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L Mouthon

Publications and source records attributed to L Mouthon.

At least 55 records · Page 3Linked to original sources
PubMed2000

Analysis of human self-reactive antibody repertoires by quantitative immunoblotting.

We review the use of a quantitative immunoblotting technique to characterize human self-reactive antibody repertoires in health and disease. The interactions of plasma IgM and IgG with tissue extracts as sources of self-antigens were analyzed by quantitative immunoblotting. Data were compared by means of multiparametric statistical analysis. The data summarized here demonstrate that natural self-reactive antibody repertoires of healthy individuals are restricted to a limited subset of immunodominant autoantigens that is selected early in development, and remains conserved between individuals through ageing. The selection of human natural self-reactive IgG antibody repertoires requires normal T-/B-cell interactions. The immunoblotting assay has the potential to distinguish between autoimmune diseases with organ-related oligoclonal expansion of self-reactive clones and those characterized by broad alterations of immunoregulation. However, organ-specific autoimmune diseases may be characterized by altered patterns of antibody repertoires unrelated to the target organ. The assay also revealed an unexpected defect in the regulatory function of self-reactive IgM on the expression of self-reactive IgG repertoires in several systemic and organ-specific autoimmune diseases. The results are discussed in the light of our current understanding of the processes of selection of self-reactive B-cells and the pathophysiology of autoimmunity.

Autoantibodies↗
PubMed2000

Altered control of self-reactive IgG by autologous IgM in patients with warm autoimmune hemolytic anemia.

Warm autoimmune hemolytic anemia (WAIHA) is characterized by an accelerated clearance of red blood cells (RBCs) associated with the presence of anti-RBC immunoglobulin (Ig)G autoantibodies. In the present study, we analyzed the self-reactive IgG and IgM antibody repertoires of patients with WAIHA using a technique of quantitative immunoblotting on a panel of whole tissue extracts as sources of self-antigens. Data were compared by means of multiparametric statistical analysis. We demonstrate that self-reactive antibody repertoires of IgG purified from plasma and of IgG purified from RBC eluates do not differ between healthy donors and patients with WAIHA, whereas autoreactive repertoires of IgM from patients exhibit broadly altered patterns of reactivity as compared with those of healthy controls. We further demonstrate that IgG purified from eluates of RBCs of healthy donors induces agglutination of RBCs in an indirect Coombs assay to a similar extent as IgG purified from eluates of RBCs of patients with WAIHA. The capability of IgG to induce agglutination of RBCs is suppressed in unfractionated eluates of healthy donors' cells, whereas it is readily found in unfractionated eluates of patients' RBCs. IgM is an essential factor in controlling the ability of IgG in unfractionated RBC eluates to induce agglutination of RBCs. These observations indicate that anti-RBC IgG autoantibodies of patients with WAIHA share extensive similarity with natural antiRBC autoantibodies of healthy donors and suggest that defective control of IgG autoreactivity by autologous IgM is an underlying mechanism for autoimmune hemolysis in WAIHA. (Blood. 2000;95:328-335)

Adult↗
PubMed2000

Successful treatment of thymoma-associated pure red cell aplasia with intravenous immunoglobulins.

Repeated cycles of intravenous immunoglobulins (IVIG) have been reported to be successful in a few patients with idiopathic pure red cell aplasia (PRCA) or associated with another pathology. The efficacy of this treatment for PRCA with thymoma has not been reported previously. We describe here the case of a 75-yr-old man who presented with PRCA associated with a benign thymoma. After failure of thymectomy, corticosteroids and octreotide, a complete durable remission was obtained after a single 5-d cycle of IVIG.

Adrenal Cortex Hormones↗
PubMed2000

[Intravenous immunoglobulins: anti-infection indications].

Intravenous immunoglobulin (IVIg) are therapeutic preparations of intact IgG that are obtained from a pool of more than one thousand healthy blood donors and contain antibodies directed toward a large panel of microbial agents. IVIg contain high amounts of antibodies with opsonising activity and are indicated in substitutive treatment of patients with constitutive hypogammaglobulinemia. IVIg also contain antibodies able to neutralize certain bacterial toxins exerting superantigenic activity, and by this mechanism exert both anti-infectious and immunomodulating activity. During the last fifteen years, indications of IVIg in the prophylactic treatment of infections have been well defined: a) primary antibody deficiency; b) multiple myeloma and chronic lymphocytic leukemia with hypogammaglobulinemia and recurrent bacterial infections; c) bone marrow allograft; d) childhood AIDS; e) chicken pox seroprophylaxis in immunosuppressed patients and pregnant women. Therapeutic indications of IVIg in infectious diseases are limited to chronic parvovirus B19 infection associated or not with HIV infection. Other therapeutic indications are not well defined.

Bacterial Infections↗
PubMed2000

[Immunomodulatory effects of intravenous immunoglobulins].

Intravenous immunoglobulin (IVIg) has been used for many years in the treatment of primary and secondary antibody deficiencies. IVIg was first demonstrated to be effective in auto-immune desorders twenty years ago in the treatment of idiopathic thrombocytopenic purpura. The beneficial effect of IVIg has since been established in the Guillain-Barré syndrome, chronic inflammatory demenilating polyneuropathy, myasthenia gravis, dermatomyositis, Kawasaki syndrome and graft versus host disease. The beneficial effect of IVIg has been suggested in a large number of other auto-immune and systemic inflammatory conditions. The mode of action of IVIg is complex, involving Fc receptor blockade, interference with complement activation and the cytokine network, provision of anti-idiotypic antibodies and modulation of T and B cell activation and differentiation. Such a broad range of activities reflects the function of normal circulating immunoglobulins in maintaining tolerance to self in healthy individuals.

Adjuvants, Immunologic↗
PubMed2000

Brachial plexopathy associated with diffuse edematous scleroderma.

Peripheral nervous system (PNS) involvement is rare in systemic sclerosis (SSc), usually restricted to peripheral nerve entrapment. To our knowledge, only one case of scleroderma with brachial plexus involvement has been reported previously. We report here on a 61-year-old woman with past history of limited cutaneous SSc who developed motor deficiency in the left arm concomitant with diffuse edematous scleroderma without evidence for trauma or compression of the brachial plexus. After six months intravenous pulse cyclophosphamide therapy, dramatic improvement of skin and neurological involvement was observed.

Anti-Inflammatory Agents↗
PubMed2000

Favorable outcome of gemcitabine-induced respiratory distress syndrome.

Gemcitabine, a deoxycytidine analog, is used to treat solid tumors, like non-small-cell lung carcinoma. The most commonly reported adverse effects are reversible and generally not fatal. However, among the five cases of acute respiratory distress syndrome (ARDS) secondary to gemcitabine treatment reported since 1997, four were fatal despite corticosteroid therapy. We describe here a patient who received gemcitabine for bronchial epidermoid carcinoma and developed ARDS which spontaneously regressed after gemcitabine withdrawal.

Aged↗
PubMed1999

Defective self-reactive antibody repertoire of serum IgM in patients with hyper-IgM syndrome.

We have analyzed the self-reactive repertoires of IgM and IgG Abs in the serum of 19 patients with hyper-IgM syndrome (HIM) by means of a quantitative immunoblotting technique that allows for a quantitative comparison of Ab repertoires in health and disease by multiparametric statistical analysis. Normal tissue extracts of liver, lung, stomach, and kidney were used as sources of self Ags. Extracts of Pseudomonas aeruginosa and Staphylococcus epidermidis were used as sources of nonself Ags. We demonstrate a significant bias in repertoires of reactivities of IgM of patients with HIM with self Ags. Ab repertoires of IgM toward nonself Ags did not differ, however, between patients and controls. No difference was found between IgM repertoires of untreated patients and those of patients receiving substitutive treatment with i.v. IgG. IgG in the serum of HIM patients lacked reactivity with self Ags, although it exhibited a pattern of reactivity with nonself Ags that was similar to that of IgG of healthy controls. The data demonstrate that functional CD40-CD40 ligand interactions are essential for the selection of natural self-reactive B cell repertoires.

Adolescent↗
PubMed1999

[Immunomodulatory effects of intravenous immunoglobulins in autoimmune diseases].

PURPOSE: Intravenous immunoglobulins (IVIg) therapy has been reported to be beneficial in a large number of autoantibody-mediated or self-reactive T cells-associated autoimmune diseases. Thus, the beneficial effect of IVIg is probably due to multiple distinct mechanisms. MAIN POINTS: The immunoregulatory effect of IVIg in autoimmune diseases is dependent on: interaction of the Fc portion of IVIg with Fc receptors on leucocyte surfaces; interaction of infused IgG with complement components; modulation of synthesis and release of cytokines produced by lymphocytes and monocytes: V region-dependent neutralization of circulating autoantibodies by infused IgG; selection of immune repertoires; modulation of cell proliferation, particularly through modulation of Fas-induced apoptosis; interaction of IVIg with numerous other molecules onto the surface of T and B cells. PERSPECTIVES: Better understanding of these mechanisms should allow a better definition of the spectrum of diseases likely to benefit from IVIg treatment.

Apoptosis↗
PubMed1999

[Treatment of ANCA-positive systemic vasculitis with intravenous immunoglobins].

PURPOSE: ANCA positive systemic vasculitis comprises Wegener granulomatosis (WG), microscopic polyangiitis (MPA) and Churg Strauss syndrome (CSS). In WG, anti-Pr3 ANCA are present in 90% of the cases, whereas in MPA and CSS ANCA are present in 40 to 80% and 25 to 60% of the cases, respectively, with anti-MPO specificity. The treatment of WG and MPA associates prednisone and cyclophosphamide, and clinical remission is obtained in 70 to 90% of the cases. However, relapses occur in 10 to 30% of the patients and tolerance of corticosteroids and immunosuppressive therapy is not always good. STATE OF THE ART: Intravenous immunoglobulins (IVIg) are well tolerated and indicated in a large number of autoimmune and systemic inflammatory diseases. In vitro IVIg specifically inhibit ANCA activity through V-region dependent interaction of anti-ANCA anti-idiotypic antibodies with ANCA. Several open studies and a few case reports of patients with WG or MPA treated with IVIg were published in the past seven years, with various results. PROJECTS: A prospective controlled multicenter study is necessary to evaluate the efficacy of IVIg in the treatment of ANCA positive vasculitides.

Anti-Inflammatory Agents↗
PubMed1999

Stability of natural self-reactive antibody repertoires during aging.

We have used a quantitative immunoblotting technique to analyze the repertoires of self-reactive antibodies in serum samples obtained from the same five healthy adults over a 25-year interval. The average age of the donors was 43 years at the time of the first serum sample and 69 years at the time of the second serum sample. The antibody repertoires of IgM and IgG were found to be strikingly similar among individuals in both early and late samples. Densitometric profiles of self-reactivity of serum IgM and of purified serum IgG remained unchanged over the 25-year interval. The total reactivity of serum IgG decreased significantly over the 25-year period. The observed stability of the natural self-reactive IgM and IgG antibody repertoires with aging supports the view that autoreactive B cells in the normal immune system are positively selected for reactivity with a limited set of immunodominant self-antigens throughout life.

Adult↗
PubMed1999

[Periarteritis nodosa induced by hepatitis B virus].

Polyarteritis nodosa (PAN) induced by the hepatitis B virus (HBV) is a rare condition whose incidence has decreased markedly over the last decade. HBV-related PAN is an acute condition that occurs within six months of HVB infection and shares many features with classic PAN. Some manifestations, however, are more common in HBV-related PAN, such as abdominal signs, renal failure, malignant arterial hypertension, and orchitis. Tests for antineutrophil cytoplasmic antibody are usually negative. Management combines a short course of steroid therapy, plasma exchanges, and antiviral drugs. The ten-year disease-free survival rate is 80%. Over half the patients develop antibody to Hbe and 24.4% to HBs.

Chronic Disease↗
PubMed1999

IgA glomerulonephritis associated with microscopic polyangiitis or Churg-Strauss syndrome.

When renal insufficiency occurs in classical antineutrophil cytoplasm antibody- (ANCA) associated vasculitides, histological examination usually finds pauci-immune focal segmental glomerulonephritis. We report on 2 cases of histologically proven necrotizing vasculitis associated with IgA nephropathy. Concomitant vasculitis and IgA nephropathy has only rarely been reported but this joint occurrence may not be coincidental as its pathophysiology is not known. Among vasculitides, IgA nephropathy has more frequently been associated with Henoch-Schoenlein purpura: one microscopic polyangiitis unusual because the patient simultaneously presented ANCA and microaneurysms, and the other Churg-Strauss syndrome associated with mild renal insufficiency. This uncommon association might represent a possible overlap syndrome between these ANCA-associated vasculitides and IgA nephropathy or simply a new type of glomerulonephritis that must be taken into account in these vasculitides.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1999

[Common variable immunodeficiency: one or multiple illnesses? 3 clinical cases].

Common variable immunodeficiency (CVID) is a major antibody-deficiency syndrome, associated with increased risk of bacterial infection, as well as autoimmune and granulomatous disease. The clinical and immunological features are heterogeneous. This heterogeneity is expressed by the case reports of three selected patients. These observations will be discussed, with reference to a recent classification of CVID distinguishing four different clinical entities: i) CVID presenting with clinical and immunological features of X-linked agammaglobulinemia; ii) CVID presenting with clinical and immunological features of X-linked hyper-IgM syndrome; iii) CVID associated with systemic granulomatous disease; and iiii) CVID associated with autoimmune manifestations.

Adult↗
PubMed1999

Concomitant polymyositis and myasthenia gravis reveal malignant thymoma. A case report and review of the literature.

The frequency of thymona associated with autoimmune diseases has been reported to be increased, with 50% of thymoma patients also having myasthenia gravis (MG). Other autoimmune disorders, such as autoimmune erythroblastopenia and polymyositis (PM), have been less frequently associated with thymoma. The association of MG and PM with thymoma is rare. We here report the case of a 66-year-old woman whose concomitant MG and PM revealed malignant thymoma and review the other published cases of this association.

Aged↗