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Biomedical subjects

P Miossec

Publications and source records attributed to P Miossec.

158 records · Page 9Linked to original sources
PubMed1981

[Myasthenia gravis and asymptomatic monoclonal gammapathy. Detection of autoantibody activity of the monoclonal immunoglobulin].

Simultaneous occurrence of "myasthenia gravis" and monoclonal "asymptomatic" gammapathy has been observed in a 83 years old patient. Antistriated muscle antibodies could be detected at a level of 1/1,000 but no antiacetylcholine receptors antibodies. The antibody activity is located both in the monoclonal IgG kappa and in the polyclonal IgG. This case illustrates the frequent occurrence of several auto-immune disorders in a same patient.

Aged↗
PubMed1981

Effect of folic acid deficiency on nonspecific immunity (phagocytic activity and nitroblue - tetrazolium reduction).

Fifty three critically ill patients (two of the following criteria : thyroxin - binding - prealbumin less than or = to 24 mg/dl, creatinin - height - index less than or = to 80 percent and transferrin less than or = to 225 mg/dl) were divided into two groups according to the level of folic acid (FA). Group A consisted of 29 with FA less than or = to 3 ng/ml and group B of 24 with FA greater than 3 ng/ml. The phagocytic activity (PA) was significantly lower in group A and significantly corrected by AB sera, whereas the NBT reduction capacities were within the normal range. A correlation is shown between PA and level of FA as well in autologous sera as in AB sera.

Adult↗
PubMedDate not supplied

Generation and characterization of a human monoclonal autoantibody that acts as a high affinity interleukin-1 alpha specific inhibitor.

Interleukin-1 (IL-1) defines two polypeptides, IL-1 alpha and IL-1 beta, that possess a wide spectrum of biological effects. Two natural antagonists of IL-1 action have been characterized: the IL-1 receptor antagonist (IL-1Ra) and a soluble form of the type II IL-1 receptor. Neutralizing autoantibodies to IL-1 alpha have also been detected in sera of healthy individuals and patients with autoimmune or inflammatory diseases. To characterize such antibodies molecularly, we attempted to generate B cell clones producing anti-IL-1 alpha human monoclonal antibody (HuMAb) by combining Epstein-Barr virus-immortalization and CD40-activation of B lymphocytes from individuals with circulating anti-IL-1 alpha. We describe herein the generation and properties of a natural IgG4/kappa anti-IL-1 alpha monoclonal autoantibody, HuMAb X3, that bound specifically to human IL-1 alpha, but not to IL-1 beta and IL-1Ra, with a high affinity (Kd = 1.2 x 10(-10)M). HuMAb X3 inhibited IL-1 alpha binding to IL-1 receptors and neutralized biological activities of both recombinant and natural forms of IL-1 alpha. A recombinant form of HuMAb X3 was found to display identical specific IL-1 alpha antagonism. The presence of somatic mutations within X3 variable regions suggests an antigen-driven affinity maturation. This study extends the demonstration of the presence of high affinity neutralizing anti-IL-1 alpha autoantibodies that can function as a third type of IL-1 antagonist.

Amino Acid Sequence↗
PubMedDate not supplied

Switch in chemokine receptor phenotype on memory T cells without a change in the cytokine phenotype.

Th1 and Th2 cells as defined by their cytokine profile are associated with the expression of the chemokine receptors CCR5 and CCR3, respectively. In committed human memory Th1 cells the cytokine profile is irreversibly expressed. However, it is not known if the chemokine receptor phenotypes of Th1 and Th2 cells are permanently associated to the cytokine profile or if it can be changed. To analyze the possibility of inducing a switch in chemokine receptor phenotype on memory Th cells we used differentiated memory Th cells isolated from synovial tissue (ST) samples of patients with rheumatoid arthritis (RA). Freshly isolated T cells, T-cell lines and T-cell clones from these tissues were manipulated with Th1 (interleukin (IL)-12 + anti IL-4) or Th2 (IL-4 + anti IL-12) inducing conditions. The surface expression of CCR5 and CCR3 was analyzed by flowcytometry and interferon (IFN)-gamma and IL-4 production by ELISA. A Th1-inducing cytokine environment increased the expression of CCR5 in Th1 cells and induced the expression of CCR5 in Th2 cells as compared to culture condition with only IL-2. Induction of CCR5 expression on Th2 clones was associated with secretion of some IFN-gamma. Moreover, the Th2-associated chemokine receptor CCR3 could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture conditions with IL-4. This expression of CCR3 was associated with a reduced IFN-gamma production, but no IL-4 production could be induced. The IL-4-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, the same IL-12-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker CCR3 on memory Th1 cells demonstrates that a change in chemokine receptor phenotype related to the Th2 type can be induced on terminally differentiated Th1 cells, without a change in the cytokine profile.

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Cartilage and synovial membrane].

The synovial membrane acts on the cartilage at the levels of the synovial cells, the production of soluble factors and the cartilage components. The synovial membrane is at the same time a trophic, an immunologic and a defense organ. One does not oppose anymore the aspects found in normal synovium to those found in osteoarthritis and in rheumatoid arthritis. Synovial reactivity against the cartilage components is mediated by specific initiating mechanisms leading to an amplification process. Various soluble factors regulate this cooperation at the articular and the systemic levels. The dysregulation between these factors plays a role in the pathogenesis of joint diseases.

Cartilage, Articular↗
PubMedDate not supplied

Pro- and antiinflammatory cytokine balance in rheumatoid arthritis.

High levels of proinflammatory cytokines such as IL-1, TNF-alpha and IL-6 are produced by the rheumatoid synovitis. These cytokines, mainly produced by monocytes/macrophages, are thought to play a major role in chronic inflammation and in the final joint degradation. IL-4, IL-10, and IL-13 have been classified as antiinflammatory cytokines as they inhibit the production of the proinflammatory cytokines by monocytes. Acting on the balance between these two groups of cytokines may lead to new therapeutic approaches to controlling chronic inflammation without interfering at the level of the antigen.

Animals↗
PubMedDate not supplied

[Physiopathology of rheumatoid polyarthritis].

Rheumatoid arthritis is the most common and most severe form of inflammatory arthritis. Its exact aetiology remains unknown but the combination of various risk factors is involved. Two non mutually exclusive concepts have been suggested: one based on the primary contribution of T cells and the other on that of mesenchymal fibroblastic cells. Both initial pathways lead to a common pathway inducing an intra-articular inflammatory reaction which is non-antigen specific. This process results from the combination of an increased production of destruction-inducing cytokines with a reduced expression of regulatory factors with anti-inflammatory properties. These components represent targets for treatment which are now going through extensive clinical investigation.

Arthritis, Rheumatoid↗
PubMedDate not supplied

[Cell adhesion molecules and pharmacologic applications. Round Table No 3 at Giens XIII].

This workshop intended to perform a "state-of-the art" of current research on adhesion molecules in various pathophysiologies, and to determine pharmacological targets. Indeed, recent important progress concerning the cellular and molecular physiology of adhesion molecules led to the development of various integrin antagonists in several domains, like cardiovascular disease, inflammation and cancer. Integrins play a major role in numerous process like embryonic development, tumor growth and metastasis, apoptosis, hemostasis, leucocyte recruitment and activation, and bone resorption. The development of integrin antagonists is well advanced in the cardiovascular domain, since the first marketed drug (abciximax, Reopro) is an antibody directed against the GPIIb/IIIa complex (integrin alpha IIb/beta 3) involved in the final pathway of platelet aggregation. Another active domain of research in pharmacology is 'cardioprotection', i.e. the prevention of cardiac damages induced by the reperfusion of the coronary bed after an ischemia secondary to thrombolysis, angioplasty, of coronary bypass. The pharmacological targets of these antagonists are integrins involved in various process like leucocyte and platelet adhesion and endothelial function. Other potential indications in the cardiovascular field are restenosis after angioplasty, and atherosclerosis.

Cardiovascular Diseases↗