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Biomedical subjects

L Mouthon

Publications and source records attributed to L Mouthon.

At least 19 recordsLinked to original sources

Severe perturbations of the blood T cell repertoire in polymyositis, but not dermatomyositis patients.

Polymyositis and dermatomyositis are diseases characterized by muscle weakness and muscle inflammatory infiltrates. Their pathogenesis remains unclear. A central role for endomysial autoaggressive CD8(+) T cells is suspected in polymyositis and for perivascular B cells in dermatomyositis. We compared the T cell repertoire of 10 polymyositis and 10 dermatomyositis patients by immunoscope, a method providing a global assessment of the T cell repertoire and a sensitive detection of clonal T cell expansions. Samples were analyzed qualitatively and quantitatively in the blood (unsorted cells and CD4(+) and CD8(+) cells) and in muscle infiltrates. Dramatic perturbations of the T cell repertoire were observed in the blood of polymyositis but not dermatomyositis patients (p < 0.0005), the latter being undistinguishable from controls. These perturbations were due to oligoclonal expansions of CD8(+) T cells and most blood clonal expansions were also found in muscle. These results indicate that the pathogenesis of polymyositis and dermatomyositis is different and reinforce the view that polymyositis but not dermatomyositis is an autoimmune CD8(+) T cell-mediated disease. Moreover, this method may be helpful for the differential diagnosis of polymyositis and dermatomyositis and for noninvasive follow-up of polymyositis patients.

Adult↗

Breast adenocarcinoma complicating Kallmann's syndrome.

Carcinoma of the breast is relatively rare among men, accounting for less than 1% of all malignancies. An increased risk has been associated with benign breast diseases, such as gynecomastia, Klinefelter's syndrome, testicular disorders, exogenous estrogen use, radiation, or a family history of male or female breast cancer. To date, hypogonadotrophic hypogonadism has never been associated with male breast cancer. We report here the first case of breast cancer coexisting with Kallmann's syndrome in a 66-year-old man.

Journal Article↗

Treating systemic sclerosis in 2001.

Systemic sclerosis (SS) is characterized by sclerosis of the dermis and internal organs and by vascular abnormalities. Although the pathophysiology of the disease has been partly elucidated, the efficacy of long-term treatments remains limited, with no significant increase in survival in prospective studies. Conventional drug treatments are disappointing in clinical practice, and in a recent prospective randomized study standard-dose D-penicillamine was not more effective than mini-dose D-penicillamine. New long-term treatments are emerging for diffuse SS, including cyclophosphamide for patients with progressive interstitial lung disease or stem cell transplantation for those with early organ involvement. The most effective treatments remain symptomatic, such as angiotensin-converting enzyme inhibitors for acute renal crisis, calcium channel antagonists for Raynaud's phenomenon, and proton pump inhibitors for the complications of gastroesophageal reflux. This review article focuses on long-term treatments that are most likely to be effective and suggests symptomatic treatment strategies tailored to specific organ involvements.

Antineoplastic Agents↗

Polyarteritis nodosa and mixed cryoglobulinaemia related to hepatitis B and C virus coinfection.

OBJECTIVE: To determine the responsibility of hepatitis B virus (HBV) and hepatitis C virus (HCV) and therapeutic implications in a patient who developed systemic vasculitis. CASE REPORT: The case of a 38 year old woman who had a past history of addiction to intravenous drugs and developed systemic vasculitis after infection by HBV and HCV is described. The clinical and laboratory findings substantiated not only the diagnosis of polyarteritis nodosa (PAN) but also that of mixed cryoglobulinaemia with a monoclonal IgMkappa component. CONCLUSION: Because cryoglobulins are rarely found in HBV related PAN but often associated with HCV infection, and in light of the histological findings, cryoglobulinaemia was interpreted as being secondary to HCV infection. This example of a highly complex situation emphasises the need to gather all relevant clinical, biological, histological, and complementary data so that the best treatment for overlapping of distinct vasculitides can be selected.

Adult↗

Risk factors and prognostic influence of infection in a single cohort of 87 adults with systemic lupus erythematosus.

OBJECTIVES: To describe infectious complications and analyse their risk factors and prognostic role in adults with systemic lupus erythematosus (SLE). METHODS: A monocentric cohort of 87 adults with SLE (1960-1997) was studied to determine the risk factors for infection (disease activity evaluated by SLAM and SLEDAI scores, type of organ(s) involved or any biological abnormality, specific treatments) by comparing patients who had suffered at least one infectious episode (n=35; 40%) with non-infected patients (n=52; 60%). Prognostic indicators were assessed by comparing survivors at 10 years with non-survivors. RESULTS: Of the 57 infectious episodes, 47 (82%) were of bacterial origin, 16 (28%) were pneumonia, and 46 (81%) were community acquired. According to univariate analysis, significant risk factors for infection were: severe flares, lupus glomerulonephritis, oral or intravenous corticosteroids, pulse cyclophosphamide, and/or plasmapheresis. No predictors were identified at the time of SLE diagnosis. Multivariate analyses retained intravenous corticosteroids (p<0.001) and/or immunosuppressants (p<0.01) as independent risk factors for infection, which was the only factor for death after 10 years of evolution (p<0.001). CONCLUSION: In adults with SLE, infections are common and most often caused by community acquired bacteria. Intravenous corticosteroids and immunosuppressants are independent risk factors for infection, which is the only independent risk factor for death after 10 years of SLE evolution.

Adolescent↗

Localized neurological necrotizing vasculitides. Three cases with isolated mononeuritis multiplex.

Localized vasculitic neuropathies are increasingly reported. We describe 3 cases of peripheral neuropathy with necrotizing vasculitis confined to nerves and muscles without systemic involvement. These neuropathies were severe and relapsing, in contrast to a usually benign prognosis. Our cases appear to be isolated vasculitic neuropathies, with vasculitis strictly limited to the peripheral neuromuscular system without nonspecific clinical and/or biological systemic involvement.

Aged↗

Hydroxyethyl starch-induced renal insufficiency after plasma exchange in a patient with polymyositis and liver cirrhosis.

Hydroxyethyl starch (HES) is a macromolecular preparation that has been used as a volume expander since 1991. Renal toxicity of high-dose HES is now well recognized but potential renal toxicity of low-dose HES is poorly documented. Acute renal toxicity of cyclosporin A (CyA) may be responsible for osmotic nephrosis-like lesions. We report here the case of a 30-year-old male who developed cirrhosis due to hepatitis B and delta viruses and polymyositis. Polymyositis was treated with CyA, prednisone and plasma exchanges using low-dose HES as the replacement fluid. Renal insufficiency occurred with biopsy-proven osmotic nephrosis-like lesions, considered to be secondary to HES infusions and/or CyA.

Adult↗

Antigen inhalation as a triggering factor in systemic small-sized-vessel vasculitis. Four cases.

In order to identify small-sized-vessel vasculitis occurring immediately after massive inhalation of particles which could be considered antigenic, we performed a retrospective review of patients who consulted our Department of Internal Medicine between 1980 and 1998 and were diagnosed as having small-vessel vasculitis that developed immediately after massive exposure to inhaled particles. Four patients, 27 to 55 years old, presented with small-sized-vessel vasculitis (one with Wegener's granulomatosis and three with Churg-Strauss syndrome) which developed after massive inhalation of particles. Clinical manifestations occurred from a few hours to 10 days after inhalation of diesel fumes, cereal dust, flour or cereal dust and/or pigeon droppings. Three patients remain disease-free 8, 9 and 18 years after discontinuing treatment. One patient remains well after 3 years on low-dose corticosteroids and cyclophosphamide therapy. Our data suggest that primary antigens can cause small-sized-vessel vasculitides. Identifying such etiological factors could improve our understanding of the pathogenesis of systemic vasculitides and prevent relapses due to similar antigenic exposure.

Adult↗

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↗

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↗

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↗

[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↗

[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↗

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↗