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Biomedical subjects

L Mouthon

Publications and source records attributed to L Mouthon.

At least 73 records · Page 4Linked to original sources
PubMed1999

Localized subcutaneous Nocardia farcinica abscess in a woman with overlap syndrome between systemic scleroderma and polymyositis.

Nocardia farcinica is an increasingly common cause of human infection in Europe. We observed an isolated nodular subcutaneous abscess due to N. farcinica in the forearm of a young patient with overlap syndrome between systemic sclerosis and polymyositis. Despite in vitro resistance to trimethoprim-sulfamethoxazole, this oral combination completely resolved the lesion within 3 weeks and was maintained for 6 months. The spectrum of cutaneous nocardiosis in the immunocompromised host is discussed.

Abscess↗
PubMed1998

Self-reactive antibodies (natural autoantibodies) in healthy individuals.

Antibodies that are present in the serum of healthy individuals in the absence of deliberate immunization with any antigen, are refered to as natural antibodies. A vast majority of natural antibodies react with one or more self antigens and are termed as natural autoantibodies. The importance of natural autoantibodies in immune regulation has long been neglected, since tolerance to self was thought to be primarily dependent on the deletion of autoreactive clones, rather than on peripheral suppressive mechanisms. Clonal deletion and energy cannot account, however, for the prevalence of natural autoreactivity among healthy individuals. It is now well established that autoreactive antibodies and B cells, and autoreactive T cells, are present in healthy individuals, and in virtually all vertebrate species. Autoreactive repertoires are predominantly selected early in ontogeny. Questions pertaining to the role of natural antibodies in the regulation of the immune response and maintenance of immune homeostasis and to the distinction between natural autoreactivity and pathological autoimmunity have not been adequately addressed. Here, we focus on the current knowledge on the physicochemical and functional properties of NAA in man, and the use of NAA for therapeutic intervention. reserved.

Autoantibodies↗
PubMed1998

Selective impairment of serum antibody repertoires toward muscle and thymus antigens in patients with seronegative and seropositive myasthenia gravis.

We analyzed the antibody (Ab) repertoires of IgM and IgG of patients with seropositive and patients with seronegative myasthenia gravis (MG) toward self antigens by means of a quantitative immunoblotting technique using normal human tissue extracts as sources of self antigens. Repertoires of reactivities of IgG and IgM with liver, kidney and stomach antigens were conserved between myasthenic patients and controls. IgG and IgM Ab repertoires toward muscle antigens differed significantly between patients with seropositive MG and healthy donors, as assessed by multiparametric statistical analysis. Patterns of Ab reactivities to muscle antigens were similar in patients with seronegative MG and healthy controls. Antibody repertoires of IgG and IgM toward thymus antigens of both seropositive and seronegative MG patients, differed significantly from those of healthy individuals. Our results indicate that MG is characterized by a selective impairment of self-reactive Ab repertoires toward muscle and thymus antigens. The observation that self-reactive Ab repertoires toward thymus antigens are similar in patients with seropositive and seronegative MG suggests that both forms of MG share common immunopathological features.

Adult↗
PubMed1998

Analysis of self-reactive antibody repertoires in normal pregnancy.

We analysed the reactivities of IgM and of IgG towards protein antigens in normal human tissue extracts in the sera of healthy women in the third trimester of pregnancy, young nulliparous women and adult men. The self-reactive antibody repertoires of IgM in the serum of pregnant women exhibited striking homogeneity among individuals and did not differ from those of nulliparous women and young males. Similar results were obtained upon analysis of repertoires of IgG purified from serum. Multiparametric statistics failed to discriminate among pregnant women, nulliparous women and young adult males for reactivity of serum IgG and purified IgG with self-antigens. The results indicate that self-reactive IgM and IgG repertoires do not differ in the third trimester of a normal pregnancy from those which characterize healthy adults.

Adult↗
PubMed1997

Instability of natural antibody repertoires in systemic lupus erythematosus patients, revealed by multiparametric analysis of serum antibody reactivities.

Recent views on autoimmune diseases invoke generalized but specific perturbations in antibody repertoires, rather than the clonally restricted or non-specific polyclonal alterations proposed thus far. The present experiments analyse serum antibody reactivities in 24 systemic lupus erythematosus (SLE) patients and 17 healthy controls, using a method that quantitatively scores a large number of antibody reactivities and allows for multiparametric statistical analyses. The results show global but relatively specific perturbations in SLE antibody repertoires, and identify novel disease-associated reactivity patterns. Furthermore, a time series analysis of serum antibodies over 3 months demonstrates instability of natural antibody repertoires in individual SLE patients, contrasting with their remarkable conservation in healthy donors. Moreover, the method used clusters controls and patients independently, and might prove of diagnostic value, once large data bases are established.

Adolescent↗
PubMed1997

Analysis of antibody reactivities toward self antigens of IgM of patients with Waldenström's macroglobulinemia.

By using a quantitative immunoblotting technique, we have analyzed the repertoires of antibody reactivities of IgM directed toward self antigens in the serum of patients with Waldenström's macroglobulinemia (WM) and in the serum of healthy adults. Monoclonal IgM of patients with WM expressed various degrees of polyreactivity and a high degree of heterogeneity with regard to the number and the nature of the protein bands that were recognized in homologous tissue extracts. Heterogeneous patterns of reactivity of WM IgM contrasted with the conserved profiles of reactivity of IgM in the serum of healthy blood donors. Protein bands that were recognized by WM IgM belonged to the restricted set of self antigens recognized in homologous tissues by normal polyclonal IgM, indicating the absence of a disease-specific reactivity profile of monoclonal WM IgM. Thus, monoclonal IgM that is present in large amounts in WM distorts the homogeneous pattern of reactivity of natural antibodies with self antigens which characterizes the natural antibody repertoire of healthy individuals.

Adult↗
PubMed1996

The self-reactive antibody repertoire of normal human serum IgM is acquired in early childhood and remains conserved throughout life.

The authors have used a quantitative immunoblotting technique to analyse the antibody repertoire of IgM in cord blood and in the serum of young children, young adult males and aged males directed towards antigens in homologous tissues utilized as sources of self antigens. The reactivities of IgM with self antigens exhibited striking homogeneity and invariance among newborns. Self-reactive IgM repertoires of children, young adults and aged males were markedly conserved among individuals and comprised most of the anti-self reactivities that prevailed in neonates. Reactivities of IgM with bacterial antigens showed a high degree of homogeneity among newborns but were more diverse in children, young adults and elderly individuals. Diversity of IgM reactivities with self and non-self antigens did not vary significantly with aging. Principal component analysis (PCA) and linear discriminant analysis (LDA) of the data discriminated between self-reactive IgM repertoires of newborns and children, but failed to discriminate between repertoires of children, young adults and aged males. The data indicate that the self-reactive antibody repertoire of IgM differentiates during the first years of life and remains relatively constant thereafter.

Adult↗
PubMed1996

Mechanisms of action of intravenous immune globulin in immune-mediated diseases.

Intravenous immune globulin (IVIG) exhibits a number of immunomodulatory properties that are mediated by the Fe portion of IgG and by the spectrum of variable (V) regions contained in the immune globulin preparations. Five predominant and non-exclusive mechanisms of action have been proposed to account for the immunomodulatory effects of IVIG in immune-mediated diseases: (i) functional blockade of Fc receptors on splenic macrophages; (ii) inhibition of complement-mediated damage, an effect that is dependent on the ability of IgG to bind C3b and C4b and thus reduce the number of activated complement fragments that may deposit on target surfaces of complement activation; (iii) modulation of the production of cytokines and cytokine antagonists; (iv) neutralization of circulating autoantibodies by complementary (e.g. anti-idiotypic) antibodies in IVIG, a mechanism that accounts for the rapid decrease in titre of circulating autoantibodies that is often observed within hours following the infusion of IVIG; (v) selection of immune repertoires, a complex set of effects that may be observed in individuals receiving IVIG far beyond the half-life of the infused immunoglobulin and that is directly relevant to the ability of IVIG to, for example, suppress autoantibody-producing clones in patients with antibody-mediated autoimmune disease and modulate graft versus host disease (GVHD). IVIG has been shown to downregulate or activate B-cell clones expressing surface IgG that is complementary (anti-idiotypic) to V regions of antibodies present in IVIG. IVIG has been shown also to interact with surface molecules of T cells that are essential to immune regulation, such as the alpha beta TCR, CD5, CD4, non-polymorphic determinants of MHC class I molecules and adhesion molecules of T and B cells. The complex interactions of IVIG with functional molecules of cells of the immune system are relevant to its therapeutic effects in T cell- as well as B cell-mediated diseases and indeed, to our understanding of the physiological role of normal IgG and antibody networks in controlling autoreactivity in healthy individuals.

Adjuvants, Immunologic↗
PubMed1995

Analysis of the normal human IgG antibody repertoire. Evidence that IgG autoantibodies of healthy adults recognize a limited and conserved set of protein antigens in homologous tissues.

We have used a quantitative immunoblot technique to analyze the Ab repertoire of IgG in the serum of healthy adults with a large panel of homologous and foreign Ags in tissue extracts. Densitometric patterns of reactivity of purified IgG with self-Ags exhibited striking homogeneity among individuals with regard to the protein bands that were recognized. Purified IgG showed higher levels of reactivity with self-Ags than IgG in whole serum. Reactivity with self-Ags of IgG in whole serum was restricted to a small number of protein bands (fewer than 10). There were significant inter-individual differences in the intensity and nature of immunoreactivities. Purified IgG of different individuals exhibited heterogeneous patterns of immunoreactivity with Ags in bacterial extracts. Comparative analysis of repertoires of IgG and IgM indicated that all protein Ags recognized by IgM were also reactive with purified IgG. Some proteins in homologous and in foreign tissue extracts reacted solely with IgG. Our observations provide direct evidence for the restricted and conserved character of the antiself-repertoire of IgG of healthy adults and suggest that natural IgG Ab repertoires in serum are specifically selected for reactivity with a limited set of self-Ags. In addition, IgG autoreactivity in whole serum is controlled by non-IgG factors that determine the unique reactivity pattern of each individual.

Adult↗
PubMed1995

Invariance and restriction toward a limited set of self-antigens characterize neonatal IgM antibody repertoires and prevail in autoreactive repertoires of healthy adults.

Analysis of the reactivity of IgM with self-antigens in tissues by a quantitative immunoblotting technique showed striking invariance among newborns in the human and in the mouse. The self-reactive repertoire of IgM of adults was also markedly conserved; it comprised most anti-self reactivities that prevailed among neonates. Multivariate analysis confirmed the homogeneity of IgM repertoires of neonates toward self- and non-self-antigens. Multivariate analysis discriminated between newborn and adult repertoires for reactivity with two of five sources of self-proteins and with non-self-antigens. Our observations support the concept that naturally activated B lymphocytes are selected early in development and throughout life for reactivity with a restricted set of self-antigens.

Adult↗
PubMed1995

Analysis of the natural human IgG antibody repertoire: life-long stability of reactivities towards self antigens contrasts with age-dependent diversification of reactivities against bacterial antigens.

We used a quantitative immunoblotting technique to analyze the repertoires of IgG antibody reactivities in the serum of healthy young children, young adult males and aged males with self and non-self antigens. Densitometric patterns of reactivity of purified IgG with self antigens were highly conserved between individuals within a given age group and across age groups. Inter-individual differences were observed, however, upon analysis of self reactivities of IgG in whole serum. A striking heterogeneity between individuals within a given age group and across age groups characterized the reactivity of purified IgG and of IgG in whole serum with bacterial antigens. Inter-individual differences were more marked among aged individuals than among individuals of other age groups. Analysis of variances of reactivities of IgG with bacterial antigens further demonstrated an increased diversity of repertoires of aged donors compared with those of young adults and children. Our results document the stability of the self-reactive repertoires of IgG throughout life, which contrasts with the diversification of the repertoire of IgG antibody reactivities directed toward foreign antigens with aging. These findings support the concept that self-reactive antibody repertoires are positively selected throughout life by a restricted set of self antigens shared by all individuals.

Adult↗
PubMed1995

Hepatitis B virus-related polyarteritis nodosa and membranous nephropathy.

We report the case of man with a history of post-transfusion chronic persistent hepatitis due to hepatitis B virus (HBV), who secondarily developed polyarteritis nodosa (PN) and membranous nephropathy (MN) simultaneously. At that time, liver biopsy yielded the diagnosis of active chronic hepatitis, and serological tests showed a high replication rate of HBV. PN was due to HBV infection, but the etiology of MN was uncertain, as it has never been described in PN, even in its microscopic form. There was no evidence of paraneoplastic syndrome or other causes of MN. Although the renal biopsy did not give any indication of HBV-related glomerulonephritis, the patient was considered to have an association of classic PN and MN, both related to HBV. Treatment combined plasmapheresis and interferon-alpha.

Aged↗
PubMed1994

Immune modulating effects of intravenous immunoglobulin (IVIg) in autoimmune diseases.

Administration of intravenous immunoglobulins (IVIg) have now been reported to be beneficial in a large number of autoimmune diseases, whether mediated by autoantibodies or by T cells. We have proposed that the immunoregulatory effect of IVIg in autoimmune diseases is dependent on the selection of recipient's immune repertoires by variable (V) regions of infused immunoglobulins. Thus: (a) IVIg contains antibodies reactive with idiotypes of natural and disease-related autoantibodies and surface immunoglobulins of B cells; IVIg also contains antibodies reactive with idiotype, framework and constant regions of the beta chain of the alpha beta T cell receptor; (b) infusion of IVIg results in transient or long-lasting suppression of specific autoantibody clones in vivo and in stimulation of a distinct subset of B cells reactive with F(ab')2 fragments of IVIg; (c) infusion of IVIg alters the general "architecture" of the network as assessed by studying the kinetic patterns of spontaneous fluctuations of natural autoantibodies in serum; (d) infusion of normal mouse Ig in healthy adult mice selects expressed immune repertoire by removing late pre-B and B cells in the bone marrow, mostly those expressing D proximal VH genes, and by activating distinct subsets of B cells and CD4+ T cells in the spleen; and (e) infusion of IVIg results in a modulation of synthesis and release of cytokines. Although dependent on the V-region reactivities (composition) or injected preparations, these effects probably also require that the infused immunoglobulin contains an intact Fc moiety. This review focuses on autoimmune and inflammatory diseases in which IVIg therapy has been beneficial. Recent recommendations from a committee of experts for IVIg therapy have been pointed out.

Adjuvants, Immunologic↗
PubMed1993

[Mechanisms of action of intravenous immunoglobulins in the treatment of autoimmune diseases].

Administration of intravenous immunoglobulins (IVIg) has been reported to be beneficial in a large number of autoimmune diseases, whether mediated by autoantibodies or by T cells. Immunoregulatory effect of IVIg in autoimmune diseases is dependent on the interaction of the Fc portion of IVIg with Fc receptor on leukocytes and on the selection of recipient's immune repertoires by variable (V) regions of infused immunoglobulins. Thus: a) IVIg contains antibodies reactive with idiotypes of natural and disease-related autoantibodies and surface immunoglobulins of B cells; IVIg also contains antibodies reactive with idiotype, framework and constant regions of the beta chain of the T cell receptor; b) infusion of IVIg results in transient or long lasting suppression of specific autoantibody clones in vivo; c) infusion of IVIg alters the general "architecture" of the network as assessed by studying the kinetic patterns of spontaneous fluctuations of natural autoantibodies in serum; d) infusion of IVIg results in a modulation of synthesis and release of cytokines. This review points out mechanisms of action of IVIg in autoimmune and inflammatory diseases, focussing on those depending on V region of infused immunoglobulins.

Animals↗