Serological proteome analysis reveals new specific biases in the IgM and IgG autoantibody repertoires in autoimmune polyendocrine syndrome type 1.

Objective: Autoimmune polyendocrine syndrome type 1 (APS 1) is caused by mutations in the AIRE gene that induce intrathymic T-cell tolerance breakdown, which results in tissue-specific autoimmune diseases.

Design: To evaluate the effect of a well-defined T-cell repertoire impairment on humoral self-reactive fingerprints, comparative serum self-IgG and self-IgM reactivities were analyzed using both one- and two-dimensional western blotting approaches against a broad spectrum of peripheral tissue antigens.

Methods: Autoantibody patterns of APS 1 patients were compared with those of subjects affected by other autoimmune endocrinopathies (OAE) and healthy controls.

An Optimized Fluorescence-Based Bidimensional Immunoproteomic Approach for Accurate Screening of Autoantibodies.

Serological proteome analysis (SERPA) combines classical proteomic technology with effective separation of cellular protein extracts on two-dimensional gel electrophoresis, western blotting, and identification of the antigenic spot of interest by mass spectrometry. A critical point is related to the antigenic target characterization by mass spectrometry, which depends on the accuracy of the matching of antigenic reactivities on the protein spots during the 2D immunoproteomic procedures. The superimposition, based essentially on visual criteria of antigenic and protein spots, remains the major limitation of SERPA.

Immune profile modulation of blood and mucosal eosinophils in nasal polyposis with concomitant asthma.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently associated with asthma. Mucosal eosinophil (EO) infiltrate has been found to correlate with asthma and disease severity but not necessarily in every patient. Other multifactorial immune processes are required to determine disease endotypes and response to treatment.

CD3-CD4+ lymphoid variant of hypereosinophilic syndrome: nodal and extranodal histopathological and immunophenotypic features of a peripheral indolent clonal T-cell lymphoproliferative disorder.

The CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome is characterized by hypereosinophilia and clonal circulating CD3(-)CD4(+) T cells. Peripheral T-cell lymphoma has been described during this disease course, and we observed in our cohort of 23 patients 2 cases of angio-immunoblastic T-cell lymphoma. We focus here on histopathological (n=12 patients) and immunophenotypic (n=15) characteristics of CD3(-)CD4(+) lymphoid variant of hypereosinophilic syndrome.

The lymphoid variant of hypereosinophilic syndrome: study of 21 patients with CD3-CD4+ aberrant T-cell phenotype.

The CD3-CD4+ aberrant T-cell phenotype is the most described in the lymphoid variant of hypereosinophilic syndrome (L-HES), a rare form of HES. Only a few cases have been reported, and data for these patients are scarce. To describe characteristics and outcome of CD3-CD4+ L-HES patients, we conducted a national multicentric retrospective study in the French Eosinophil Network.

Milder multiple sclerosis course in patients with concomitant inflammatory bowel disease.

An association between multiple sclerosis (MS) and inflammatory bowel disease (IBD) has been suggested. The purpose of this study was to compare the disease course of patients with both MS and IBD with that of patients with isolated MS or isolated IBD. Sixty-six MS-IBD patients were identified and were matched with 251 isolated MS and 257 isolated IBD controls.

The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia: New Insights Based on a Survey of 44 Cases.

Imatinib is the treatment of choice for FIP1L1/PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P CEL), but its optimal dosing, duration, and possibility of discontinuation are still a matter of debate. A retrospective multicenter study was conducted with 44 F/P CEL patients identified in the French Eosinophil Network and treated with imatinib. The most frequently involved systems were skin (57%), spleen (52%), and lung (45%), and eosinophilic heart disease was observed in 15 patients (34%).

Changes Related to Age in Natural and Acquired Systemic Self-IgG Responses in Malaria.

Background. Absence of acquired protective immunity in endemic areas children leads to higher susceptibility to severe malaria. To investigate the involvement of regulatory process related to self-reactivity, we evaluated potent changes in auto-antibody reactivity profiles in children and older subjects living in malaria-endemic zones comparatively to none-exposed healthy controls.

Primed status of transitional B cells associated with their presence in the cerebrospinal fluid in early phases of multiple sclerosis.

In the present study we showed that transitional B cells of patients with clinically isolated syndrome (CIS) and relapsing-remitting multiple sclerosis (RR-MS) are reduced in the peripheral blood (PB) (5.5- and 3.7-fold, respectively).

Comparative proteomic analysis of blood eosinophils reveals redox signaling modifications in patients with FIP1L1-PDGFRA-associated chronic eosinophilic leukemia.

The FIP1L1-PDGFRA (F/P) fusion gene, which was identified as a recurrent molecular finding in hypereosinophilic syndrome (HES), lead to a constitutively increased tyrosine kinase activity of the fusion protein. Despite data obtained in animals or cell lines models, the mechanisms underlying the predominant eosinophil lineage targeting and the cytotoxicity of eosinophils in this leukemia remain unclear. To define more precisely intrinsic molecular events associated with F/P gene, we performed a proteomic analysis comparing F/P+ eosinophils (F/P-Eos) and eosinophils from healthy donors (C-Eos).

B-cell subsets up-regulate α4 integrin and accumulate in the cerebrospinal fluid in clinically isolated syndrome suggestive of multiple sclerosis onset.

During the pathogenesis of multiple sclerosis (MS), activated B-cells cross the inflamed endothelium of the central nervous system (CNS) to exert their effector functions, probably associated with the action of several adhesion molecules. B-cell mobilization towards the CNS already occurs after the first demyelinating events suggestive of MS, known as clinically isolated syndrome (CIS). However, little is known about the role of these adhesion molecules at this early disease stage.

Susceptibility to experimental autoimmune encephalomyelitis is associated with altered B-cell subsets distribution and decreased serum BAFF levels.

B cells possess the ability to regulate either pathogenic or protective events in several autoimmune diseases such as multiple sclerosis (MS) and its experimental model, experimental autoimmune encephalomyelitis (EAE). Given the extensive use of B-cell-targeting treatments, it appears crucial to more precisely define the dual role of B cells in the progression of the disease. In the present study, we explored the impact of EAE induction on the distribution of potential regulatory B-cell subsets (CD5(+) B1a, marginal zone and transitional 2 B cells) over critical time points in the relapsing-remitting EAE model, SJL/J (H2s).

Comparison of the Farr radioimmunoassay, 3 commercial enzyme immunoassays and Crithidia luciliae immunofluorescence test for diagnosis and activity assessment of systemic lupus erythematosus.

Backgrounds: Among anti-double-strand (ds)DNA antibody assays, Farr radioimmunoassay is decreasingly used because it requires radioactive material and is labor intensive. We evaluated the performance of Farr, three commercial enzyme immunoassays (EIAs) and the Crithidia luciliae immunofluorescence test (CLIFT) in systemic lupus erythematosus (SLE).

Methods: Anti-dsDNA antibodies were determined in 99 SLE patients, 101 healthy subjects, and 53 patients with autoimmune rheumatic diseases.

Diluted Russell viper-venom time improves identification of antiphospholipid syndrome in a lupus anticoagulant-positive patient population.

The objective of this retrospective study was to evaluate the potential ability of diluted Russell viper-venom time (dRVVT) to identify antiphospholipid syndrome (APS) in a lupus anticoagulant (LA)-positive patient population, already selected by other LA clotting tests. Our cohort of positive LA patients was first identified in our outpatients population by the following sensitive LA-detecting tests: Rosner index, diluted prothrombin time (dPT) and Rosove index. Then the 227 consecutive LA-positive patients were tested for dRVVT with the same blood sample.

Characterization of discriminant human brain antigenic targets in neuropsychiatric systemic lupus erythematosus using an immunoproteomic approach.

Objective: To characterize discriminant human brain antigenic targets in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), using a standardized immunoproteomic approach.

Methods: Self-IgG reactivity against normal and injured human brain tissues was studied by Western blotting of sera from 169 subjects, 16 patients with NPSLE, 12 patients with SLE without neuropsychiatric manifestations (non-NPSLE), 32 patients with Sjögren's syndrome with or without central nervous involvement, 82 patients with multiple sclerosis, and 27 healthy subjects. A proteomic approach was then applied to characterize discriminant antigens identified after comparisons of all patterns.

Changes in self-reactive IgG antibody repertoire after treatment of experimental autoimmune encephalomyelitis with anti-allergic drugs.

We reduced EAE severity by using two anti-allergic drugs. A control group of mice received i.p.

Diversified serum IgG response involving non-myelin CNS proteins during experimental autoimmune encephalomyelitis.

We sequentially analyzed the serum IgG response against normal mouse brain during experimental autoimmune encephalomyelitis in SJL/J mice injected with CFA, Bordetella pertussis toxin (BPT) and proteolipid protein 139-151 peptide, compared with mice that received CFA and BPT or were uninjected. Dynamic changes were observed from day 0 to day 28 in the 3 groups. Six highly discriminant antigenic bands (kappa=0.

[Treatment of hypereosinophilia].

Therapeutic management of blood hypereosinophilia depends on its underlying cause. The cause may be clearly established (parasitic infestation) or more hypothetical (systemic disease). Blood eosinophils often return to normal levels after treatment of either the cause or the associated eosinophilic disease.

Comparative evaluation of two applications for delivering a multimedia medical course in the French-speaking Virtual Medical University (UMVF).

This paper describes a comparative evaluation of two applications delivering a multimedia course: a conventional web server (WS) and an integrated e-learning platform in the form of a virtual campus (VC). We used a qualitative method for comparing their acceptance of the on-line course provided by the two different interfaces. The two groups were globally satisfied.

Evolution of self-reactive IgG antibody repertoires in patients with relapsing-remitting multiple sclerosis.

We have previously demonstrated a distortion of self-reactive IgG antibody repertoires in patients with multiple sclerosis (MS) compared to controls, by immunoblotting assays, using human brain homogenates. The analysis of the immune profiles against human brain antigens allowed us to distinguish MS patients, and to associate a particular pattern of reactivity for each clinical form of MS. The aim of the present study was to evaluate the evolution of such patterns in patients with relapsing-remitting MS (RRMS).

New insights into cell responses involved in experimental autoimmune encephalomyelitis and multiple sclerosis.

Animal models of autoimmune diseases such as experimental autoimmune encephalomyelitis (EAE) are inflammatory demyelinating diseases which comprise a heterogeneous group of disorders that affect the peripheral and central nervous systems. EAE presents close similarities with multiple sclerosis (MS), a chronic inflammatory disease affecting central nervous system (CNS) white matter. Many studies have shown EAE to be a particularly useful animal model for the understanding of both the mechanisms of immune-mediated CNS pathology and the progressive clinical course of multiple sclerosis.