A longitudinal approach for constructing beta-expectation tolerance intervals.

A new method is presented for constructing beta-expectation tolerance limits (TLs) for longitudinal data with error components regression structure. The TLs are mainly intended for small samples where the variation between and within subjects is large. In such cases the new method is superior to existing methods, which are based on a cross-sectional approach and which do not utilize the longitudinal structure of the data.

A prospective study of sicca symptoms in patients with rheumatoid arthritis.

Objective: To investigate sicca symptoms in patients with rheumatoid arthritis (RA) with respect to constancy, temporal changes of prevalence, and possible risk factors.

Methods: A prospective cohort study of 70 patients with RA was conducted over 5 years. The main variables of interest were the 6 questions on sicca symptoms used in the preliminary European criteria for Sjögren's syndrome.

Attenuated apoptosis of B cell activating factor-expressing cells in primary Sjögren's syndrome.

B cell activating factor (BAFF) is known to be a powerful regulator of B-cell differentiation and proliferation. The aim of this study was to assess the incidence of apoptosis among BAFF-expressing cells in Sjögren's syndrome (SS) salivary gland tissue. We performed double stainings of BAFF together with one of the markers, CD21, CD68, CD40, Fas, Bcl-2 or Bax, and monitored apoptosis among BAFF expressing cells by using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-digoxigenin nick-end labeling method.

Increased salivary gland tissue expression of Fas, Fas ligand, cytotoxic T lymphocyte-associated antigen 4, and programmed cell death 1 in primary Sjögren's syndrome.

Objective: To assess salivary gland tissues obtained from patients with primary Sjögren's syndrome (SS) for the gene expression profile of the candidate genes TNFRSF6 (Fas), TNFSF6 (FasL), SSA1 (Ro52 alpha and the splice variant Ro52 beta), SSB (La), CTLA4, PDCD1 (PD-1), and ORM2, which were selected on the basis of their putative participation in salivary gland inflammation.

Methods: Quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine the expression of messenger RNA (mRNA). Tissue localization of the expressed proteins was detected by immunohistochemistry.

A prospective cross-sectional study of speech in patients with the 22q11 deletion syndrome.

Unlabelled: The purpose of this study was to investigate a consecutive series of 65 participants between 3 and 33 years of age (median age of 9 years and 4 months) with a confirmed 22q11.2 deletion, in order to ascertain the frequency and severity of articulation difficulties, velopharyngeal impairment (VPI), and the level of intelligibility. The majority had velopharyngeal impairment; over half of them to such a degree that surgery had been performed or was considered necessary.

Leukocyte protein calprotectin and outcome in rheumatoid arthritis. A longitudinal study.

Objective: To determine if calprotectin is predictive for outcome in patients with rheumatoid arthritis (RA).

Methods: Fifty six RA in-patients with variable disease duration were prospectively followed for five years. Clinical and laboratory data were collected to assess disease activity.

CD40, CD154, Bax and Bcl-2 expression in Sjögren's syndrome salivary glands: a putative anti-apoptotic role during its effector phases.

Sjögren's syndrome (SS) is an autoimmune rheumatic disorder characterized by chronic lymphocytic infiltration and decreased secretion in the salivary glands (SGs). For some time, apoptosis has been suggested to constitute the major mechanism for acinar epithelial destruction during the effector phases; however, this is still controversial. We have recently demonstrated that despite the expression of Fas and FasL, the incidence of apoptosis is not increased in SS patients compared with control individuals.

Genetic aspects of Sjögren's syndrome.

Sjögren's syndrome is a multisystem inflammatory rheumatic disease that is classified into primary and secondary forms, with cardinal features in the eye (keratoconjunctivitis sicca) and mouth (xerostomia). The aetiology behind this autoimmune exocrinopathy is probably multifactorial and influenced by genetic as well as by environmental factors that are as yet unknown. A genetic predisposition to Sjögren's syndrome has been suggested on the basis of familial aggregation, animal models and candidate gene association studies.

Selective down-regulation of aquaporin-1 in salivary glands in primary Sjögren's syndrome.

Salivary and lacrimal gland secretions are reduced in primary Sjögren's syndrome (pSS). Aquaporins (AQPs) are involved in transmembrane water transport, and different isoforms show specific cellular and subcellular distributions in salivary and lacrimal glands. Changes in expression of AQP molecules have therefore been suggested to contribute to the glandular dysfunction in pSS.

Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjögren's syndrome.

The Ro52, Ro60 and La48 autoantigens are associated with Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE). The mechanisms behind tolerance breakdown of these self-peptides remain unclear; however, apoptosis has been proposed to cause their presentation to the immune system. We have examined the localization of transiently expressed enhanced green fluorescent protein (EGFP)-tagged Ro52, Ro60 and La48 autoantigens in a human salivary gland (HSG) cell line by laser confocal microscopy under normal growth conditions and during apoptosis.

A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans.

Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified.

The evolution and breakdown of the immune system: implications for development of autoimmune diseases.

At the most recent meeting of the Scandinavian Society for Immunology in Bergen, one of the major target phenomena was autoimmune diseases. The approach started from the evolutionary origins of immunity, went on to review some of the notable advances in molecular architecture of immune processes and finally focussed the findings on autoimmune disease.

Current issues in Sjögren's syndrome.

Sjögren's syndrome is a chronic autoimmune and rheumatic disorder with prominent sicca complaints from the mucous membranes because of lack of proper exocrine secretions. There is no straightforward and simple diagnostic test for Sjögren's syndrome, although several classification criteria have been designed including several oral diagnostic tests. A new set of classification criteria in a joint effort by research groups in Europe and USA has recently been presented.

Classification criteria for Sjögren's syndrome: a revised version of the European criteria proposed by the American-European Consensus Group.

Classification criteria for Sjögren's syndrome (SS) were developed and validated between 1989 and 1996 by the European Study Group on Classification Criteria for SS, and broadly accepted. These have been re-examined by consensus group members, who have introduced some modifications, more clearly defined the rules for classifying patients with primary or secondary SS, and provided more precise exclusion criteria.

Abnormal B cell differentiation in primary Sjögren's syndrome results in a depressed percentage of circulating memory B cells and elevated levels of soluble CD27 that correlate with Serum IgG concentration.

The percentage of CD27(+) B cells in peripheral blood (PB) of patients with primary Sjögren's syndrome (pSS) is significantly decreased compared to normals. In contrast, serum levels of the soluble form of CD27 (sCD27) are significantly higher in pSS patients, with a strong positive correlation between sCD27 and serum IgG levels. In vitro experiments demonstrate that normal B cells cultured under conditions driving plasma cell differentiation result in the production of substantial amounts of sCD27.

Clinical, immunological, and immunogenetic aspects of autoantibody production against Ro/SSA, La/SSB and their linear epitopes in primary Sjögren's syndrome (pSS): a European multicentre study.

Objectives: To investigate the clinical and immunogenetic aspects of antibody formation against Ro/SSA and La/SSB as well as their linear B cell epitopes in patients with primary Sjögren's syndrome (pSS) from different European countries.

Patients And Methods: Ninety patients with pSS from six European centres were studied. Serum samples from all patients were tested in a control laboratory for anti-Ro/SSA and anti-La/SSB autoantibodies by RNA precipitation assay and autoantibodies to the previously reported B cell linear epitopes of Ro 60 kDa (p169-190aa and p211-232aa) and La/SSB (p147-154aa, p291-302aa, p301-318aa, and p349-364aa).

Parenteral vaccination against influenza does not induce a local antigen-specific immune response in the nasal mucosa.

The immune response in the nasal mucosa to influenza vaccination in 23 patients scheduled for tonsillectomy was studied. A statistically significant increase in influenza virus-specific serum and oral fluid antibodies was observed 7 days after vaccination. The numbers of influenza virus-specific antibody-secreting cells (ASCs) in peripheral blood also increased significantly 1 week after vaccination.

Autoantibodies in primary Sjögren's syndrome: new insights into mechanisms of autoantibody diversification and disease pathogenesis.

Characterisation of autoantibodies and their target autoantigens in primary Sjögren's syndrome (SS) is an important entry point for studying this common systemic autoimmune disease. Diversification of anti-Ro/La responses is believed to occur by a process of determinant spreading following initiation of an autoimmune response to one component, possibly 52-kD Ro (Ro52). Recent evidence supports the ER-resident chaperone Grp78 as a potential candidate in the initiation of an autoimmune response against Ro52, by binding to a Grp78 binding motif in the COOH-terminal region of Ro52.

Increased expression of fas ligand in human tuberculosis and leprosy lesions: a potential novel mechanism of immune evasion in mycobacterial infection.

To study the location and mechanism of apoptosis within the human tuberculosis (TB) and leprosy lesions, parallel sections were analyzed for mycobacterial antigens (M.Ag), Fas ligand (FasL), Fas, CD68 and Mac387 by immunohistochemistry, and apoptotic cells by the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick end labelling method. Cutaneous leishmaniasis and foreign body granulomas were analyzed for comparison.

Up-regulation of M3-muscarinic receptors in labial salivary gland acini in primary Sjögren's syndrome.

M3-muscarinic receptors (M3R) mediate parasympathetic cholinergic neurotransmission to salivary and lacrimal glands, and autoantibodies to these receptors have been implicated in sicca symptoms and autonomic dysfunction in Sjögren's syndrome. We have investigated the expression of M3R in paraffin-embedded labial salivary glands (LSG) from seven patients with primary Sjögren's syndrome (pSS) and five healthy controls using high-resolution confocal microscopy and an affinity-purified goat polyclonal antibody raised against the COOH-terminal sequence of the human M3R. Immunolocalization of M3R was similar in control and pSS glands, with punctate staining of M3R in the basal membrane of acinar cells and in the luminal and abluminal membrane of myoepithelial cells.

The genetic control of sialadenitis versus arthritis in a NOD.QxB10.Q F2 cross.

The non-obese diabetic (NOD) mouse spontaneously develops diabetes and sialadenitis. The sialadenitis is characterized by histopathological changes in salivary glands and functional deficit similar to Sjögren's syndrome. In humans, Sjögren's syndrome could be associated with other connective tissue disorders, such as rheumatoid arthritis.

Subcellular distribution of aquaporin 5 in salivary glands in primary Sjögren's syndrome.

Secretions from salivary and lacrimal glands are reduced in patients with primary Sjögren's syndrome (PSS). Since aquaporin 5 is involved in transport of water and is present in salivary and lacrimal glands, this protein was thought to have a major role in the pathogenesis of PSS. We used indirect immunofluorescence and an immunoperoxidase technique to assess expression and subcellular localisation of aquaporin 5 in patients and controls.

Serum and cerebrospinal fluid pathology in patients with sudden sensorineural hearing loss.

The serum and cerebrospinal fluid (CSF) pathology of patients with sudden sensorineural hearing loss (SHL), both seropositive and seronegative to Borrelia burgdorferi (Bb), was prospectively studied. Nineteen consecutive patients were included and trends between the degree of hearing recovery and serum/CSF pathology and given therapy were examined. The pilot study showed a high prevalence (68%) of pathology in serum and CSF in patients with SHL.