A 1-Year Prospective French Nationwide Study of Emergency Hospital Admissions in Children and Adults with Primary Immunodeficiency.

Purpose: Patients with primary immunodeficiency (PID) are at risk of serious complications. However, data on the incidence and causes of emergency hospital admissions are scarce. The primary objective of the present study was to describe emergency hospital admissions among patients with PID, with a view to identifying "at-risk" patient profiles.

[Autoantibodies as biomarkers].

Activation and differentiation of autoreactive B-lymphocytes lead to the production of autoantibodies, which are thus the direct consequence of the autoimmune process. They often constitute biomarkers of autoimmune diseases and are measured by tests displaying various diagnosis sensitivity and specificity. Autoantibody titers can be correlated to the disease activity and certain autoantibody populations associated with particular clinical manifestations or tissue lesions.

Autosomal dominant STAT3 deficiency and hyper-IgE syndrome: molecular, cellular, and clinical features from a French national survey.

Autosomal dominant deficiency of signal transducer and activator of transcription 3 (STAT3) is the main genetic etiology of hyper-immunoglobulin (Ig) E syndrome. We documented the molecular, cellular, and clinical features of 60 patients with heterozygous STAT3 mutations from 47 kindreds followed in France. We identified 11 known and 13 new mutations of STAT3.

Evidence for a protective role of the STAT5 transcription factor against oxidative stress in human leukemic pre-B cells.

STAT5 transcription factors are involved in normal B lymphocyte development and in leukemogenesis. We show that the inhibition of STAT5A expression or activity in the NALM6, 697 and Reh leukemic pre-B cell lines, results in a higher spontaneous apoptosis and an increased FAS-induced cell death. However, the molecular mechanisms underlying the altered pre-B cell survival are unclear.

Synovium CD20 expression is a potential new predictor of bone erosion progression in very-early arthritis treated by sequential DMARDs monotherapy -- a pilot study from the VErA cohort.

Objective: Because available biomarkers (rheumatoid factors [RF], anti-cyclic citrullinated autoantibodies [anti-CCP2], erythrocyte sedimentation rate at 1st hour [ESR]/C-reactive peptide [CRP] and bone erosions) are insufficient to predict rheumatoid arthritis (RA) structural damage, to determine whether synovium expression of greater or equal to 1 markers could constitute new prognostic factor(s).

Method: The study was conducted on 18 prospectively enrolled disease-modifying anti-rheumatic drug (DMARD)- and glucocorticoid-naïve, VErA cohort patients with very-early arthritis (median duration: 4months). Recorded at baseline were: clinical and biological (serum ESR, CRP, RF-isotypes, anti-CCP2, osteoprotegerin, receptor activator of nuclear κB-ligand [RANK-L] and cartilage oligomeric matrix protein [COMP] levels) data; synovium expression (HLA-DR, CD163, CD3, CD20, VEGF, osteoprotegerin, RANK-L, Bcl2 and global inflammation index) for a metacarpophalangeal joint-synovium biopsy.

Frequent and widespread vascular abnormalities in human signal transducer and activator of transcription 3 deficiency.

Background: Signal transducer and activator of transcription 3 (STAT3) deficiency is responsible for autosomal dominant hyperimmunoglobulin E syndrome, characterized by recurrent bacterial and fungal infections, connective tissue abnormalities, hyperimmunoglobulin E, and Th17 lymphopenia. Although vascular abnormalities have been reported in some patients, the prevalence, characteristics, and etiology of these features have yet to be described.

Methods And Results: We prospectively screened 21 adult STAT3-deficient patients [corrected] (median age, 26 years; range, 17-44 years) [corrected] for vascular abnormalities.

Parental consanguinity is associated with a severe phenotype in common variable immunodeficiency.

The DEFI study has collected clinical data and biological specimens from kindreds with CVID. Patients with demonstrated parental consanguinity (cCVID group) were compared to patients without parental consanguinity (ncCVID). A total of 24 of the 436 patients with CVID had consanguineous parents.

A 5-year prospective follow-up study in essential cryofibrinogenemia patients.

Introduction: Cryofibrinogenemia may be essential, or secondary to diseases such as neoplasia, infection, thrombosis, and collagen vascular diseases. In a previous study, we reported the occurrence of neoplasia in some essential cryofibrinogenemia patients after a short period of follow-up.

Purpose: We performed a prospective multi-center 5-year follow-up study in essential cryofibrinogenemia patients (2005-2009).

Enzyme-linked immunosorbent assay for the combination of bullous pemphigoid antigens 1 and 2 in the diagnosis of bullous pemphigoid.

Objective: To assess the usefulness of enzyme-linked immunosorbent assay (ELISA) assessment of the combination of bullous pemphigoid antigen 1 (BPAG1) and BPAG2 in the diagnosis of bullous pemphigoid (BP).

Design: Retrospective study of serum samples from patients with BP.

Setting: Tertiary care center.

Correlation of anti-signal recognition particle autoantibody levels with creatine kinase activity in patients with necrotizing myopathy.

Objective: Anti-signal recognition particle (anti-SRP) autoantibodies are associated with severe acquired necrotizing myopathies. The role of these autoantibodies remains elusive, and the evolution of anti-SRP levels over time is unknown. In this study, we developed an addressable laser bead immunoassay (ALBIA) technique to investigate a correlation between anti-SRP levels, serum creatine kinase (CK) levels, and muscle strength in patients with necrotizing myopathy.

Role of toll-like receptor 4 in the inflammation reaction surrounding silicone prosthesis.

The inflammation which occurs around the silicone prosthesis is a complex process that can provoke the failure of the device and compromise the health of the implanted patient. Toll-like receptors (TLRs), which are transmembrane proteins, are now known to act in the innate immune response and in endogenous inflammation. The aim of our study was to assess the role of TLR4 in the foreign body reaction to a silicone shell prosthesis.

Human duodenal proteome modulations by glutamine and antioxidants.

Purpose: Glutamine (Gln) has protective, anti-inflammatory effects in animal models and humans. Antioxidant nutrients may exert synergistic effects on intestinal functions. Therefore, these combined nutrients may have a therapeutic potential during intestinal inflammation.

Gene profiling predicts rheumatoid arthritis responsiveness to IL-1Ra (anakinra).

Objectives: The overall non-response rate to biologics remains 30-40% for patients with RA resistant to MTX. The objective of this study was to predict responsiveness to the anakinra-MTX combination by peripheral blood mononuclear cell gene profiling in order to optimize treatment choice.

Methods: Thirty-two patients treated with anakinra (100 mg/day s.

Spectrum of autoantibodies other than anti-desmoglein in pemphigus patients.

Background: Pemphigus is a life-threatening autoimmune blistering disease mediated by autoantibodies against adhesion molecule of the skin. Its concurrence with systemic and organ-specific autoimmune disease was described in case reports.

Objectives: To evaluate the presence of a broad spectrum of organ-specific and non-organ-specific autoantibodies other than anti-desmoglein antibodies in pemphigus patients.

Serum IgA rheumatoid factor and pyridinoline in very early arthritis as predictors of erosion(s) at two years: a simple model of prediction from a conservatively treated community-based inception cohort.

Objective: To identify, in conservatively treated, very early arthritis patients, predictors of ≥1 erosion(s) at 2 years, and to construct a prediction model.

Methods: Community-based adults (n=310) who had never taken disease-modifying antirheumatic drugs (DMARDs) or steroids with swelling of ≥2 joints persisting for >4 weeks and lasting <6 months were recruited. Erosion status was assessed at 0, 6, 12, and 24 months; evaluations were comprised of clinical criteria (Disease Activity Score, Health Assessment Questionnaire), C-reactive protein level, erythrocyte sedimentation rate, autoantibodies, bone and cartilage markers, hand densitometry, and HLA class II shared epitopes.

[Acute pseudo-membranous laryngitis in epidermolysis bullosa acquisita].

Epidermolysis bullosa acquisita is a rare entity belonging to the auto-immune cutaneous blistering disorders of the dermo-epidermal junction. Clinical manifestations are generally cutaneous including the development of sub-epidermal blisters. Mucosal manifestations should be systematically looking for, but laryngeal involvement remains uncommon.

Critical role of TLR2 and TLR4 in autoantibody production and glomerulonephritis in lpr mutation-induced mouse lupus.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by pathogenic autoantibodies directed against nuclear Ags and immune complex deposits in damaged organs. Environmental factors have been thought to play a role in the onset of the disease. The recognition of these factors is mediated by TLRs, in particular TLR2 and TLR4 which bind pathogen-associated molecular patterns of Gram(+) and Gram(-) bacteria, respectively.

Early and long-standing rheumatoid arthritis: distinct molecular signatures identified by gene-expression profiling in synovia.

Introduction: Rheumatoid arthritis (RA) is a heterogeneous disease and its underlying molecular mechanisms are still poorly understood. Because previous microarray studies have only focused on long-standing (LS) RA compared to osteoarthritis, we aimed to compare the molecular profiles of early and LS RA versus control synovia.

Methods: Synovial biopsies were obtained by arthroscopy from 15 patients (4 early untreated RA, 4 treated LS RA and 7 controls, who had traumatic or mechanical lesions).

Diagnostic and prognostic usefulness of antibodies to citrullinated peptides.

The diagnosis of rheumatoid arthritis (RA) must be made early, because prompt initiation of treatments tailored to disease activity is crucial to improve structural and functional outcomes. Anti-citrullinated peptide antibodies (ACPAs) are well-established diagnostic markers for RA and should be included in the classification criteria. Here, we describe the main tests for detecting ACPAs and we underline the diagnostic and prognostic usefulness of ACPAs in patients with RA.

Tunisian endemic pemphigus foliaceus is associated with the HLA-DR3 gene: anti-desmoglein 1 antibody-positive healthy subjects bear protective alleles.

Background: Pemphigus foliaceus is an autoimmune blistering skin disease that partly results from genetic factors, especially human leucocyte antigen (HLA) class II genes.

Objectives: The aim of the study was to determine the HLA DR/DQ markers of susceptibility and protection in the Tunisian endemic form.

Methods: Genomic DNA from 90 patients with pemphigus foliaceus recruited from all parts of the country and matched by age, sex and geographical origin with 270 healthy individuals, was genotyped.

Can rheumatoid arthritis responsiveness to methotrexate and biologics be predicted?

This review briefly recapitulates the existing markers predictive of RA responsiveness to treatment, focusing on MTX alone or combined with a biologic. In addition to the demographic and clinical factors, an update is provided of the predictive biomarkers identified by large-scale gene and protein analyses that generated new insights into the ability of high-throughput analysis of biological systems to select new potential indicators. Among the large-scale analysis tools now available, pharmacogenetics and pharmacogenomics (including transcriptomic and proteomic approaches) have been shown to provide such new putative biomarkers of therapeutic responses.

Anti-desmoglein 1 antibodies in healthy related and unrelated subjects and patients with pemphigus foliaceus in endemic and non-endemic areas from Tunisia.

Background: Pemphigus foliaceus is an autoimmune blistering skin disease characterized by the production of pathogenic IgG autoantibodies directed against desmoglein 1.

Aim: To determine the prevalence of anti-desmoglein 1 antibodies in healthy subjects and their distribution in the different regions of Tunisia and to better identify endemic areas of pemphigus foliaceus.

Methods: We tested, by enzyme-linked immunoserbent assay, sera of 270 normal subjects recruited from different Tunisian areas and 203 related healthy relatives to 90 Tunisian pemphigus foliaceus patients.

ELISA testing of anti-desmoglein 1 and 3 antibodies in the management of pemphigus.

Objective: To assess the predictive value of anti-desmoglein (Dsg) 1 and anti-Dsg3 antibody (Ab) enzyme-linked immunosorbent assay (ELISA) values for the occurrence of relapses in pemphigus.

Design: Retrospective study.

Setting: Dermatology departments from 13 university hospitals in France.