[Iatrogenic angioedema due to estrogen, angiotensin conversion enzyme inhibitors, angiotensin receptor antagonists and dialysis membranes].
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Angioedema↗
Biomedical subjects
C Drouet
Publications and source records attributed to C Drouet.
[Sneddon syndrome with anti-mitochondrial type M5 antibodies].
INTRODUCTION: Antimitochondrial type M5 antibodies (AMA-M5) are among the immunological abnormalities associated with Sneddon syndrome. CASE: A 45 year-old woman, hospitalized for diplopia and with a 20-year history of obstetrical accidents, internuclear ophthalmoplegia and livedo, was diagnosed with Sneddon syndrome associated with primary antiphospholipid syndrome (APS) aggravated by the presence of AMA-M5. DISCUSSION: AMA-M5 are immunological markers of APS to the same extent as antiphospholipid antibodies. This case demonstrates the interest of screening for AMA-M5 in cases of strong clinical suspicion of APS when the anticoagulant lupus test is normal and no anti-cardiolipin, anti-b2 glycoprotein I or antiprothrombin antibodies are found.
Antiphospholipid Syndrome↗
Ion exchanges in apatites for biomedical application.
The modification of the composition of apatite materials can be made by several processes corresponding to ion exchange reactions which can conveniently be adapted to current coatings and ceramics and are an alternative to setting up of new synthesis methods. In addition to high temperature thermal treatments, which can partly or almost totally replace the monovalent OH- anion of stoichiometric hydroxyapatite by any halogen ion or carbonate, aqueous processes corresponding to dissolution-reprecipitation reactions have also been proposed and used. However, the most interesting possibilities are provided by aqueous ion exchange reactions involving nanocrystalline apatites. These apatites are characterised by the existence on the crystal surface of a hydrated layer of loosely bound mineral ions which can be easily exchanged in solution. This layer offers a possibility to trap mineral ions and possibly active molecules which can modify the apatite properties. Such processes are involved in mineralised tissues and could be used in biomaterials for the release of active mineral species.
Apatites↗
[Non-histaminic angiodema management: diagnostic and therapeutic interest of tranexamic acid].
INTRODUCTION: The diagnosis of chronic angioedema (localised and reversible oedema) is sometimes very difficult when there is no efficiency of anti-histaminics and corticosteroids. In these cases, bradykinin angioedema must be mentioned. Tranexamic acid is efficient and must be proposed. STUDY: We reported seven patients who have a non-histaminergic angioedema since an average of 8 years. Corticosteroids and histamine-1 blockers were not efficient. Daily tranexamic acid treatment (1 g x 3 per day) controlled the disease. Three patients had no more attack. The C1Inh antigen and function levels were normal. No secondary effect was described and all patients are still being treated (average of 20 months). CONCLUSION: When a non-histaminergic angioedema is suspected, tranexamic acid must be proposed as attack's treatment and as prophylactic treatment.
Adolescent↗
Angioedema and oral contraception.
BACKGROUND: Oral contraceptives can precipitate attacks of hereditary angioedema (ANE) or induce acquired forms. OBJECTIVE: We studied 5 patients who had an ANE which had begun under oral contraception and disappeared after stopping the pill. METHODS: We explored the clinical and biological characteristics of these patients. RESULTS: The symptoms developed during the first year or later after starting contraception; the patients reported relapsing swelling of the lips, hands, larynx and abdomen. All women had normal serum C4 and C1 inhibitor (C1Inh) antigen levels, but a lowered C1Inh activity, with a marked protein cleavage on the immunoblot. The suppression of the pill was associated with the regression of the edema and normalization of C1Inh function. CONCLUSION: The mechanism of these ANE is unknown. The could be due to a modulation of C1Inh expression upon androgens or an imbalance between coagulation proteins favoring C1Inh cleavage by its target proteases.
Adult↗
[Non-allergic angioedema: update].
PURPOSE: Nonallergic isolated angioedema is an uncommon clinical syndrome raising difficult diagnosis and therapeutic problems. Occurrences linked to a C1Inh are the predominant ones and have to be examined as a priority, taking into account the specificity of the associated follow-up. CURRENT KNOWLEDGE AND KEY POINTS: Diseases with a clinical profile close to hereditary angioneurotic edema, but without C1Inh anomaly, have been described recently. It is in fact family cases, concerning only women, where estrogens seem to play a dominant role. Angioedema's secondary aspects are gathering various pathologies (vasculitis, Gleich's syndrome, angioedema initiated by physical agents). The role played by some drugs must not be forgotten, mainly angiotensin converting enzyme inhibitors, which are at the origin of angiodema in nearly 0.5% of users. FUTURE PROSPECT AND PROJECTS: Uncontrolled activation of the contact system seems to play a major role in the main part of these angiodemas. The efficiency of the tranexaminic acid (which modulates its activation) is to be taken as evident. The key to the future seems to be the development of plasmin and bradykinin inhibitors.
Angioedema↗
Complement C4 monitoring in the follow-up of chronic hepatitis C treatment.
The overall role of complement in the host--pathogen relationship is now well understood. However, its involvement at a chronic stage of infection, such as chronic hepatitis C, is less well documented. Here, results are reported which point to the use of specific C4 monitoring in the follow-up of HCV patients. This study concerns 66 patients with chronic HCV infection, treated with interferon alpha 2b alone or with interferon alpha 2b + ribavirin, and 50 healthy adults as controls. Complement blood tests were performed to measure C1q, C3, C4, mannan binding lectin (MBL), C1s-C1 inhibitor complexes, total (CH50) and C4 (C4H) haemolytic activity; specific C4 activity was taken as the C4H/C4 protein ratio. Rheumatoid factor (RF) levels were also measured. A significant reduction in CH50 and specific C4 activity in HCV patients, compared with the healthy controls, was observed before the onset of treatment; the other parameters were not affected and no C1s-C1 inhibitor complexes were detected. At the same time, a significant reduction in specific C4 activity was observed in relapsers compared with sustained responders. These results point to a potential predictive function of C4 specific activity to monitor the response to therapy. Restoration of specific C4 activity at 6 months was better in responders than in non-responders. Complement activation in chronic hepatitis C does not seem to involve the C1 stage of the classical pathway. A negative correlation between specific C4 activity and RF titres suggests a possible involvement of RF in C4 activation, via the lectin pathway. Specific C4 monitoring appears to be a valuable tool for the follow-up of chronic hepatitis C treatment, together with the other conventional investigations.
Adult↗
Induction of thioredoxin by ultraviolet-A radiation prevents oxidative-mediated cell death in human skin fibroblasts.
The present study analyzes the expression of the thioredoxin/thioredoxin reductase (Trx/TR) system in UVA-irradiated human skin fibroblasts. Irradiation increases the intracellular level of Trx and a time-dependent increase of Trx mRNA is observed. Our data indicate that Trx translocates from the cytoplasm to the nucleus. In addition, UV exposure results in an increase in TR synthesis. In order to evaluate the function of Trx/TR system, we investigated the antioxidant role of Trx in transient transfected cells. The ROS accumulation in UVA irradiated cells was assessed using flow cytometry. A 3-fold decrease in ROS production was observed in transiently transfected fibroblasts. These results indicate that Trx acts as an antioxidant protein in UVA irradiated fibroblasts. As ROS are inducers of cell death, this raises the question as to whether Trx is able to protect cells from apoptosis and/or necrosis induced by UVA. Six hours after UVA-irradiation, 29.92% of cells were annexin-V positive. This population was significantly reduced in Trx-transfected cells (8.58%). Moreover, this work demonstrates that Trx prevents the loss of the membrane potential of the mitochondria, the depletion of cellular ATP content, and the loss of cell viability induced by irradiation.
Adenosine Triphosphate↗
Early lung leukocyte infiltration, HLA and adhesion molecule expression predict chronic rejection.
Obliterative bronchiolitis remains the main cause of graft dysfunction and death after 1 year. Defined by an irreversible airway obstruction, bronchiolitis obliterans syndrome is usually recognized in the advanced stage of the disease, with histological evidence of fibrotic damage. Fibrosis represents the end-stage of an inflammatory process, leading to the postulate that chronic lung graft dysfunction is preceded by cellular and molecular events. This study was performed during the first year following lung transplantation, in the absence of histological or functional criteria of chronic rejection. Transbronchial biopsies from eight lung allografts were examined. Four developed a bronchiolitis obliterans syndrome (Group I), and 4 had good outcomes (Group II) at 2 years. Using immunohistochemistry, the aim of the study was to correlate early immunological events with graft outcomes at 2 years. An up-regulation of HLA class I antigen (P = 0.0001), an overexpression of Ki-67 (P = 0.006) on bronchial epithelium, and graft infiltration by CD45+, CD25+ cells (P = 0.003) were significantly associated with the development of chronic rejection. An overexpression of numerous adhesion molecules was observed. However, only very late antigen-4 had a discriminative value (P = 0.04), preceding chronic graft dysfunction. Our results suggest that graft dysfunction is associated with early molecular and cellular events, and raises the possibility that a fibroproliferative disorder is initiated shortly after transplantation. The recognition of such early immunological markers might facilitate improved graft management and prognosis.
Adolescent↗
Chronic restraint stress induces severe disruption of the T-cell specific response to tetanus toxin vaccine.
Chronic stress is known to induce immunological disorders. In the present study we examined the consequences of chronic restraint stress on the immune response to tetanus toxin in mice. We investigated the repartition of subsets of lymphoid cells in blood and spleen, the functional ability of lymphocytes to proliferate and to produce cytokines, and antibody titres against tetanus toxin following stress. We report discordance of the stimulation index of lymphocytes in the restraint group: the proliferating rate severely decreased following stimulation with a relevant antigen, whereas it increased with mitogen. Thus, we report a decrease in cytokine production with relevant antigen (interferon-gamma and interleukin-10), without a T helper type 1 and 2 secretion imbalance. Moreover, we observed an alteration in the humoral response, including a delay in isotype maturation and an immunoglobulin G1/G2a imbalance.
Animals↗
[Acquired angioneurotic edema. Clinical and biological characteristics in 9 patients].
OBJECTIVE: Angioneurotic edema (AE) is a rare but severe disease. Hereditary AE is the more well-known form. The acquired form is exceptional: the symptoms are the same but there are some biologic and treatment differences. We investigated the clinical and biochemical features in nine patients with acquired angioneurotic edema (AAE). PATIENTS AND METHODS: Four of the patients with type I AAE presented an accelerated metabolism of C1Inh, associated with a hematology disease. Their C4, C1q and C1Inh plasma levels were low. Four patients had type II AAE associated with an autoantibody to C1Inh. Their C1Inh plasma levels were normal or low but the functional levels were low in all four. One patient had AAE induced by oral contraceptives. The C1Inh plasma level was normal but the functional level was very low; there were no autoantibodies. Symptoms resolved when oral contraceptives were withdrawn and the C1Inh level returned to normal. DISCUSSION: Treatment of AAE is a difficult matter. For type I AAE, it consists in treating the associated disease. For type II AAE, the treatment goal is to lower the autoantibody level. Management of these diseases requires close collaboration between clinicians and biologists.
Adult↗
Tetanus toxin L chain is processed by major histocompatibility complex class I and class II pathways and recognized by CD8+ or CD4+ T lymphocytes.
Tetanus toxin (TeNT) is a heterodimeric protein antigen, whose light chain (L) is translocated in the cytosol of neuronal target cells specifically to cleave its substrates, vesicle-associated membrane protein-2 (VAMP-2, or synaptobrevin) or cellubrevin. We report that the L chain behaves as a nominal antigen recognized by specific T-cell clones upon either class I- or II-restricted presentation. Three types of responses are observed: (i) a TeNT- and L-specific CD8+ T-cell response, that can be inhibited in a dose-dependent manner by the proteasome inhibitor clasto-Lactacystin beta-lactone; (ii) a CD4+ T-cell response specific for L but not TeNT, with recognition of a determinant processed in a chloroquine-sensitive and brefeldin A-resistant compartment; (iii) a CD4+ T-cell response against both L and TeNT, with processing in a brefeldin A-sensitive compartment. The L chain processing was investigated in U937 cells by internalization and localization of L chain by separation of the cell content by differential centrifugation experiments. After incubation with TeNT or L chain in the presence of H chain, the L chain was predominantly distributed in the cytosolic fraction, whereas incubation with L alone led to localization in a lysosome/membrane fraction. The distribution of the TeNT L chain in both cytosolic and endocytic compartments of the antigen-presenting cell accounted for its processing by both class I and class II pathways. Furthermore, an epitope overlapping with the zinc-binding region was recognized by CD4+ and CD8+ T cells.
Antigen-Presenting Cells↗
Hepatitis C virus NS3 serine protease interacts with the serpin C1 inhibitor.
Both NS3 protein (1007-1657) and its protease moiety (NS3p, 1027-1207) were able to interact in vitro with C1 Inhibitor (C1Inh) to give a 95-kDa Mr C1Inh cleavage product similar to that obtained upon proteolysis by complement protease C1s. High-Mr reaction products were also detected after incubation of C1Inh with NS3 but not with NS3p; they correspond to ester-bonded complexes from their hydroxylamine lability. Similar reactivity of NS3 was observed upon incubation with alpha2-antiplasmin. Serpin cleavage was prevented by treatment of NS3 with synthetic serine protease inhibitors. This interaction between viral NS3 and host serpins suggests that NS3 is likely to be controlled by infected cell protease inhibitors.
Complement C1 Inactivator Proteins↗
Importance of thioredoxin in the proteolysis of an immunoglobulin G as antigen by lysosomal Cys-proteases.
For disulphide-bonded antigens, reduction has been postulated to be a prerequisite for proteolytic antigen processing, with subsequent production of major histocompatibility complex (MHC) class II binding fragments. The murine monoclonal immunoglobulin G (IgG) CE25/B7 was used as a multimeric antigen in a human model. Native IgG is highly resistant to proteolysis and has been previously found to be partially reduced at early steps of cell processing to become a suitable substrate for endopeptidases. The role of the oxidoreductase thioredoxin (Trx) was assessed in the reduction of the IgG by cleavage of H-L and H-H disulphide bonds. Recombinant human Trx (rTrx) has been assayed in a proteolytic in vitro system on IgG using endosomal and lysosomal subcellular fractions from B lymphoblastoid cells. rTrx is required in a dose-dependent manner for development of efficient proteolysis, catalysed by thiol-dependent Cys-proteases, such as cathepsin B. We demonstrated that cathepsin B activity was stimulated by the addition of rTrx. Thus, we propose that Trx-dependent IgG proteolysis occurred, on the one hand by means of the unfolding of the IgG after disulphide reduction, becoming a substrate of lysosomal proteases, and on the other hand by Cys-proteases such as cathepsin B that are fully active upon the regeneration of their activity by hydrogen donors.
Cathepsin B↗
Co-operation between human CR1 (CD35) and CR2 (CD21) in internalization of their C3b and iC3b ligands by murine-transfected fibroblasts.
CR1 and CR2 are expressed as associated proteins on the B-lymphocyte surface. To investigate their respective contributions to the internalization of C3 fragments, transfected murine fibroblasts expressing human CR1, CR2, or both CR1 and CR2 were produced. CR1- and CR1-CR2-expressing cells bound C3b and C3b-dimer whereas CR2- and CR1-CR2-expressing cells bound iC3b and C3de. In all cases, maximum binding was achieved at low ionic strength. CR1-CR2-positive cells internalized two- to threefold more C3b and 1.5-fold more iC3b than CR1- and CR2-single-positive cells, respectively. Internalization of the anti-CR1 antibody J3D3, or C3de was at the same level, in both double-transfected and single-transfected cells. Furthermore, the internalization of C3b dimer by CR1-CR2 cells was impaired in the presence of OKB7, an anti-CR2-blocking antibody, but it was not altered in CR1 cells. Taken together, these findings suggest that CR1 and CR2 collaborate to internalize C3b and iC3b proteins. We suggest that the induction of conformational changes of the ligands enhances their binding to both receptors.
Animals↗
EBV-B cells as antigen presenting cells in characterization of the self/donor context of allorecognition by T lymphocytes.
Alloreactivity is caused by T cell recognition of foreign histocompatibility antigens according to two models: (i) indirect recognition, in which processed allogeneic antigens are presented by self-major histocompatibility complexes like any other foreign antigen, and (ii) direct recognition, where the foreign MHC itself is recognized breaking the T cell recognition rule of self-restriction. This paper uses these two cases of alloantigen presentation as illustrative examples to investigate (i) the capacity of Epstein-Barr virus-transformed B cells (EBV-B cells) to process alloantigens, and (ii) in vitro assays with EBV-B cell lysate as a source of alloantigen, in order to characterize alloreactive T cell populations. A microculture system was established using donor EBV-B cell lysate as a source of the allogeneic antigen and donor or recipient EBV-B cells as antigen presenting cells to investigate whether alloantigen is recognized by effector T cells from the recipient. T lymphocytes produced after expansion in the presence of interleukin-2 from four samples of liver biopsies (three patients) and four samples of bronchoalveolar lavages (four patients) were used as effector cells. Upon human leucocyte antigen class II typing, these expressed the patient phenotype. When the T lymphocytes were from liver grafts, the recognition involved donor antigens presented by donor EBV-B cells (direct recognition). On the other hand, when the T lymphocytes were cultured from lung grafts, they mainly recognized antigens of donor EBV-B cell lysates in a self-restricted context (indirect recognition). These data suggest that EBV-B cells can provide allogeneic determinants recognized by T cells in donor or self-contexts, i.e. through either direct or indirect recognition.
Adult↗
Treatment of severe Crohn's disease with anti-CD4 monoclonal antibody.
BACKGROUND: Monoclonal CD4 antibodies have been proposed as a new immunosuppressant drug in the treatment of inflammatory bowel disease. We report our experience of treatment with a monoclonal anti-CD4 (B-F5) antibody in severe refractory Crohn's disease. METHODS: Twelve patients with severe refractory Crohn's disease were treated in an open clinical trial. B-F5 was given intravenously at a dose of 0.5 mg. day/kg for 7 consecutive days (patients 1-8). For patients 9-12, B-F5 was given at a dose of 0.5 mg. day/kg on the first day (day 0) and of 1 mg.day/kg on days 1-6. Follow-up examinations were carried out at days 8, 15, 22 and 30. Endoscopic evaluation was performed on days 0 and 30 in eight of 12 patients. RESULTS: Immediately after the first infusion, one patient had dyspnoea and tachycardia requiring cessation of the treatment. Among the 11 patients who received the complete course of treatment, two had prolonged clinical improvement and two had partial clinical improvement. Significant endoscopic improvement was observed in only one patient. No sustained depletion of CD4+ cells could be observed. CONCLUSION: In this uncontrolled open trial, monoclonal anti-CD4 B-F5 antibody was not successful in severe Crohn's disease.
Adolescent↗
Monoclonal IgG as antigens: reduction is an early intracellular event of their processing by antigen-presenting cells.
Murine mAb injected into patients behave as exogenous antigens and trigger a specific immune response characterized mainly by CD4+ T lymphocytes. They are recognized by T cells under a processed form and in a MHC class II-restricted fashion. IgG degradation which occurs in antigen-presenting cells (APC) has been studied in vitro. We have shown that partial reduction of this antigen is an early event which is significant for the generation of class II-restricted fragments presentable to antigen-specific T cells. Two different murine mAb were used as antigens and human monocytic U937 or antigen non-specific Epstein-Barr virus-transformed B cells as APC. Upon cellular internalization IgG are rapidly cleaved leading to 24-25 kDa fragments. One of the major and early events corresponds to partial reduction of IgG--the light chain is released from the intact molecule, heavy chains remaining bound together. Partial in vitro reduction of IgG followed by presentation by fixed B cells to specific T cells showed that only kappa light chain-specific T cell clones are stimulated, in contrast to heavy chain-specific T cell clones. The response to the kappa chains of specific T cells points to a significant role played by the early IgG partial reduction in the generation of kappa light chain class II binding fragments.
Antibodies, Monoclonal↗