline and theophylline-induced inhibition of mitogen responsiveness.

Pharmacological abnormalities occur in the psoriatic epidermis, and if similar abnormalities occur in the peripheral blood mononuclear cells they could impair the immune responses in psoriasis. In a paired control study, we have tested the capacity of histamine, isoprenaline and theophylline (10(-5) and 10(-7) M) to inhibit the mitogen responsiveness of blood mononuclear cells from normal and psoriatic subjects, using phytohaemagglutinin and concanavalin A. In the normal controls, mitogen responsiveness was inhibited by all three pharmacological agents by about 30 to 50%. In cells from psoriatic patients, the response in the presence of histamine was inhibited (as in the controls), but isoprenaline caused no inhibition, and theophylline paradoxically increased the mitogenic responses. These results suggest there is a defect in the pharmacological response of the blood mononuclear cells in psoriasis.

Adult↗

Decreased suppressor cell activity of alveolar macrophages in bronchial asthma.

In 8 allergic asthmatic patients and 12 healthy volunteers, we investigated the effects of alveolar macrophages (AM) on lymphoproliferative responses to polyclonal T-cell mitogens of autologous peripheral blood mononuclear cells (PBMC). The AM were obtained by bronchoalveolar lavage. Peripheral blood mononuclear cells (PBMC) and mitomycin-treated autologous bronchoalveolar cells (BAC) were cocultured at various AM-to-PBMC ratios, and were stimulated or not by phytohemagglutinin and concanavalin A. Half of AM expressed HLA-DR antigens in both the asthmatic and the control group. The BAC from normal subjects were able to modify the lymphoproliferative responses of autologous PBMC to cell mitogens. A dose-dependent effect was observed related to the number of BAC added to PBMC--suppressive at high ratios but enhancing at low ratios. In allergic bronchial asthma, there was a decreased suppressor cell activity of BAC. Among BAC the adherent cells were responsible for this effect. This abnormality could be a part of more general decreased functional activity of AM in allergic bronchial asthma.

Adolescent↗