Lack of efficacy of etanercept in Sjögren syndrome correlates with failed suppression of tumour necrosis factor alpha and systemic immune activation.

Objective: To provide insight into the clinical failure of the tumour necrosis factor alpha (TNFalpha) inhibitor, etanercept, in primary Sjögren syndrome (pSS), an extensive analysis of the systemic immune profile of patients with pSS was carried out and the effect of etanercept treatment on these immune parameters monitored.

Methods: Peripheral blood mononuclear cells of patients with pSS and healthy controls were compared by flow cytometry to determine differences in distribution of specific cell populations (T cells, B cells, monocytes), and to determine their expression of activation markers (CD25, HLA-DR), TNF receptors and chemokine receptors (CXCR1, 2) before and after treatment. Systemic cytokine levels were measured by multiplex ELISA assay in plasma and in lipopolysaccharide-stimulated whole blood from healthy controls and from patients with pSS before and after etanercept treatment.

Transfer of the AQP1 cDNA for the correction of radiation-induced salivary hypofunction.

The treatment of most patients with head and neck cancer includes ionizing radiation (IR). Salivary glands in the IR field suffer significant and irreversible damage, leading to considerable morbidity. Previously, we reported that adenoviral (Ad)-mediated transfer of the human aquaporin-1 (hAQP1) cDNA to rat [C.

Immunological consequences of thalidomide treatment in Sjögren's syndrome.

Objective: To study the immunological consequences of systemic thalidomide treatment in patients with Sjögren's syndrome.

Methods: Cytokine (tumour necrosis factor alpha (TNFalpha), interleukin (IL) 6) and soluble receptor (sIL2R) levels were measured in patient and control plasma (n = 7), before and after thalidomide treatment. Peripheral blood mononuclear cells were examined by FACS analysis for potential changes in specific cell populations (T cells, B cells, monocytes), and for the expression of activation markers (CD25, HLA-DR), costimulatory molecules (CD40, CD40L), TNF receptors, chemokine receptors, and adhesion molecules (L-selectin (L-sel)).

Serum lipid levels in Sjögren's syndrome.

Objectives: Altered lipid levels may occur in autoimmune diseases, for example low cholesterol levels have been described in rheumatoid arthritis (RA). Serum lipid profiles in patients with Sjögren's syndrome (SS) have not been investigated. We hypothesized decreased lipid levels in SS patients and an inverse relationship with disease activity.

Layered peptide arrays: high-throughput antibody screening of clinical samples.

High-throughput methods to detect and quantify antibodies in sera and other patient specimens have use for many clinical and laboratory studies, including those associated with cancer detection, microbial exposures, and autoimmune diseases. We developed a new technique, termed layered peptide array (LPA), to serve as a screening tool to detect antibodies in a highly multiplexed format. We demonstrate here that a prototype LPA was capable of producing approximately 5000 measurements per experiment and appeared to be scalable to higher throughput levels.

Adult heart block is associated with disease activity in primary Sjögren's syndrome.

Objectives: Congenital heart block occurring in the foetus and neonate may be associated with maternal anti-SS-A/anti-SS-B autoantibodies (anti-SSA/anti-SSB). The adult atrioventricular node is generally thought to be resistant to the damaging effects of anti-SSA/anti-SSB. However, case reports suggest that heart block developing in adult Sjögren's syndrome (SS) patients may be associated with these autoantibodies.

Pilot clinical trial of dehydroepiandrosterone (DHEA) versus placebo for Sjögren's syndrome.

Objective: To screen for potential efficacy and assess feasibility and safety of dehydroepiandrosterone (DHEA) as a treatment for Sjögren's syndrome (SS).

Methods: A 24-week randomized, double-blinded, pilot trial of oral DHEA (200 mg/day) versus placebo was conducted. The primary comparison was to a hypothesized 20% placebo response rate.

Etanercept in Sjögren's syndrome: a twelve-week randomized, double-blind, placebo-controlled pilot clinical trial.

Objective: To assess the safety and potential efficacy of etanercept in the treatment of Sjögren's syndrome (SS).

Methods: This pilot study was a 12-week randomized, double-blind, placebo-controlled trial of etanercept, with 14 subjects in each group. Patients received 25 mg of etanercept or placebo (vehicle) by twice-weekly subcutaneous injection.

Fungal load and candidiasis in Sjögren's syndrome.

Objective: We sought to investigate the prevalence of Candida carriage and the relationships between salivary flow rates and oral Candida load in patients with Sjögren's syndrome (SS).

Methods: The oral Candida load of patients with SS was evaluated by culturing oral rinse (swish and spit) samples. Culture, Gram stain, and wet-mount test results were reported.

Sex steroid hormones in primary Sjögren's syndrome.

Objective: To investigate the relationships between concentrations of sex hormones and measures of disease activity in patients with primary Sjögren's Syndrome (pSS).

Methods: Fifty-four women were evaluated: 39 patients (age, Q1,Q3: 57.0 yrs; 46, 66) diagnosed with pSS and 15 patients (49.

Differentiation of human bone marrow-derived cells into buccal epithelial cells in vivo: a molecular analytical study.

Background: Adult bone marrow-derived (BMD) cells could be used to repair damaged organs and tissues, but the intrinsic plasticity of these cells has been questioned by results of in-vitro studies suggesting that such cells might fuse with other cells giving the appearance of differentiation. We aimed to determine whether fusion events are important in vivo.

Methods: To test whether BMD cells can colonise an epithelial tissue and differentiate there without fusion, we did in-situ hybridisation with Y and X chromosome probes labelled with 35-sulphur or digoxigenin, or labelled fluorescently.

Elevated blood pressure is not related to saliva flow in patients with Sjögren's syndrome.

Objective: The purpose of this study was to determine whether systolic and diastolic blood pressures are associated with salivary flow, dry mouth, or dry eye symptoms in patients with primary Sjögren's syndrome as compared with xerostomic control subjects.

Study Design: One hundred forty consecutive patients seen at the Sjögren's Syndrome Clinic were categorized retrospectively with various classification schemes: (1) subjective dry mouth; (2) subjective dry eye; (3) European criteria; and (4) international criteria. Data collection included age, gender, systolic blood pressure, diastolic blood pressure, salivary flow rate, focus score, Schirmer's test, and laboratory findings, including antinuclear antibodies, anti-SSA, anti-SSB, IgG, IgA, IgM, erythrocyte sedimentation rate, and rheumatoid factor.

Risk factors for positive minor salivary gland biopsy findings in Sjögren's syndrome and dry mouth patients.

Objective: To investigate risk factors for positive minor salivary gland biopsy results in Sjögren's syndrome (SS) and dry mouth patients.

Methods: A total of 289 patients with dry mouth symptoms were evaluated. Potential risk factors for positive minor salivary gland biopsy results (>1 focus of lymphocytes) were studied in 2 phases.