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Biomedical subjects

Luc Mouthon

Publications and source records attributed to Luc Mouthon.

51 records · Page 3Linked to original sources
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

Lymphoma complicating common variable immunodeficiency with granulomatous disease: report of two cases.

Common variable immunodeficiency (CVID) is a primary defect that is characterized by impaired antibody production. CVID patients may develop recurrent infections, autoimmune disorders and/or systemic granulomatosis. It is well documented that CVID patients are at risk to develop malignant lymphomas. However, to the best of our knowledge, lymphoma complicating the course of CVID associated with systemic granulomatosis has never been reported. We describe two CVID patients with systemic granulomatosis who developed B-cell lymphomas, one related to Epstein Barr virus infection, 5 and 12 yr after CVID had been diagnosed.

B-Lymphocytes↗
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↗
PubMed2003

[Investigation of the complement system in clinical practice].

The complement system plays an important role in defence of the host against infection and in the clearance of immune complexes. Defects in complement proteins are often associated with infections or auto/immune complex diseases. Investigation of complement is useful for diagnosis and following of auto-immune diseases. The aim of this Article is to provide an overview of important applications of complement in medicine, emphasizing the role of complement in pathogenesis and the usefulness of measurements of complement proteins in diagnosis and assessment of the evolution of disease states. Emphasis has been placed on practical applications and understanding basic mechanisms of disease. The best screen for complement deficiencies or significant activation is the CH50, which measures total classical pathway activity and the measurement of C3 and C4. The absence or decrease of multiple components is usually due to consumption of complement. Complete lack of CH50 associated with normal C3 antigen is a strong indication for complement deficiency and should be followed up with further tests to determine which component is missing.

Angioedema↗
PubMed2002

[Treatment of scleroderma].

No single therapeutic agent has been shown to increase survival of patients with systemic scleroderma in a prospective randomized trial. Drugs as colchicine and D-penicillamine are disappointing. Conversely, disease modifying agents are emerging such as cyclophosphamide in interstitial pulmonary disease, and stem cell autograft after high dose cyclophosphamide therapy in patients who develop visceral involvement in the three first years of evolution of the disease is under study. Organ specific therapy may show significant benefit, such as angiotensin converting enzyme inhibitors in renal crisis and epoprostenol in primary pulmonary hypertension.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Inhibition of maturation and function of dendritic cells by intravenous immunoglobulin.

Normal immunoglobulin G for therapeutic use (intravenous immunoglobulin [IVIg]) is used in an increasing number of immune-mediated conditions, including acute and chronic/relapsing autoimmune diseases, transplantation, and systemic inflammatory disorders. Several mutually nonexclusive mechanisms of action account for the immunoregulatory effects of IVIg. Although IVIg inhibits T-cell proliferation and T-cell cytokine production, it is unclear whether these effects are directly dependent on the effects of IVIg on T cells or they are dependent through the inhibition of antigen-presenting cell activity. Here, we examined the effects of IVIg on differentiation, maturation, and function of dendritic cells (DCs). We show that IVIg inhibits the differentiation and maturation of DCs in vitro and abrogates the capacity of mature DC to secrete interleukin-12 (IL-12) on activation while enhancing IL-10 production. IVIg-induced down-regulation of costimulatory molecules associated with modulation of cytokine secretion resulted in the inhibition of autoreactive and alloreactive T-cell activation and proliferation. Modulation of DC maturation and function by IVIg is of potential relevance to its immunomodulatory effects in controlling specific immune responses in autoimmune diseases, transplantation, and other immune-mediated conditions.

Cell Culture Techniques↗
PubMed2002

Prevalence of monoclonal gammopathy in patients presenting with acquired angioedema type 2.

PURPOSE: Acquired angioedema type 1 is characterized by a C1 inhibitor deficiency in patients with lymphoproliferative disorders, whereas acquired angioedema type 2 is characterized by anti-C1 inhibitor antibodies, and has not been thought to be associated with lymphoproliferative disease. We studied the clinical features, complement profiles, and associated diseases in 19 new patients with diagnosed acquired angioedema type 2. SUBJECTS AND METHODS: Plasma concentrations and functional activity of complement components were measured by conventional techniques. Functional C1 inhibitor activity was assessed by a chromogenic assay. Autoantibodies to C1 inhibitor were detected using an enzyme-linked immunosorbent assay. RESULTS: The 11 men and 8 women (median age, 60 years) presented with recurrent attacks of angioedema. All patients had detectable anti-C1 inhibitor antibodies in serum. A monoclonal gammopathy was detected in 12 patients (63%) at the time of diagnosis, 11 of whom had an immunoglobulin peak of the same heavy- and light-chain isotypes as the acquired anti-C1 inhibitor antibody. Three of these 12 patients developed a malignant lymphoproliferative disease. CONCLUSION: As with type 1 disease, a large proportion of patients with acquired angioedema type 2 have a lymphoproliferative disorder.

Age Distribution↗
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

[Psychiatric manifestations of systemic sclerosis].

Systemic sclerosis (SSc) is a rare conjuctive tissue disorder that is characterized by fibrosis of the skin and internal organs as well as vascular obliteration phenomenons. SSc is responsible for increased morbidity and mortality, and skin fibrosis may be responsible for major body changes. These phenomenons may contribute to the occurrence of psychological disturbances such as anxiety and depression, whereas the incidence of psychotic symptoms is very low in SSc patients. However, the prevalence of psychiatric symptoms during the course of SSc has not been evaluated yet with standardized evaluation scales, and an important breakthrough can be made in understanding the underlying mechanisms of psychiatric manifestations, in order to improve therapeutic management and quality of life.

Adaptation, Psychological↗
PubMed2002

[Long-term treatments for systemic sclerosis: what are the perspectives?].

Systemic sclerosis (SSc) is responsible for fibrosis of the dermis and other organs as well as vascular abnormalities. While the pathogenesis of SSc is continually being better understood, there is still no single therapeutic agent that has been shown to increase survival in a prospective randomized trial. Traditional medications such as colchicine and D-penicillamine are disappointing in clinical practice, and the latter one failed to clearly show benefit when tested in a prospective placebo controlled trial comparing conventional high dose versus low dose. Conversely, new disease modifying agents are emerging such as cyclophosphamide (CYC) in interstitial pulmonary disease and stem cell autograft after high dose CYC therapy in patients who develop visceral involvement in the three first years of evolution of the disease. Organ specific therapy may show dramatic benefit, such as angiotensin converting enzyme inhibitors in renal crisis and epoprostenol in primary pulmonary hypertension. We will try to review disease modifying agents available in SSc and emphasize new therapeutic agents that are currently being evaluated, including vasodilators, anti-inflammatory, anti-fibrosing agents and immunosuppressive molecules.

Angiotensin-Converting Enzyme Inhibitors↗
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↗
PubMed2002

Giardia lamblia infection in a patient with myotonic dystrophy.

Myotonic dystrophy is an autosomal dominant muscle disorder characterized by muscle wasting and weakness and a number of other systemic abnormalities. Some patients have hypo-IgG that is asymptomatic in most of them. We report the case of a 42-year-old woman with myotonic dystrophy and hypo-IgG who experienced asthenia and weight loss secondary to Giardia lamblia bowel infection.

Adult↗