Functional study of TNF-α promoter polymorphisms: literature review and meta-analysis.

The functional consequences of TNF-α promoter SNPs are still controversial and, to date, the functional consequences of TNF-α haplotype combinations in healthy subjects have not been assessed. In order to assess functional consequences of each TNF-α polymorphism and of their haplotype combination, TNF-α expression and secretion by LPS-stimulated monocytes from 50 healthy subjects were assessed. Monocytes were isolated and cultured for four hours, after 100  ng/mL LPS stimulation.

Induction of B cell-activating factor by viral infection is a general phenomenon, but the types of viruses and mechanisms depend on cell type.

B cell-activating factor of the TNF family (BAFF) plays a key role in promoting B lymphocyte activation and survival. We previously showed in primary Sjögren's syndrome that salivary gland epithelial cells (SGECs), the resident targeted cells of autoimmunity in this disease, can produce BAFF after infection with a double-stranded RNA (dsRNA) virus by a protein kinase RNA (PKR)-dependent mechanism. This study aimed to assess the effect of different viruses on various cell types - SGECs but also dendritic cells (DCs) and monocytes - in the induction of BAFF.

Increased levels of circulating microparticles in primary Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis and relation with disease activity.

Introduction: Cell stimulation leads to the shedding of phosphatidylserine (PS)-rich microparticles (MPs). Because autoimmune diseases (AIDs) are characterized by cell activation, we investigated level of circulating MPs as a possible biomarker in primary Sjögren's syndrome (pSS), systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA).

Methods: We measured plasma levels of total, platelet and leukocyte MPs by prothrombinase capture assay and flow cytometry in 43 patients with pSS, 20 with SLE and 24 with RA and in 44 healthy controls (HCs).

The CGGGG insertion/deletion polymorphism of the IRF5 promoter is a strong risk factor for primary Sjögren's syndrome.

Objective: Interferon regulatory factor 5 is a transcription factor involved in type I interferon (IFN) secretion. This study was undertaken to investigate whether a 5-bp (CGGGG insertion/deletion) promoter polymorphism is involved in genetic predisposition to primary Sjögren's syndrome (SS) and to assess the functional consequences of this polymorphism.

Methods: The exploratory cohort consisted of 185 patients with primary SS and 157 healthy controls, and the replication cohort consisted of 200 patients with primary SS and 282 healthy controls.

Effect of methotrexate and anti-TNF on Epstein-Barr virus T-cell response and viral load in patients with rheumatoid arthritis or spondylarthropathies.

Introduction: There is a suspicion of increased risk of Epstein-Barr virus (EBV)-associated lymphoproliferations in patients with inflammatory arthritides receiving immunosuppressive drugs. We investigated the EBV load and EBV-specific T-cell response in patients treated with methotrexate (MTX) or anti-TNF therapy.

Methods: Data for patients with rheumatoid arthritis (RA) (n = 58) or spondylarthropathy (SpA) (n = 28) were analyzed at baseline in comparison with controls (n = 22) and after 3 months of MTX or anti-TNF therapy for EBV load and EBV-specific IFNgamma-producing T cells in response to EBV latent-cycle and lytic-cycle peptides.

B-cell-activating factor expressions in salivary epithelial cells after dsRNA virus infection depends on RNA-activated protein kinase activation.

B-cell-activating factor (BAFF) plays a key role in promoting activation of autoimmune B cells. This cytokine may be expressed in and secreted by salivary gland epithelial cells (SGEC) after stimulation with type I IFN or viral or synthetic dsRNA. Because this BAFF expression depends only in part on endosomal TLR and type I IFN, we investigated whether other dsRNA sensors could be implicated in BAFF expression.

Viruses induce high expression of BAFF by salivary gland epithelial cells through TLR- and type-I IFN-dependent and -independent pathways.

B cell activating factor (BAFF) plays a key role in promoting B lymphocyte activation. We investigated whether danger signals induce BAFF secretion by cultured salivary gland epithelial cells (SGEC), which are the target of primary Sjögren's syndrome, a prototypic systemic autoimmune disease. SGEC cultures were established from minor salivary glands obtained from ten patients with pSS or sicca symptoms.

Is Inhibitor of differentiation 3 involved in human primary Sjögren's syndrome?

Objectives: Inhibitor of differentiation 3 (Id3)-deficient mice show sicca symptoms, lymphocyte infiltration of exocrine glands and positive anti-Ro/SSA and anti-La/SSB antibodies, all hallmarks of primary Sjögren's syndrome (pSS). The impairment of Id3 in T cells and, possibly, in salivary glandular epithelial cells (SGECs) seems to be involved. This animal model prompted us to investigate the role of Id3 in human pSS.

B-cell activating factor of the tumour necrosis factor family expression in blood monocytes and T cells from patients with primary Sjögren's syndrome.

We investigated B-cell activating factor of the tumour necrosis factor family (BAFF) level in peripheral blood mononuclear cells (PBMCs), monocytes and T cells from patients with primary Sjögren's syndrome (pSS) and controls both ex vivo and in vitro after cytokine stimulation. PBMCs, monocytes and T cells were isolated from 15 patients with pSS and 17 controls. Cells were cultured alone or with interferon (IFN)alpha, IFNgamma and interleukin 10 (IL-10).

Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery.

Rituximab is used in the treatment of lymphoma and autoimmune diseases, for which late-onset neutropenia (LON) were reported. LON-related mechanisms remain unclear. To obtain insights into the mechanisms, we assessed serum, peripheral blood and bone marrow (BM) samples of a patient with LON.

Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjögren's syndrome and systemic lupus erythematosus.

Objective: To analyse B cell activating factor (BAFF) receptor (BAFF-R) expression on peripheral lymphocytes from patients with primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE).

Patients And Methods: Peripheral blood mononuclear cells from 20 patients with pSS, 19 patients with SLE and 15 controls were examined by flow cytometry to investigate BAFF-R mean fluorescence intensity (MFI) on lymphocytes. BAFF-R mRNA level from isolated blood B cells of nine patients with pSS and eight controls was assessed by real-time quantitative reverse transcription-PCR.

Increase of B cell-activating factor of the TNF family (BAFF) after rituximab treatment: insights into a new regulating system of BAFF production.

Background: The cytokine B cell-activating factor of the TNF family (BAFF) is involved in the pathogenesis of autoimmune diseases.

Objective: To access changes in serum protein and mRNA levels of BAFF after rituximab treatment.

Methods: Serum and peripheral blood mononuclear cells (PBMCs) were isolated from five patients (two with lupus, two with Sjögren's syndrome, one with rheumatoid arthritis) before and 12 weeks (range 7-17) after a first course of rituximab infusion.

Tolerance and efficacy of rituximab and changes in serum B cell biomarkers in patients with systemic complications of primary Sjögren's syndrome.

Objective: To investigate the safety and efficacy of rituximab (RTX) for systemic symptoms in patients with primary Sjögren's syndrome (pSS), and changes in B cell biomarkers.

Patients And Methods: The records of 16 patients with pSS according to the American European consensus group criteria were reviewed retrospectively.

Results: Patients, all women, had a median age of 58.

B cell-activating factor of the tumor necrosis factor family (BAFF) is expressed under stimulation by interferon in salivary gland epithelial cells in primary Sjögren's syndrome.

B cell-activating factor (BAFF) has a key role in promoting B-lymphocyte activation and survival in primary Sjögren's syndrome (pSS). The cellular origin of BAFF overexpression in salivary glands of patients with pSS is not fully known. We investigated whether salivary gland epithelial cells (SGECs), the main targets of autoimmunity in pSS, could produce and express BAFF.

No evidence for an association between the -871 T/C promoter polymorphism in the B-cell-activating factor gene and primary Sjögren's syndrome.

Polyclonal B cell activation might be related to pathogenic over-expression of B-cell-activating factor (BAFF) in primary Sjögren's syndrome (pSS) and other autoimmune diseases. We therefore investigated whether BAFF over-expression in pSS could be a primary, genetically determined event that leads to the disease. The complete BAFF gene was sequenced in Caucasian pSS patients and control individuals.

Activation of IFN pathways and plasmacytoid dendritic cell recruitment in target organs of primary Sjögren's syndrome.

Gene expression analysis of target organs might help provide new insights into the pathogenesis of autoimmune diseases. We used global gene expression profiling of minor salivary glands to identify patterns of gene expression in patients with primary Sjögren's syndrome (pSS), a common and prototypic systemic autoimmune disease. Gene expression analysis allowed for differentiating most patients with pSS from controls.

Animal models of HLA-B27-associated diseases: new outcomes.

The HLA-B27 molecule is strongly associated with the spondyloarthropathies, a group of chronic inflammatory diseases, affecting the skeleton, the bowel and the skin. This association has been largely studied, but mechanisms of pathology remain unclear. The HLA-B27 transgenic rats develop a spontaneous disease that strikingly resembles human spondyloarthropathies, dependent of bacterial flora and implicating the immune system.

No evidence for association between 1858 C/T single-nucleotide polymorphism of PTPN22 gene and primary Sjögren's syndrome.

One-third of first-degree relatives of patients with primary Sjögren's syndrome (pSS) suffer from other autoimmune diseases, including type I diabetes, systemic lupus erythematosus and autoimmune thyroiditis. Recently, 1858 C/T polymorphism of PTPN22 gene was reported to predispose to these autoimmune diseases. We decided to investigate whether PTPN22 gene polymorphism was also involved in the genetic predisposition to pSS in a case-control study, including 183 patients with pSS and 172 healthy controls.

Defective costimulatory function is a striking feature of antigen-presenting cells in an HLA-B27-transgenic rat model of spondylarthropathy.

Objective: A disease resembling the human spondylarthropathies develops in HLA-B27-transgenic rats. This disease in rats is mediated by CD4+ T cells, but antigen-presenting cells (APCs) may also play a role. Dendritic cells (DCs) have been reported to be defective in allogeneic mixed lymphocyte culture in this model.

[Do Lewis and MNSS erythrocyte phenotypes predict response to lithium in manic-depressive psychosis?].

Manic depressive psychosis (P.M.D.