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ID PMID Title PublicationDate abstract
20497955 Decreased human paraoxonase-1 activity in patients with Sjögren's syndrome. 2010 Jul OBJECTIVES: The aim of the study was to examine human serum paraoxonase 1 (PON1) activity, phenotype distribution and lipid parameters in patients with Sjögren's syndrome. The prevalence of cardio- and cerebrovascular diseases in SS patients was also evaluated after a 5-year follow-up. METHODS: Fifty-seven SS patients and 17 age-matched healthy controls were enrolled into the study. PON1 and arylesterase activities were measured spectrophotometrically. The phenotype distribution of PON1 was determined by the dual-substrate method. RESULTS: Significantly lower PON1 activity was found in patients with SS compared with the control group (98.00 +/- 69.21 versus 203.3 +/- 92.78 U ml(-1); P < 0.001). There were significant differences in PON1 phenotype distribution of SS patients and controls (AA/AB/BB: 91.2/8.8/0 versus 58.8/29.4/11.8%; P < 0.01). No significant correlations were found between PON activity and disease-characteristic autoantibodies, including anti-Ro/SS-A and anti-La/SS-B concentrations. PON activity did not predict the cerebro/cardiovascular risk in SS patients during the 5-year follow-up. CONCLUSIONS: Despite the relatively small sample size that reduces the power of the study, decreased PON activity may be a possible cardiovascular risk factor in SS. Disadvantageous PON1 phenotype distribution may contribute to the decreased PON activity in these patients.
20038904 Assessing the determination of salivary electrolytes and anti-Ro and anti-La antibodies fo 2010 May 1 The aim of this study was to assess changes in salivary electrolyte flow and composition and the presence of anti-Ro/SSA and anti-La/SSB serum and saliva antibodies and their implications for the non-invasive diagnosis of SS. STUDY DESIGN: 73 patients were studied, divided into the following experimental groups: primary Sjögren syndrome (SSp) (n=15), secondary SS (SSs) (n=17), dry mouth, dry eye without Sjögren's syndrome (BO) (n=20) and healthy controls (C) (n=21). We conducted a baseline assessment of salivary flow and saliva sampling for the measurement of sodium, chlorine, potassium, calcium and phosphate electrolytes, and the determination of anti-Ro/SSA and La/SSB antibodies; a serum sampling was made to assess antibody positivity. RESULTS: Salivary flow in SSp, SSs and BO was significantly lower (p<0.001) relative to C. The salivary composition of SS showed an increase of inorganic components. Anti-Ro/SSA and anti-La/SSB antibodies occurred more frequently in serum and saliva in SS patients compared with BO and C, with higher frequency of positivity in serum compared with saliva. CONCLUSION: Our results suggest new tools that could aid the non-traumatic diagnosis of the origin of hyposalivation.
19811798 [Neurosjögren: an unusual presentation with central nervous system involvement]. 2010 Apr INTRODUCTION: Neurological manifestations in Sjögren's syndrome are variable. The peripheral nervous system is generally involved. We report a rare case of an unusual central neurological manifestation. CASE REPORT: A 54-year-old woman was admitted with headache and tetraparesia. The physical examination revealed a tetrapyramidal syndrome and a bilateral parotidomegaly. The patient's general condition was nevertheless quite good. Brain MRI showed an heterogeneous pontine lesion with multiple nodular formations in the periventricular white matter. Blood tests revealed anti-SSA and anti-SSB antibodies. A labial salivary gland biopsy was grade IV in Chisholm scoring system and Schirmer's test was positive. CONCLUSION: A latent Sjögren's syndrome can lead to a wide variety of focal brain MRI abnormalities and should be evoked when the etiology is not clear.
19778440 Rapid serological detection of autoantibodies associated with Sjögren's syndrome. 2009 Sep 24 BACKGROUND: Sjögren's syndrome (SjS) is a relatively common autoimmune disease characterized by oral and ocular dryness. There is an increasing need for simple, sensitive and rapid technologies for the diagnosis of SjS and other autoimmune diseases. Here we investigated whether a quick version of luciferase immunoprecipitation systems (QLIPS) could be used to produce a rapid, specific and quantitative test to detect autoantibodies associated with SjS. METHODS: Using QLIPS, which requires only ten minutes of incubation, a cohort of control and SjS sera were tested for antibodies to three SjS autoantigens (La, Ro60 and Ro52). Sensitivity and specificity of the QLIPS tests were compared with LIPS and existing ELISA data. The QLIPS test for Ro52 was then evaluated with a new validation cohort and its diagnostic performance determined. RESULTS: Using QLIPS, autoantibodies to three SjS antigens, La, Ro60, and Ro52 were detected in 49%, 56% and 70%, respectively, of the SjS patients and none of the controls (100% specificity). With antibody titers in the Ro52-seropositive SjS samples approximately 1,000 times higher than the healthy controls, not only was Ro52 the most informative, but detection of anti-Ro52 antibodies under these non-equilibrium conditions was improved compared to the standard 2 hour LIPS format. Validation of the anti-Ro52 QLIPS test in a new, independent cohort of SjS and control serum samples showed 66% sensitivity and 100% specificity. CONCLUSION: Together these results suggest that the QLIPS format for Ro52 yields both a more rapid and more discriminating test for detecting Ro52 autoantibodies than existing immunoassays and has the potential to be adapted for point-of-care evaluation of patients with SjS and other rheumatologic diseases.
20480165 Polyarteritis nodosa and Sjögren's syndrome: overlap syndrome. 2012 Dec Polyarteritis nodosa (PAN) belongs to a group of necrotic angiitis. During the illness, necrotic changes are found in small and middle dimensions arteries. Primary Sjögren's syndrome is a chronic, autoimmunological systematic illness of connective tissue with characteristic infiltration of lymphocytes and plasmatic cells in endocrine glands. Despite the fact that both disease entities are well known and primary Sjögren's syndrome is the second most commonly appearing autoimmunological sickness, the coexistence of both simultaneously is described very rarely. So far only three such cases have been presented. The case of 53-year-old woman is presented, who since 2003 has been hospitalized due to her ailments several times, at surgery, internal medicine, and rheumatology wards. In 2006, she was admitted to rheumatology clinic of Pomeranian Medical University (PAM) to be diagnosed both subjectively and objectively. Additional examinations proved that she had been suffering from overlapping PAN and primary Sjögren's syndrome (PSS). She fulfilled 5 out of 10 criteria for PAN and all criteria for PSS. For treatment the boluses of methyloprednisolon and cyclophosphamid every 4 weeks were used what resulted in curing the patient.
20080906 Clinical and prognostic significance of parotid scintigraphy in 405 patients with primary 2010 Mar OBJECTIVE: To evaluate the association between the degree of involvement shown by parotid scintigraphy at diagnosis and the disease expression, outcomes, and prognosis of primary Sjögren's syndrome (SS). METHODS: All patients consecutively diagnosed with primary SS in our department between 1984 and 2008 were evaluated. The scintigraphic stages were classified into class 4 (severe involvement), class 2-3 (mild to moderate involvement), and class 1 (normal results). RESULTS: A total of 405 patients with primary SS underwent parotid scintigraphy at diagnosis (47 had class 1 involvement, 314 had class 2-3, and 44 had class 4). Patients with class 4 had a higher frequency of parotid enlargement (p < 0.001), systemic involvement (p = 0.007), high titers of antinuclear antibody (p = 0.016), positive rheumatoid factor (p = 0.002), anti-Ro/SSA (p = 0.001), anti-La/SSB (p = 0.001), low C4 levels (p = 0.001), and low CH50 (p = 0.001) in comparison with the other 2 groups. A higher rate of lymphoma development was observed in patients with class 4 involvement. Adjusted multivariate Cox regression analysis showed a hazard ratio (HR) of 10.51 (p = 0.002) and Kaplan-Meier analysis a log-rank of 0.0005. Mortality was 5-fold higher in patients with class 4 involvement. Adjusted multivariate Cox regression analysis showed an HR of 5.33 (p = 0.001) and Kaplan-Meier analysis a log-rank of 0.033. CONCLUSION: Patients with SS presenting with severe scintigraphic involvement at diagnosis had a more pronounced autoimmune expression, a higher risk of developing systemic features and lymphoma, and a lower survival rate. Study of the degree of salivary gland dysfunction at diagnosis by parotid scintigraphy offers valuable clinical information on the prognosis and outcome of primary SS.
20035924 A simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögre 2010 Mar PURPOSE: To describe, apply, and test a new ocular grading system for assessing keratoconjunctivitis sicca (KCS) using lissamine green and fluorescein. DESIGN: Prospective, observational, multicenter cohort study. METHODS: The National Institutes of Health-funded Sjögren's Syndrome International Registry (called Sjögren's International Collaborative Clinical Alliance [SICCA]) is developing standardized classification criteria for Sjögren syndrome (SS) and is creating a biospecimen bank for future research. Eight SICCA ophthalmologists developed a new quantitative ocular grading system (SICCA ocular staining score [OSS]), and we analyzed OSS distribution among the SICCA cohort and its association with other phenotypic characteristics of SS. The SICCA cohort includes participants ranging from possibly early SS to advanced disease. Procedures include sequenced unanesthetized Schirmer test, tear break-up time, ocular surface staining, and external eye examination at the slit lamp. Using statistical analyses and proportional Venn diagrams, we examined interrelationships between abnormal OSS (>or=3) and other characteristics of SS (labial salivary gland [LSG] biopsy with focal lymphocytic sialadenitis and focus score >1 positive anti-SS A antibodies, anti-SS B antibodies, or both). RESULTS: Among 1208 participants, we found strong associations between abnormal OSS, positive serologic results, and positive LSG focus scores (P < .0001). Analysis of the overlapping relationships of these 3 measures defined a large group of participants who had KCS without other components of SS, representing a clinical entity distinct from the KCS associated with SS. CONCLUSIONS: This new method for assessing KCS will become the means for diagnosing the ocular component of SS in future classification criteria. We find 2 forms of KCS whose causes may differ.
20601836 [An asymptomatic mother of cutaneous neonatal lupus child was diagnosed with Sjögren's sy 2010 We report an asymptomatic mother of a cutaneous neonatal lupus child was diagnosed with Sjögren's syndrome suspected after parturition. A 30-year old woman was visited our hospital to evaluated autoimmune disease because her baby was diagnosed as cutaneous neonatal lupus. Both gum test and Schirmer's test were positive. Antinuclear antibody, anti-SS-A and anti-SS-B antibody were positive. Serum IgG was elevated (2918 mg/dl). Finally, this case was suspected as Sjögren's syndrome. Continuoues follow-up of asymptomatic mothers of a neonatal lupus child is warranted.
20450655 [The clinical characters of 30 patients with enteropathic arthritis and literature review] 2010 Mar OBJECTIVE: To better understand the clinical characters of enteropathic arthritis patients. METHODS: The clinical, laboratory and X-rays data of 30 enteropathic arthritis in-patients were analyzed. RESULTS: Among the 30 patients, 14 were male, 16 were female. Average age at onset of gastroenteric manifestations was 16 - 48 (32.2 +/- 11.0) years old. The course of disease was 1 month - 20 (5.9 +/- 3.4) years. Average age at onset of arthritis was 15 - 52 (43.4 +/- 6.8) years old. The average interval between onset of diarrhea and arthritis was 0 - 13 (4.2 +/- 4.0) years. Peripheral arthritis was founded in 26 (87%) patients, and only 4 felt low back pain at onset. During the disease course, peripheral arthritis in 14 (54%) patients was similar to rheumatoid arthritis. The history of low back pain or buttock pain was recorded in 22 (73%) patients. Extra-articular features including fever occurred in 24 patients, enthesitis in 6, iritis or conjunctivitis in 4, dactylitis in 1 were observed. HLA-B(27) was positive in 36% (9/25) patients. Sacroiliitis in X-ray or CT was observed in 59% patients. CONCLUSION: The clinical manifestations of enteropathic arthritis are characterized by pauciarticular arthritis or symmetric polyarthritis or(and) sacroiliitis, a wide spectrum of extra-articular features, presence of HLA-B(27) and familial history of spondyloarthropathies. As other spondyloarthropathies, the sacroiliitis in enteropathic arthritis was also associated with HLA-B(27).
20403669 B cell lymphoproliferation and organ-directed self-recognition to explain autoimmunity: ba 2010 Sep Autoimmune diseases are characterised by lymphoproliferation in target tissues with B and T lymphocytes often arranged in pseudofollicles, mimicking the structure of peripheral lymph nodes. Target organ tissue damage produces the clinical phenotype which may be diverse ranging from autoimmune endocrinopathies to malabsorption (coeliac disease) to structural damage within bones and joints (rheumatoid arthritis). Recently, B cell depletion has been shown to be effective in many autoimmune conditions suggesting a common pathological origin for these conditions which might be triggered by an autoimmune B cell that has escaped deletion. We postulate that a mutation in a transcription factor early in B cell development might allow persistence and foster proliferation of a clone of autoimmune B cells, capable of producing autoantibodies. A similar common mutation within the JAK2 tyrosine kinase gene has recently been described associated with the myeloproliferative disorders which are also characterised by diverse clinical disease phenotypes. There is considerable evidence that autoimmune diseases could be indolent lymphoproliferative disorders of B-cell origin, extending the forbidden clone hypothesis first proposed in the 1950s.
18926560 The potential of liposomal drug delivery for the treatment of inflammatory arthritis. 2009 Dec OBJECTIVE: To review the use of liposomes as a delivery agent in inflammatory arthritis. METHODS: The literature on liposomes and liposomal drug delivery for the treatment of inflammatory arthritis was reviewed. A PubMed search of articles in the English-language journals from 1965 to 2007 was performed. The index words used were as follows: "rheumatoid arthritis," "liposomes," and "targeted delivery." Papers identified were reviewed, abstracted, and summarized. RESULTS: Liposomes have the capacity to be used as delivery and targeting agents for the administration of antirheumatic drugs at lower doses with reduced toxicity. In other areas of medicine, the pace of progress has been rapid. In the case of infectious diseases and cancer, liposomal drug delivery has progressed and developed into commercially viable therapeutic options for the treatment of fungal infections (amphotericin B), or metastatic breast cancer and Kaposi sarcoma (doxorubicin, daunorubicin), respectively. In arthritis, the efficacy of prednisolone-loaded long-circulating liposomes is currently being evaluated in a phase II clinical trial. Liposome's application to arthritis is still in its infancy but appears promising as new patents are filed. With improvements in liposomal formulation and targeted synovial delivery, liposomes offer increased therapeutic activity and improvement in the risk-benefit ratio. CONCLUSION: Recent research into synovial targets and improved liposomal formulations continues to improve our capacity to use liposomes for targeted delivery. With time, this approach has the potential to improve drug delivery and reduce systemic complications.
21089249 2009 Nov Targeted immune modulators, commonly referred to as biological response modifiers or simply biologics, are a relatively new category of medications used in the treatment of certain types of immunologic and inflammatory diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn’s disease, and ulcerative colitis. The US Food and Drug Administration approved the first of the biologics (infliximab) in 1998 and approved 9 additional agents since that time for treating various rheumatic conditions and plaque psoriasis: etanercept (1998), anakinra (2001), adalimumab (2002), alefacept (2003), efalizumab (2003), abatacept (2005), rituximab (2006), natalizumab (2008), and certolizumab pegol (2008). In this report, we review the comparative effectiveness, safety, and tolerability of targeted immune modulators.
19232069 Osteoimmunology in rheumatic diseases. 2009 This review summarizes the recent advances of osteoimmunology, a new research field that investigates the interaction of the immune system with the skeleton. Osteoimmunology has contributed significantly to the understanding of joint destruction in rheumatoid arthritis and other forms of arthropathies. In particular, the molecular regulation of osteoclast formation and its control by proinflammatory cytokines have helped investigators to understand the mechanisms of bone erosion in rheumatic diseases. Osteoimmunology has also allowed an improvement in our knowledge of the structure-sparing effects of antirheumatic drug therapy. Moreover, recent advances in the understanding of the molecular regulation of osteophyte formation are based on the characterization of the regulation of bone formation by inflammation. This review highlights the key insights into the regulation of bone destruction and formation in arthritis. Moreover, concepts of how bone influences the immune system are discussed.
20411055 Radiation Synovectomy: an effective alternative treatment for inflamed small joints. 2010 Jan An inflamed painful joint is one of the most common indications for the patient to be referred to a rheumatologist or an orthopedician. In relation to the aetiology, the therapeutic approach might be systemic, local or a combination of them in some cases, always with the thought of balancing risk with benefit for the patient. In all cases, independently of the cause, the goal of therapy is to improve the quality of life through the reduction of pain, improvement of mobility and preservation of function. Nuclear Medicine has to offer Radiosynoviorthesis, an effective alternative procedure for treating inflamed small joints. Various radionuclides are available for radiosynoviorthesis. Their selection depends on the size of the joint to be treated. Small joints are mainly treated with [169Er] erbium under a fluoroscopic or sonographic guidance, usually with a simultaneous instillation of a corticoid. Candidates for radiosynoviorthesis should have been under a six-month systemic treatment without encouraging results or should have undergone at least one unsuccessful intra-articular injection of a long acting glucocorticoid. Since 1973, when [169Er] erbium was firstly suggested as a therapeutic agent for radiosynoviorthesis of the finger joints, there has been quite enough experience in its' application. It has been found to be cost effective in providing long term relief of pain and deformity of the inflamed joints in comparison to other therapeutic approaches. Additionally, there is no radiation risk and can be performed on an out patient basis. Therefore it can stand as an effective alternative procedure for treating early stages of chronic synovitis in RA (rheumatoid arthritis) patients, with minor damage of the cartilage and the adjacent bones, and for synovitis secondary to inflammatory arthropathies.
20371884 Alterations in adipocyte glucose transporter GLUT4 and circulating adiponectin and visfati 2010 Mar Rheumatoid arthritis in humans brings about impaired insulin sensitivity and glucose tolerance. Since adipose tissue plays a role in glucose homeostasis, we evaluated the size of adipocytes, the amount of glucose transporter type 4 (GLUT4) in adipocyte plasma membranes, and circulating insulin, glucose, and adipokines affecting glucose metabolism, resistin, adiponectin and visfatin during experimental adjuvant arthritis (AA) in male Lewis rats. AA was induced by a single injection of complete Freund's adjuvans. Adipocyte diameter was assessed microscopically, GLUT4 was measured by Western blotting. Plasma insulin, adiponectin, visfatin were quantitated by RIA, and resistin by ELISA. Arthritic rats showed cachexia, reduced adipocyte size, and downregulated membrane GLUT4 (4065 +/- 962 vs. 9911 +/- 680 arb. units of optic density, p < 0.01), reduced plasma adiponectin (1.956 +/- 0.10 vs. 3.16 +/- 0.22 microg/ml, p < 0.001), and enhanced visfatin (1.84 +/- 1.05 vs. 1.24 +/- 0.1 ng/ml, p < 0.01). Plasma glucose and insulin were unaltered, as were the resistin levels. CONCLUSION: AA induced cachexia results in reduction of adipocyte size, and paradoxically also in downregulation of GLUT4 in adipocyte membranes. This is supposed to be functionally related to the reduced adiponectin levels. The upregulated visfatin in rat arthritis is a novel finding, and it confirms its role in autoimmunity across the species.
20716447 Autoimmunity in 2009. 2010 Oct The number of 2009 publications in indexed journals dealing with 'autoimmunity' has maintained its increasing trend compared to the previous five years. Numerous developments have been proposed in our understanding of systemic and organ-specific autoimmune diseases (particularly multiple sclerosis, systemic lupus erythematosus, and rheumatoid arthritis) and of basic autoimmunity mechanisms (particularly Th17, T regulatory cells, and autoantibodies). Both these lines of evidence share a significant potential to be translated into new therapeutic options to impact clinical practice. This article will discuss selected publications from prominent scientific journals dedicated to immunology and autoimmunity and ultimately include some expectations in branches of autoimmunity that appear promising for future developments.
19863777 Why are women predisposed to autoimmune rheumatic diseases? 2009 The majority of autoimmune diseases predominate in females. In searching for an explanation for this female excess, most attention has focused on hormonal changes--both exogenous changes (for example, oral contraceptive pill) and fluctuations in endogenous hormone levels particularly related to menstruation and pregnancy history. Other reasons include genetic differences, both direct (influence of genes on sex chromosomes) and indirect (such as microchimerism), as well as gender differences in lifestyle factors. These will all be reviewed, focusing on the major autoimmune connective tissue disorders: rheumatoid arthritis, systemic lupus erythematosus and scleroderma.
19480843 Tumor necrosis factor-alpha is a common genetic risk factor for asthma, juvenile rheumatoi 2009 Apr There is a great deal of evidence that points to the association of the tumor necrosis factor-alpha (TNF-alpha) gene as a common genetic factor in the pathogenesis of diseases that are caused by inflammatory and/or autoimmune etiologies. Two single nucleotide polymorphisms (SNPs) identified in the TNF-alpha promoter region have been associated with disease susceptibility and severity. We investigated whether -308G/A and -238G/A TNF-alpha polymorphisms were associated with asthma, systemic lupus erythematosus (SLE), and juvenile rheumatoid arthritis (JRA) in a pediatric Mexican population. In a case-control study of 725 patients (asthma: 226, JRA: 171, and SLE: 328) and 400 control subjects, the participants were analyzed using the allelic discrimination technique. The genotype distribution of both TNF-alpha polymorphisms was in Hardy-Weinberg equilibrium in each group. However, there were significant differences in the allele frequency of TNF-alpha-308A between the patients and the healthy controls. This allele was detected in 2.9% of the controls, 6.0% of asthmatic and JRA patients (p = 0.002 and p = 0.0086), and 6.7% of SLE patients (p = 0.00049); statistical significance was maintained after ancestry stratification (asthma: p = 0.0143, JRA: p = 0.0083, and SLE: p = 0.0026). Stratification by gender showed that the risk for the -308A allele in asthma and JRA was greater in females (OR = 4.16, p = 0.0008 and OR = 4.4, p = 0.0002, respectively). The TNF-alpha -238A allele showed an association only with JRA in males (OR = 2.89, p = 0.004). These results support the concept that the TNF-alpha gene is a genetic risk factor for asthma, SLE, and JRA in the pediatric Mexican population.
18946481 A coding polymorphism in NALP1 confers risk for autoimmune Addison's disease and type 1 di 2009 Mar Variants in the gene encoding NACHT leucine-rich-repeat protein 1 (NALP1), an important molecule in innate immunity, have recently been shown to confer risk for vitiligo and associated autoimmunity. We hypothesized that sequence variants in this gene may be involved in susceptibility to a wider spectrum of autoimmune diseases. Investigating large patient cohorts from six different autoimmune diseases, that is autoimmune Addison's disease (n=333), type 1 diabetes (n=1086), multiple sclerosis (n=502), rheumatoid arthritis (n=945), systemic lupus erythematosus (n=156) and juvenile idiopathic arthritis (n=505), against 3273 healthy controls, we analyzed four single nucleotide polymorphisms (SNPs) in NALP1. The major allele of the coding SNP rs12150220 revealed significant association with autoimmune Addison's disease compared with controls (OR=1.25, 95% CI: 1.06-1.49, P=0.007), and with type 1 diabetes (OR=1.15, 95% CI: 1.04-1.27, P=0.005). Trends toward the same associations were seen in rheumatoid arthritis, systemic lupus erythematosus and, although less obvious, multiple sclerosis. Patients with juvenile idiopathic arthritis did not show association with NALP1 gene variants. The results indicate that NALP1 and the innate immune system may be implicated in the pathogenesis of many autoimmune disorders, particularly organ-specific autoimmune diseases.
19664177 Genome-wide association studies in systemic lupus erythematosus: a perspective. 2009 Genome-wide association studies (GWAS) have been shown to be a powerful way of identifying novel susceptibility genes in systemic lupus erythematosus (SLE), as demonstrated by a series of publications in the past year. Lupus has been a late-comer to the GWAS community, being preceded by success stories for the GWAS approach in other autoimmune diseases, including type I diabetes, ankylosing spondylitis, rheumatoid arthritis, Crohn's disease and ulcerative colitis. The paper by Suarez-Gestal and colleagues seeks to exploit the wealth of data available from a total of four GWAS in SLE, three in European-American populations and one in a Swedish population. The authors describe replication of ten lupus susceptibility alleles in a Spanish SLE case-control study.