Biomedical subjects

Youri Chanseaud

Publications and source records attributed to Youri Chanseaud.

9 recordsLinked to original sources

PubMed2005

Anti-annexin V antibodies: are they prothrombotic?

Annexin V inhibits prothrombin activation and is able to prevent thrombus formation under normal venous and arterial blood flow conditions. Antibodies to annexin V have been identified in association with several pathological conditions, including systemic lupus erythematosus (SLE) with or without anti-phospholipid syndrome, recurrent spontaneous abortions and systemic sclerosis (SSc). These antibodies are suspected to exert a detrimental role and interfere with annexin V function. Thus, they have been associated with the occurrence of foetal loss and venous and/or arterial thrombosis in SLE patients, as well as digital ischemia in SSc patients. However, their true pathogenic role remains to be proven.

Abortion, Habitual↗

PubMed2005

Analysis of autoantibody repertoires in small- and medium-sized vessels vasculitides. Evidence for specific perturbations in polyarteritis nodosa, microscopic polyangiitis, Churg-Strauss syndrome and Wegener's granulomatosis.

In order to identify new antibody reactivities, we have used a quantitative immunoblotting technique on extracts of normal human tissues to analyze the repertoires of serum IgM, serum IgG and purified IgG autoantibodies of patients with systemic vasculitides. Patients fulfilled the American College of Rheumatology and Chapel Hill criteria for the diagnosis of polyarteritis nodosa (PAN) (n=8), PAN related to hepatitis B virus (HBV) infection (n=5), Wegener's granulomatosis (WG) (n=6), microscopic polyangiitis (MPA) (n=18) or Churg-Strauss syndrome (CSS) (n=8). Sera from patients with chronic HBV infection without PAN (n=5) and age- and gender-matched healthy individuals (n=45) were used as controls. In the lung extract, IgM from 12/18 MPA patients reacted with high intensity with a 50 kDa band and serum IgG from 3/8 CSS patients bound to a 70 kDa protein band. In the artery extract, serum IgG from 6/18 MPA patients bound to an 85 kDa antigen, whereas purified IgG from all WG patients tested bound to a 28 kDa protein band and IgM from CSS patients bound to 2 main antigens of 38 and 60 kDa. These results provide evidence for the specificity of autoantibody repertoires from patients with PAN, WG, CSS and MPA.

Adolescent↗

PubMed2004

[Immunomodulatory effects of intravenous immunoglobulins].

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human IgG obtained from pools of more than 1000 healthy blood donors. They are currently used in the treatment of a wide range of auto-immune diseases, whether associated with auto-antibodies or auto-reactive T lymphocytes, as well as in the treatment of systemic inflammatory diseases. Several mechanisms of action have been identified during the last 20 years, including: (i) modulation of Fc receptors expression on leukocytes and endothelial cells; (ii) interaction with complement proteins; (iii) modulation of cytokines and chemokines synthesis and release; (iv) modulation of cell proliferation and apoptosis; (v) remyelinisation; (vi) neutralisation of circulating autoantibodies; (vii) selection of repertoires of B and T lymphocytes; (viii) interaction with other cell-surface molecules on lymphocytes and monocytes; (ix) corticosteroid sparing. These mechanisms of action are multiple and often intricate. However, they are still little known and further investigations are warranted.

Apoptosis↗

PubMed2004

IgG reactivity with a 100-kDa tissue and endothelial cell antigen identified as topoisomerase 1 distinguishes between limited and diffuse systemic sclerosis patients.

We have analyzed antibody (Ab) reactivities of patients with limited systemic sclerosis (SSc) and anti-centromere Ab, patients with diffuse SSc and anti-topoisomerase 1 (anti-topo 1) Ab, patients with diffuse SSc without anti-topo 1 or anti-centromere Ab and age- and gender-matched healthy controls with normal human tissue and endothelial cell (EC) antigens. IgG reactivities with tissue antigens differed significantly between patients with anti-topo 1 Ab and patients with anti-centromere Ab. One 100-kDa band identified as topoisomerase 1 in macrovascular and microvascular EC extracts was recognized by IgG from patients with anti-topo 1 Ab and 50% of patients without specific Ab. IgG from patients with limited SSc and anti-centromere Ab, but not those of other patients or controls specifically recognized a 80-kDa band only in microvascular EC. Our results indicate that Ab from patients with limited or diffuse SSc with or without anti-topo 1 Ab exhibit specific and mutually exclusive reactivity patterns.

Autoantibodies↗

PubMed2003

IgM and IgG autoantibodies from microscopic polyangiitis patients but not those with other small- and medium-sized vessel vasculitides recognize multiple endothelial cell antigens.

Using a quantitative immunoblotting technique on extracts of macrovascular and microvascular endothelial cells (EC), we analyzed serum IgM and IgG reactivities of patients with active disease fulfilling the ACR and Chapel Hill criteria for the diagnosis of polyarteritis nodosa (PAN) (n = 8), PAN related to hepatitis B virus (HBV) infection (HBV-PAN) (n = 5), Wegener's granulomatosis (n = 6), microscopic polyangiitis (MPA) (n = 18), Churg-Strauss syndrome (n = 8), and patients with chronic HBV infection without PAN (n = 5) and age- and gender-matched healthy individuals (n = 45). MPA patients' IgM bound to 200-, 105-, 80-, 65-, 45-, 35-, and 33-kDa major bands, whereas IgM from controls and other patients bound predominantly to the 65-kDa band in EC extracts. MPA patients' IgG reacted mainly with 105-, 70-, 55-, and 38-kDa protein bands, whereas IgG from controls and other patients did not. Our results provide evidence that IgM and to a lesser degree IgG from MPA patients specifically recognize multiple EC antigens.

Autoantibodies↗

PubMed2003

New insights into the pathogenesis of systemic sclerosis.

Systemic sclerosis (SSc) is a connective tissue disorder characterized by vascular abnormalities and excessive collagen synthesis. Extracellular matrix overproduction by fibroblasts results from abnormal interactions among endothelial cells, mononuclear cells (lymphocytes and monocytes) and fibroblasts, in a setting of vascular hyperreactivity and tissue hypoxia. Many autoantibodies have been identified in the sera of SSc patients; some of them are specific to the disease, such as anti-centromere antibodies in limited SSc, anti-topoisomerase 1 and anti-RNA polymerase I/III antibodies in diffuse SSc. Their pathogenetic role(s) remains uncertain. However, genetic, environmental and possibly alloreactive factors might also contribute to disease susceptibility.

Autoantibodies↗

PubMed2003

Polyreactive autoantibodies purified from human intravenous immunoglobulins prevent the development of experimental autoimmune diseases.

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human polyclonal Ig G (IgG) that exert immunomodulatory effects in patients with autoimmune or systemic inflammatory diseases. Two different IgG subfractions were evaluated for their respective immunomodulatory effects in the treatment of experimental autoimmune diseases: a fraction enriched in antibodies that recognize the F(ab')(2) portion of IVIg and a fraction of natural polyreactive autoantibodies purified on a dinitrophenyl (DNP)-Affiprep immunoadsorbent. A very small fraction of IgG interacting with DNP but not with F(ab')(2) fragments expressed an increased ability to bind to self-antigens. The anti-DNP fraction, but not the anti-idiotype fraction, protected against inflammation observed in collagen-induced arthritis and experimental autoimmune encephalomyelitis in rats. Furthermore, it was able to reduce the occurrence of spontaneous diabetes mellitus in nonobese diabetic mice at lower concentrations than unfractionated IVIg. The therapeutic benefit of the anti-DNP fraction was associated with the inhibition of secretion of proinflammatory cytokines and stimulation of secretion of IL-1 receptor antagonist. Our results provide evidence that polyreactive autoantibodies play a role in the protective effect of IVIg in experimental models of autoimmune diseases in which inflammatory reactions are part of the disease process.

Animals↗

PubMed2002

Mechanisms of intravenous immunoglobulin action in the treatment of autoimmune disorders.

Intravenous immunoglobulins (IVIg) are therapeutic preparations of normal human immunoglobulin (Ig) G obtained from pools of blood from more than 1000 healthy donors, and exert immunomodulatory effects in autoantibody-mediated and T-cell-mediated autoimmune disorders and systemic inflammatory diseases. IVIg mechanisms of action in autoimmune diseases have been extensively analysed during the last 15 years and include the following: (i) interaction of the IgG Fc fragment with Fc receptors on leucocytes and endothelial cells; (ii) interaction of infused IgG with complement proteins; (iii) monocyte and lymphocyte modulation of synthesis and release of cytokines and cytokine antagonists; (iv) modulation of cell proliferation and reparation; (v) neutralisation of circulating autoantibodies; (vi) selection of immune repertoires; and (vii) interaction with other cell-surface molecules on T and B lymphocytes.

Adjuvants, Immunologic↗

PubMed2002

[Pathogenesis of systemic scleroderma: immunological aspects].

Systemic sclerosis (SSc) is a connective tissue disorder that is characterized by excessive collagen synthesis by fibroblasts and by vascular hyperreactivity and obliteration phenomena. Excessive collagen production is the consequence of abnormal interactions between endothelial cells, fibroblasts and mononuclear cells. Immunological abnormalities are present very early in the development of SSc. Mononuclear cells, particularily macrophages and T lymphocytes play a prominent role in fibroblast activation and collagen synthesis through the cytokines they produce. Thus, lymphocytic infiltrates in the skin and in the lung are preferentially composed of CD8+ T lymphocytes, that produce important amounts of interleukin 4 (IL-4). The effects of IL-4 are added to these of transforming growth factor B (TGF-B) and connective tissue growth factor (CTGF) that stimulate collagen synthesis by fibroblasts. T lymphocytes produce important amounts of gamma interferon (INF-gamma) that is the best inhibitor of collagen synthesis by fibroblasts. However, the inhibitory effect of INF-gamma on collagen synthesis is diminished in SSc patients. Numerous autoantibodies can be evidenced in the serum of SSc patients. Three of them are specific for SSc and mutually exclusive: anti-centromere antibodies (Ab) in limited SSc, anti-Scl70 Ab in diffuse SSc and anti-RNA polymerase III Ab in diffuse SSc with renal involvement. These autoantibodies are good prognosis markers but their pathogenic role remains uncertain.

Autoantibodies↗