B-cell epitopes of the intracellular autoantigens Ro/SSA and La/SSB: tools to study the regulation of the autoimmune response.

A common serologic finding in systemic autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Although their pathogenesis is not fully understood, autoantibodies are important tools for establishing diagnosis, classification and prognosis of autoimmune diseases. In Systemic Lupus Erythematosus (SLE) and Sjögren's syndrome (SS) autoantibodies mainly target multicomponent ribonucleoprotein complex Ro/La RNP.

Autoimmune response and target autoantigens in Sjogren's syndrome.

Background: Primary Sjogren's syndrome (pSS) is characterized by the presence of autoantibodies targeting mainly the Ro/La ribonucleoprotein complex. It is now appreciated that the production of autoantibodies is an antigen-driven immune response.

Design: In this review, candidate mechanisms for autoantigen presentation and perpetuation of the autoimmune response within the autoimmune tissue lesion of pSS are discussed.

Idiotype, anti-idiotype network of autoantibodies: pathogenetic considerations and clinical application.

A common serologic finding in autoimmune diseases is the presence of autoantibodies against intracellular autoantigens. Recent data suggest that an anti-idiotypic network exists in these diseases, regulating the production of autoantibodies (idiotypic response). The anti-idiotypic antibodies can be monitored using complementary epitopes, designed according to the “molecular recognition” theory.

Epigenetics in autoimmune disorders: highlights of the 10th Sjögren's syndrome symposium.

During the 10th International Symposium on Sjögren's Syndrome held in Brest, France, from October 1-3, 2009 (http://www.sjogrensymposium-brest2009.org), the creation of an international epigenetic autoimmune group has been proposed to establish gold standards and to launch collaborative studies.

Accurate detection of changes in disease activity in primary Sjögren's syndrome by the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index.

Objective: To assess and compare the sensitivity to change of the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) with that of other primary Sjögren's syndrome (SS) disease activity indexes.

Methods: We abstracted 96 patient profiles, including data on 3 successive visits (visits 1-3), from the medical charts of patients with primary SS. Patient profiles were scored with the ESSDAI, SS Disease Activity Index (SSDAI), and Sjögren's Systemic Clinical Activity Index (SCAI).

Ovarian function is preserved in women with severe systemic lupus erythematosus after a 6-month course of cyclophosphamide followed by mycophenolate mofetil.

Objective: To evaluate whether a short duration treatment with cyclophosphamide (CYC) followed by mycophenolate mofetil (MMF) is associated with preservation of the ovarian function in female patients with systemic lupus erythematosus (SLE).

Methods: We retrospectively evaluated 61 premenopausal women with SLE treated for lupus nephritis (n=58), autoimmune hemolytic anemia (n=1) and central nervous system involvement (n=2). Thirty-nine patients received prolonged treatment with 1 g/m2 intravenous (IV) CYC pulses (group I).

Prevalence and outcome of pulmonary fibrosis in microscopic polyangiitis.

We sought to determine the type of pulmonary involvement in microscopic polyangiitis (MPA), primarily focusing on pulmonary fibrosis (PF), its prevalence, temporal relationship with other disease manifestations and outcome. 33 patients (16 males) with biopsy proven perinuclear anti-neutrophilic cytoplasmic antibody-positive MPA (age 63.5 yrs) participated in the study.

RNA recognition motif (RRM) of La/SSB: the bridge for interparticle spreading of autoimmune response to U1-RNP.

Systemic lupus erythematosus (SLE) is characterized by the production of grouped sets of autoantibodies targeting mainly the U1 ribonucleoprotein (RNP) and/or Ro/La RNP particles. Intraparticle diversification of the autoimmune response is believed to occur via epitope spreading. So far, it is not known how the autoimmune response "jumps" from one particle to another.

Diffuse malignant peritoneal mesothelioma presenting as intestinal obstruction.

Diffuse malignant peritoneal mesothelioma (DMPM) represents 90% of all peritoneal forms of mesothelioma. It affects mainly patients 50-69 years old. In 50% of cases there is a history of asbestos exposure.

Functional expression of the alpha 2-macroglobulin receptor CD91 in salivary gland epithelial cells.

CD91 molecule is a multifunctional receptor of alpha 2-macroglobulin, heat-shock proteins and calreticulin. CD91 has been implicated in cross-presentation of peptides chaperoned by these proteins to MHC molecules, thus eliciting antigen-specific immune responses. Hence, CD91 is considered as a major regulator of innate and acquired immune responses.

EULAR Sjogren's syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren's syndrome.

Objective: To develop a disease activity index for patients with primary Sjögren's syndrome (SS): the European League Against Rheumatism (EULAR) Sjögren's syndrome disease activity index (ESSDAI).

Methods: Thirty-nine SS experts participated in an international collaboration, promoted by EULAR, to develop the ESSDAI. Experts identified 12 organ-specific 'domains' contributing to disease activity.

Prevalence of hepatitis C serum antibody in autoimmune diseases.

Objective: To evaluate the prevalence of serum antibodies against hepatitis C virus and other infectious agents in a large cohort of well-characterized patients with autoimmune diseases (AID).

Methods: We utilized 1322 sera from patients with 18 different AID and 236 sera from healthy controls from the same countries and with similar age and sex distribution. All sera were tested for the presence of serum anti-hepatitis C virus (HCV) antibodies as well as antibodies directed at other infectious agents and autoantibodies.

Mortality in Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune disease that involves primarily the exocrine glands and results in their functional impairment. The disease may occur alone (primary SS, pSS) or in association with other autoimmune diseases, such as rheumatoid arthritis (secondary SS, sSS). Although the clinical manifestations of pSS patients are mainly those of an autoimmune exocrinopathy, 40% to 50% of patients develop extraglandular disease, which may be manifested either by epithelial lymphocytic invasion of lung, liver, or kidney (resulting in interstitial nephritis) or by skin vasculitis, peripheral neuropathy, glomerulonephritis, and low C4 levels, conditions which represent an immune-complex mediated disease.

Neuroendocrine dysfunction in Sjogren's syndrome.

Interactions among the immune, nervous and endocrine systems, which are mediated by hormones, neuropeptides, neurotransmitters, cytokines and their receptors, appear to play an important role in modulating host susceptibility and resistance to inflammatory disease. The neuroendocrine system has two main components: the central and the peripheral. The central compartment is located in the locus ceruleus, the brainstem centers of the autonomic system and the paraventricular nucleus; the peripheral mainly consists of the sympathetic/adrenomedullary system, the hypothalamic-pituitary-adrenal axis (HPA), the hypothalamic-pituitary-gonadal (HPG) axis, and the neuroendocrine tissue located in several organs throughout the body.

Ultrasonography of salivary glands: an evolving approach for the diagnosis of Sjögren's syndrome.

Sjögren's syndrome (SS) is a chronic autoimmune rheumatic disease, which primarily affects the exocrine glands. The diagnosis of SS is based on American-European diagnostic criteria that include, as independent diagnostic items, imaging techniques such as sialography and scintigraphy. In recent years, new imaging techniques--including MRI, magnetic resonance sialography and ultrasonography of the salivary glands--have been used to diagnose SS.

Upregulation of antiphospholipid antibodies following cyclophosphamide therapy in patients with systemic lupus erythematosus.

Objective: We have observed several cases of patients with systemic lupus erythematosus (SLE) who developed antiphospholipid antibodies (aPL) or full blown antiphospholipid syndrome (APS) after being successfully treated with cyclophosphamide (CYC). To further evaluate the significance of this phenomenon we undertook a retrospective study of our patient population with SLE.

Methods: The charts of 320 patients with SLE, either CYC treated (n = 117) or non-treated (n = 203), were reviewed.

Thoracoabdominal motion in ankylosing spondylitis: association with standardised clinical measures and response to therapy.

Objectives: To assess the relationship between thoracoabdominal motion during quiet breathing and standardised indices of disease severity in patients with ankylosing spondylitis (AS); also to evaluate whether thoracoabdominal motion improves after institution of biological agents in these patients.

Methods: Displacement of the rib cage (RC) and abdomen (Abd) during quiet breathing in the sitting, standing and supine position were recorded by impedance plethysmography in 60 patients (mean (SD) age 41 (10) years, 56 men) and 21 healthy men (mean (SD) 36 (7) years). x-y plots of RC versus Abd displacement during quiet breathing were constructed, and the angle of the slope of the RC-Abd loop was calculated and averaged for five consecutive breaths.

Selective screening of secretory vesicle-associated proteins for autoantigens in type 1 diabetes: VAMP2 and NPY are new minor autoantigens.

The four major autoantigens (IA-2, IA-2 beta, GAD65 and insulin) of type 1 diabetes are all associated with dense core or synaptic vesicles. This raised the possibility that other secretory vesicle-associated proteins might be targets of the autoimmune response in type 1 diabetes. To test this hypothesis 56 proteins, two-thirds of which are associated with secretory vesicles, were prepared by in vitro transcription/translation and screened for autoantibodies by liquid phase radioimmunoprecipitation.

Update on Sjögren's syndrome autoimmune epithelitis: from classification to increased neoplasias.

Sjögren's syndrome is a chronic inflammatory process that primarily involves the exocrine glands. Its clinical manifestations range from autoimmune exocrinopathy to extraglandular (systemic) involvement affecting the lungs, kidneys, blood vessels, and muscles; it can occur alone (primary Sjögren's syndrome) or in association with other autoimmune diseases (secondary Sjögren's syndrome). In recent years, clinical and laboratory observations have highlighted the central role of the epithelial cell and it has been suggested that the etiological name of the disease should be 'autoimmune epithelitis'.

Sjögren's syndrome--study of autoantigens and autoantibodies.

The presence of autoantibodies is the hallmark of systemic autoimmune diseases. During the past 30 years, intense clinical and basic research have dissected the clinical value of autoantibodies in many autoimmune diseases and offered new insights into a better understanding of the molecular and functional properties of the targeted autoantigens. Unraveling the immunologic mechanisms underlying the autoimmune tissue injury, provided useful conclusions on the generation of autoantibodies and the perpetuation of the autoimmune response.

Properties and function of polyreactive antibodies and polyreactive antigen-binding B cells.

The advent of hybridoma technology has made it possible to study in-depth individual antibody molecules. These studies have revealed a number of surprises that have and are continuing to change our view of the immune system. None of these was more surprising than the demonstration that many antibody molecules are polyreactive - that is they can bind to a variety of different and structurally unrelated self- and non-self-foreign antigens.

Human chorionic gonadotropin prevents Sjögren's syndrome-like exocrinopathy in mice.

Objective: Results of recent studies suggest that human chorionic gonadotropin (HCG), a placental glycoprotein hormone required for the maintenance of pregnancy, may have immunomodulatory properties. Primary Sjögren's syndrome (SS), a chronic autoimmune disorder of unknown etiology, affects multiple exocrine glands including the salivary and lacrimal glands. The purpose of the present study was to determine whether HCG could prevent the development of salivary gland exocrinopathy in NOD mice, an experimental model of Sjögren's-like syndrome.

Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial.

Objective: To evaluate the safety and effectiveness of adalimumab alone or in combination with standard disease-modifying antirheumatic drugs (DMARDs) for the treatment of rheumatoid arthritis (RA).

Methods: Patients with active RA despite treatment with DMARDs or prior treatment with a tumour necrosis factor antagonist participated in a multicentre, open-label clinical study of adalimumab 40 mg every other week for 12 weeks with an optional extension phase. Patients were allowed to continue with pre-existing traditional DMARDs.

Expression of functional Toll-like receptors by salivary gland epithelial cells: increased mRNA expression in cells derived from patients with primary Sjögren's syndrome.

Toll-like receptors (TLR) play an essential role in the activation of both innate and adaptive immune responses. Salivary gland epithelial cells (SGEC) may participate in the development of glandular inflammatory reactions that characterize primary Sjögren's syndrome (pSS). In this study we sought to assess the expression and function of several TLR molecules in cultured non-neoplastic SGEC obtained from pSS patients and disease controls.