Analysis of low molecular weight intracellular associations of a human mannan binding lectin (MBL).

Human mannan binding lectin (MBL) is a member of the collectins, a group of proteins that contain a dual structure with a lectin and a collagenous moieties. The collectins are considered as major actors of innate immunity. We report the presence of low molecular weight intracellular MBL forms in human hepatocytic cell lysates, with binding capacities associated to its lectin and/or its collagen moiety. Competition with D-mannose and with antibodies directed against the lectin binding site of MBL indicate that the 60 kDa form represents an intracellular association of MBL through its lectin moiety. The effects of collagenase or MBL associated serine proteases (MASPs) from a MBL deficient plasma, gave evidence that the 60 KDa form contains also collagen and suggested the binding of a ligand to this collagen part. These results show that this intracellular form of MBL shares binding properties with circulating MBL. The binding potential of the lectin and the collagenous parts of precursor forms of intracellular MBL may suggest that they behave as molecular chaperone. The complexity of MBL structure and functions deserves further investigation on other intracellular forms of MBL

Efficacy of icatibant treatment in patients with hereditary angio-oedema type I resistant to treatment with C1 inhibitor concentrate.

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Splenic infarction associated with transient anti-prothrombin antibodies is a rare manifestation of acute Mycoplasma pneumoniae infection

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Systematic review: New serological markers (anti-glycan, anti-GP2, anti-GM-CSF Ab) in the prediction of IBD patient outcomes

International audienceTraditionally, IBD diagnosis is based on clinical, radiological, endoscopic, and histological criteria. Biomarkers are needed in cases of uncertain diagnosis, or to predict disease course and therapeutic response. No guideline recommends the detection of antibodies (including ASCA and ANCA) for diagnosis or prognosis of IBD to date. However, many recent data suggest the potential role of new serological markers (anti-glycan (ACCA, ALCA, AMCA, anti-L and anti-C), anti-GP2 and anti-GM-CSF Ab). This review focuses on clinical utility of these new serological markers in diagnosis, prognosis and therapeutic monitoring of IBD. Literature review of anti-glycan, anti-GP2 and anti-GM-CSF Ab and their impact on diagnosis, prognosis and prediction of therapeutic response was performed in PubMed/MEDLINE up to June 2014. Anti-glycan, anti-GP2 and anti-GM-CSF Ab are especially associated with CD and seem to be correlated with complicated disease phenotypes even if results differ between studies. Although anti-glycan Ab and anti-GP2 Ab have low sensitivity in diagnosis of IBD, they could identify a small number of CD patients not detected by other tests such as ASCA. Anti-glycan Abs are associated with a progression to a more severe disease course and a higher risk for IBD-related surgery. Anti-GP2 Ab could particularly contribute to better stratify cases of pouchitis. Anti-GM-CSF Ab seems to be correlated with disease activity and could help predict relapses. These new promising biomarkers could particularly be useful in stratification of patients according to disease phenotype and risk of complications. They could be a valuable aid in prediction of disease course and therapeutic response but more prospective studies are needed

Idiopathic histaminergic angioedema without wheals: a case series of 31 patients

International audienceIdiopathic histaminergic acquired angioedema (IH-AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell-mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH-AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH-AAE). Thirty-one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH-AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti-histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three-fourfold in 16·1% (five patients). IH-AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1-anti-histamines may be necessary to control symptoms

Utilisation de l’hydroxychloroquine et de la prednisone en présence d’une auto-immunité sérique dans l’infertilité féminine

International audiencePresence of non-specific autoimmunity (antinuclear antibodies without antigenic specificities and/or antiphospholipid antibodies without criteria of antiphospholipid syndrome) seems to be associated with unexplained female infertility. The objective is to study the characteristics of patients who undergone treatment for non-specific antibodies in Medically Assisted Procreation (MAP)

Mannan-binding lectin and hepatitis C infection

Japanese patients with chronic hepatitis C infection unresponsive to treatment with interferon possessed genotypes disproportionately conferring low mannan-binding lectin (MBL) concentrations. Our aims were to confirm or refute this finding in European patients at the MBL protein level, and to investigate whether a low circulating concentration of MBL might influence susceptibility to, or disease progression from, hepatitis C viral infection. Serum samples obtained from 180 hepatitis C patients and 566 blood donors were assayed for MBL. MBL concentrations were related to disease characteristics retrieved from patients’ records. MBL concentrations were higher in hepatitis C patients (median 2·5 µg/ml versus 1·3; P < 0·0001) and the proportion of patients with very low (MBL-deficient) concentrations was similar to that of the healthy controls. There were no significant associations between patients with low serum MBL and the disease features studied, including response to antiviral therapy. Therefore, low circulating MBL does not increase susceptibility to hepatitis C infection, and MBL concentration does not have a major influence on the course of the disease or the response to antiviral therapy. MBL replacement therapy would therefore not be indicated for chronic hepatitis C patients who failed to respond fully to treatment with interferon and ribavirin

Auto-antibodies to vascular endothelial cadherin in humans: association with autoimmune diseases.

International audienceTo identify patients with autoimmune diseases who are at high risk of developing vascular cell dysfunction, early biomarkers must be identified. This study was designed to detect and characterize circulating autoantibodies to VE-cadherin (AAVEs) in patients with early-stage autoimmune diseases. An enzyme-linked immunosorbent assay (ELISA) was developed to capture autoantibodies, using a recombinant human VE-cadherin fragment covering the extracellular domains as a target antigen. AAVEs specificity for the target antigen was confirmed by western blotting. Basal AAVEs levels were determined for healthy donors (n=75). Sera from patients (n=100) with various autoimmune diseases, including rheumatoid arthritis (n=23), systemic lupus erythematosus (SLE, n=31), systemic sclerosis (n=30), and Behçet's disease (BD, n=16) were also tested. Levels of AAVEs were significantly higher in rheumatoid arthritis (P<0.0001), SLE (P<0.05), and BD (P<0.05) populations than in healthy subjects. Purified immunoglobulin G (IgG) from a BD patient with exceptionally high AAVEs levels recognized the EC1-4 fragment in western blots. Further characterization of the epitopes recognized by AAVEs showed that BD patients had antibodies specific for the EC3 and EC4 domains, whereas SLE patients preferentially recognized the EC1 fragment. This suggests that distinct epitopes of human VE-cadherin might be recognized in different immune diseases. Purified IgG from BD patients was found to induce endothelial cell retraction, redistribution of VE-cadherin, and cause the formation of numerous intercellular gaps. Altogether, these data demonstrate a potential pathogenic effect of AAVEs isolated from patients with dysimmune disease. This is the first description of AAVEs in humans. Because regions EC1 and EC3-4 have been shown to be involved in homophilic VE-cadherin interactions, AAVEs produced in the course of dysimmune diseases might be specific biomarkers for endothelial injury, which is part of the early pathogenicity of these diseases

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