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ID PMID Title PublicationDate abstract
18495733 B cell epitopes of the heterogeneous nuclear ribonucleoprotein A2: identification of a new 2009 May OBJECTIVES: Autoantibody formation and T cell reactivity against the heterogeneous nuclear ribonucleoprotein A2 (hnRNP-A2) has been observed in patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Since no differences in epitope recognition were reported and the usefulness of anti-hnRNP-A2 antibodies as diagnostic markers of SLE is unknown, it was our objective to characterise linear B cell epitopes of hnRNP-A2 and to relate the anti-hnRNP-A2 antibody responses to disease activity and clinical features of SLE. METHODS: Sequential serum samples from 15 patients with SLE and sera from patients with other rheumatic diseases and healthy subjects were investigated by ELISA for autoantibody reactivities against a set of 13 overlapping peptides spanning the RNA-binding region of hnRNP-A2. Antibody reactivity against the complete protein was determined by western immunoblotting and ELISA. SLE disease activity was assessed by European Consensus Lupus Activity Measure scores, by SLE Index scores and the British Isles Lupus Assessment index. RESULTS: Anti-peptide antibody reactivities were found in 60% of SLE sera but in only 5% of control samples, and were mainly directed to four peptides, one of which (p155-175) appeared to be immunodominant. Antibodies to p155-175 were exclusively seen in patients with SLE and correlated with clinical disease activity as well as kidney and skin involvement. No correlations were found for the other anti-peptide antibody responses. CONCLUSION: Peptide p155-175 encompasses a disease-specific immunodominant epitope of hnRNP-A2. Since antibodies to p155-175 correlate with disease activity and nephritis, they may be useful as markers for active SLE.
21220083 Tai chi and rheumatic diseases. 2011 Feb Tai chi is a complex multicomponent mind-body exercise. Many studies have provided evidence that tai chi benefits patients with a variety of chronic disorders. This form of mind-body exercise enhances cardiovascular fitness, muscular strength, balance, and physical function and seems to be associated with reduced stress, anxiety, and depression and improved quality of life. Thus, despite certain limitations in the evidence, tai chi can be recommended to patients with osteoarthritis, rheumatoid arthritis, and fibromyalgia as a complementary and alternative medical approach. This article overviews the current knowledge about tai chi to better inform clinical decision making for rheumatic patients.
21189112 Health-related quality of life (EQ-5D) before and after orthopedic surgery. 2011 Feb BACKGROUND AND PURPOSE: Population data on mortality and life expectancy are generally available for most countries. However, no longitudinal data based on the health-related quality of life outcome from the EQ-5D instrument have been reported for orthopedic patients. We assessed the effect of orthopedic surgery as measured by EQ-5D. METHODS: We analyzed EQ-5D data from 2,444 patients who were operated at the Department of Orthopedic Surgery at Karolinska University Hospital, 2001-2005. We also made a comparison between results from this cohort and those from a Swedish EQ-5D population survey. RESULTS: The mean EQ-5D (index) score improved from 0.54 to 0.72. Hip and knee arthroplasty, operations related to previous surgery, trauma-related procedures, and rheumatoid arthritis surgeries had preoperative EQ-5D (index) scores of 0.48 to 0.52. All of these groups showed substantial improvement in scores (0.63 to 0.80). Patients with tumors or diseases of the elbow/hand showed higher preoperative scores (0.66 to 0.77), which were similar postoperatively. In most patients, the EQ-5D (index) score improved but did not reach the level reported for an age- and sex-matched population sample (mean difference = 0.11). INTERPRETATION: Our results can be used as part of the preoperative patient information to increase the level of patient awareness and cooperation, and to facilitate rehabilitation. In future it will be possible-but not easy-to use the EQ-5D instrument as a complementary consideration in clinical priority assessment.
20868565 Imbalance of Th17 to Th1 cells in Behçet's disease. 2010 Jul OBJECTIVES: Behçet's disease (BD) is a helper T cell-mediated autoimmune disease characterised by recurrent orogenital ulcers, uveitis and skin lesions. The helper T cells are divided into Th1, Th2 and Th17 cells according to the pattern of cytokine secretion. Th1 and Th17 cells can contribute to the development of the disease with their respective proinflammatory cytokines, IFN-γ and IL-17. In this study, we investigated the relative role of Th17, Th1 and Th2 cells in BD. METHODS: Peripheral blood mononuclear cells were isolated from 30 patients with BD, for whom the detailed clinical manifestations and medication history were investigated and recorded. Surface markers and intracellular levels of IL-17, IFN-γ and IL-4 in isolated CD4+ T cells were measured using flow-cytometry from these patients and from two control groups, 34 rheumatoid arthritis patients and 24 healthy blood donors to analyse the relationship of Th1, Th17 and Th2 cells in BD. RESULTS: The ratio of Th17/Th1 cells was significantly increased in BD compared to healthy controls (0.16±0.09 vs. 0.10±0.04, p=0.012), while there was no difference in the ratios of Th1/Th2 or Th17/Th2 cells. Th17/Th1 ratio was elevated in BD patients with uveitis or folliculitis compared to those without it (0.21±0.10 vs. 0.13±0.06, p=0.045 for uveitis; 0.18±0.10 vs. 0.12±0.05, p=0.036 for folliculitis). CONCLUSIONS: Our results confirm that TH17 cells are instrumental in Behçet's uveitis and folliculitis. Furthermore, our findings suggest that the role of Th17 cells should be interpreted in the context of their ratio to Th1 cells.
21119343 Receptor activator of nuclear factor kappa B ligand/osteoprotegerin pathway is a promising 2010 Dec Atherosclerotic plaque calcification represents a common pathophysiologic process in the advanced phases of the disease. Both inflammatory and vascular cells (such as osteoblast-like cells, osteoclast-like cells, dendritic cells, macrophages, smooth muscle cells, and endothelial cells) are active players in the balance between intraplaque bone deposition and resorption. Inflammatory processes underlying plaque calcification are regulated by soluble mediators that also contribute to plaque destabilization and increased vulnerability. Among different mediators, the receptor activator of nuclear factor-kappa B (NF-kappa B) ligand (RANKL)/osteoprogerin (OPG) system is a major determinant in inflammatory cell differentiation toward osteoclast-like cells. Thus, this system might be a promising parameter to be investigated as a marker of calcification-related cardiovascular risk and a therapeutic target. Despite some promising results, several limitations have been shown in the potential clinical use of serum RANKL/OPG to better assess the cardiovascular risk. At present, the potential relationship between RANKL/OPG and the content of calcium within the intima of the coronary arteries (CAC score, assessed by computed tomography) needs to be explored in large clinical studies. On the other hand, the antiatherosclerotic relevance of treatments antagonizing RANKL is still under investigation. Despite that clinical evidence is needed, this therapeutic approach might be of particular benefit in selective populations (such as rheumatoid arthritis patients) with an increased cardiovascular risk.
20863729 Acetylenic inhibitors of ADAM10 and ADAM17: in silico analysis of potency and selectivity. 2010 Nov The matrix metalloproteinase family has been a pharmaceutical target for most of the last three decades, but success has been hampered by unwanted side effects caused by lack of selectivity, poor oral bioavailability and decreased potency in vivo. The surface-expressed metalloproteinases ADAM10 and ADAM17, the latter also referred to as TACE, play important roles in various physiological processes, especially involving tissue repair and development. Because of its role in the release of the cytokine TNF-α TACE has been a key target for pharmaceutical intervention in the treatment of rheumatoid arthritis. An extensive body of structural activity data has been developed for a series of small molecule inhibitors of TACE based on a sulfonamide scaffold containing key acetylenic substituents. We have undertaken an extensive molecular modeling study of select members of this ligand group to better understand the structural nuances involved in the development of ever more potent TACE inhibitors, and identify those elements of structure-based design that would enhance the selectivity of such inhibitors for TACE over ADAM10. Results include the identification of a flexible loop, comparable to that found in other MMPs that plays a subtle, yet significant, role in determining inhibitor potency.
20862701 Risk factors for foot and ankle disorders among assembly plant workers. 2010 Dec BACKGROUND: Jobs that necessitate prolonged standing and walking activities are commonly associated with worker's complaints of foot and ankle pain. The objective of this study was to determine the relative contributions of work activity (time spent standing, walking, or sitting), floor surface characteristics, weight, BMI, age, foot biomechanics, and other demographic and medical history factors to the prevalence of foot and ankle disorders. METHODS: A cross-sectional observational study design was used to evaluate employees of an engine manufacturing plant. The main outcome variable was foot or ankle disorders defined by pain and a positive physical examination. The independent variables included baseline demographics, medical history, ergonomic exposures, psychosocial factors, shoe characteristics and foot biomechanics. RESULTS: Twenty-four percent of the cohort met the case definition of foot/ankle disorder with 10% defined as new cases. Fifty-two percent had symptoms of foot/ankle. An increased risk of presenting with foot/ankle disorders was associated with high metatarsal pressure on gait assessment, increased time spent walking, female gender, reported high job dissatisfaction, a history of rheumatoid arthritis, osteoporosis or vascular disorder. For the truck/forklift drivers, an increased number of times getting in and out of the vehicle was associated with a higher prevalence of ankle/foot problems. CONCLUSIONS: An increased risk is associated with higher metatarsal pressure and increased time spent walking. These findings suggest several options for primary and secondary prevention strategies. The use of shoe orthoses with a medial longitudinal arch and metatarsal pad as well as including optional sit/stand workstations may be helpful.
20854813 Mast cell death induced by 24(S),25-epoxycholesterol. 2010 Nov 15 Mast cell is one of the central effectors in inflammatory responses. Recent studies suggest that a promising therapeutic approach for various inflammatory immune diseases, including rheumatoid arthritis, multiple sclerosis, and type I allergies, is to inhibit mast cell growth and/or survival. Studies also indicate that a balanced lipid metabolism is crucial for regulating the life span of cells. Oxysterol is a well-known regulator of lipid metabolism and has diverse functions, such as inhibition of the mevalonate isoprenoid pathway, efflux of free cholesterols, and synthesis of cholesterol esters. Here, we show that 24(S),25-epoxycholesterol, a representative endogenous oxysterol, induces apoptosis in bone marrow-derived murine mast cells. Furthermore, we have revealed, for the first time, that the accumulation of neutral lipids catalyzed by acyl-CoA:cholesterol acyltransferase in the cells was involved in induction of mast cell apoptosis. Our present findings confer new insights into the roles of lipid metabolism during oxysterol-mediated mast cell apoptosis.
20606504 [Occurrence of diabetic ketoacidosis and autoimmune thyroiditis in a patient treated with 2010 Jun Combined pegylated interferon and ribavirin therapy for chronic hepatitis C infection cause a wide range of side effects, including flu-like syndrome, hematological abnormalities, cardiovascular symptoms, gastrointestinal symptoms, pulmonary dysfunction, depression, and retinopathy. Interferon-alpha has been shown to be related to the development of various autoimmune diseases, including systemic lupus erythematosus, rheumatoid arthritis, autoimmune thyroid disease, and type 1 diabetes mellitus (DM). Type 1 DM and thyroid disease respectively develop in 0.08-2.61% and 10-15% of patients treated with combined interferon-alpha and ribavirin for chronic hepatitis C. The coexistence of type 1 DM and autoimmune thyroiditis was rarely reported. We report a case of a 33-year-old female patient with chronic hepatitis C who simultaneously developed diabetic ketoacidosis and autoimmune thyroiditis after treatment with pegylated interferon-alpha 2b and ribavirin.
20087196 Concurrent autoimmune diseases in patients with autoimmune hepatitis. 2010 Mar BACKGROUND: Although the pathomechanisms of autoimmune diseases in various organs remain unresolved, an accumulation of autoimmune diseases in individual patients has been observed. An overlap of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) or primary sclerosing cirrhosis has been well documented. However, the overlap of autoimmune diseases other than PBC or PSC has not yet been investigated in a large cohort. GOAL: The goal of our analysis was to investigate the incidence of concurrent autoimmune diseases in patients with AIH. STUDY: We analyzed our cohort of 278 patients with AIH for concurrent autoimmune diseases. RESULTS: A total of 111 patients (40%) were diagnosed with additional autoimmune diseases. Besides overlap syndromes for PBC and PSC, autoimmune thyroiditis was the most common concurrent disease (28 patients, 10%). Other concurrent autoimmune diseases comprised vitiligo (5 patients), rheumatoid arthritis (5 patients), Sjogren syndrome (4 patients), ulcerative colitis (4 patients), conjunctivitis (4 patients), celiac disease (3 patients), systemic lupus erythematodes (2 patients), type I diabetes (2 patients), multiple sclerosis (2 patients), polymyalgia rheumatica (2 patients), and urticaria (2 patients). One patient each was diagnosed with Crohn's disease, autoimmune gastritis, collagenous colitis, hypophysitis, and sarcoidosis. Investigating 100 patients with polyglandular syndrome and autoimmune thyroid disease for the occurrence of autoantibodies associated with AIH, we identified AIH-associated antibodies only in 1 patient. CONCLUSIONS: Concurrent autoimmune diseases are common in patients with AIH and mirror the full range of known autoimmune diseases. Therefore, an extended diagnostic screening for accumulating autoimmune diseases, especially autoimmune thyroiditis, seems reasonable in patients with AIH.
21165300 Cardiac resynchronization therapy for left ventricular dysfunction induced by chronic righ 2010 Dec Cardiac resynchronization therapy (CRT) has been proven its value in adult patients with congestive heart failure of low ejection fraction and wide QRS duration. Contrast to adult patients, CRT has been rarely applied for young patients. We report on a 9-yr-old boy with progressive left ventricular (LV) dilatation and dysfunction following chronic VVI pacemaker therapy for congenital complete atrioventricular block associated with maternal anti-SSA/Ro and SSB/La antibody. His LV dysfunction was improved after epicardially established CRT.
20457279 Anti-NuMA1 and anti-NuMA2 (anti-HsEg5) antibodies: Clinical and immunological features: A 2010 Aug OBJECTIVE: Anti-NuMA1 and anti-NuMA2 antibodies are antinuclear antibodies (ANA) targeting the mitotic spindle apparatus. Our objective was to determine their clinical and immunological features and to review the literature available data. PATIENTS AND METHODS: Between 2004 and 2008, 36,498 sera were analyzed for the presence of ANA, which included anti-NuMA1 and anti-NuMA2 antibodies. Clinical and immunological features of patients with positive anti-NuMA1 and anti-NuMA2 antibodies (titer> or =1/320) were retrospectively collected and analyzed. A review of the literature was secondly performed. RESULTS: Out of the 36,498 sera analyzed, 10,585 sera were positive for ANA (29%). Out of ANA positive sera, 40 sera (0.38%) (40 different patients) were positive for anti-NuMA antibodies: 27 anti-NuMA1 (0.26%) and 13 anti-NuMA2 (0.12%). Compared to anti-NuMA2 positive patients, anti-NuMA1 positive patients were more often female (81.5% versus 46%; P=0.03), had more frequently a connective tissue disease (CTD) (40.7% versus 0%; P=0.016) and higher serum titers (877+/-466 versus 443+/-278; P=0.007). The anti-NuMA1 positive CTD were either Sjögren's syndrome (SS) (54.5%) or systemic lupus erythematosus (SLE) (45.5%). In the literature, 164 anti-NuMA positive patients (133 anti-NuMA1 and 31 anti-NuMA2) have been reported. Combining the reported cases to ours, up to 67.5% of anti-NuMA positive patients had an autoimmune disease, mostly pSS in 34% (31/90) and SLE in 31% (28/90). Anti-NuMA1 antibodies were the single positive ANA in 46% of anti-NuMA1 positive SS and 47% of anti-NuMA1 positive SLE, and anti-NuMA2 antibodies in 2/2 and 87.5%, respectively. CONCLUSION: Detection of anti-NuMA1 and anti-NuMA2 antibodies is very uncommon. When present, they are mostly associated with connective tissue disease, mainly Sjögren syndrome and systemic lupus. Clinicians may be aware that in these latter conditions, anti-NuMA antibodies may be the single serological marker.
19549537 Response surface optimization of polysaccharides extraction from Liriope roots and its mod 2009 Oct 1 The response surface methodology (RSM) was employed to study the extraction of liriope polysaccharides. The maximum extraction rate (64.1%) of liriope polysaccharides obtained by using the above optimised concentrations of the variables was extraction time (X(1)) at 185min, ratio of liquid to solid (X(2)) at 11, and extraction temperature (X(3)) at 94 degrees C. Forty male Wistar rats were used in the present experiment. After 2 weeks of acclimatization, animals were divided into 5 equal groups: control, SS model and 3 polysaccharides-treatment groups. Rats were orally administered their respective doses every day for 6 weeks. Liriope polysaccharides significantly increased the amount of salivary secretion, and the relative weight of spleen, thymus and submandibular glands. Therefore, the present results revealed that liriope polysaccharides exert a protective effect against tissue damage in rats with sjogren syndrome (SS).
20976785 Acute motor axonal neuropathy in association with Sjögren syndrome. 2010 Nov Sjögren syndrome (SS) has been known to manifest with neurological complications, most frequently of the peripheral nervous system, and often in advance of xerostomia and xerophthalmia. There has been one case report of a patient with SS presenting with acute motor neuropathy similar to Guillain-Barré syndrome (GBS). We report the case of a patient who developed rapidly fulminant acute motor axonal neuropathy (AMAN) with positive anti-GM1 antibody at high titers in association with serological and pathological evidence of SS without xerostomia or xerophthalmia.
19914903 Levels of plasmacytoid dendritic cells and type-2 myeloid dendritic cells are reduced in p 2010 Jun OBJECTIVE: Sjögren's syndrome (SS) is a lymphoproliferative autoimmune disease, characterised by dryness of the mouth and eyes. Dendritic cells (DC) are potent antigen-presenting cells crucial for initiating and maintaining primary immune responses. This study quantified interferon-producing plasmacytoid DC (pDC) and two myeloid DC subsets (mDC1 and mDC2) in peripheral blood (PB) from primary SS (pSS) patients and healthy controls. METHODS: Blood samples from 31 pSS patients and 28 gender and age-matched healthy controls were analysed by flow cytometry using the Miltenyi Blood DC enumeration kit. The presence of pDC in salivary glands (SG) from pSS patients was analysed by immunohistochemistry. RESULTS: Patients with pSS had significantly less pDC and mDC2 in PB compared with healthy controls. Moreover, pDC are present in SG from patients with pSS. CONCLUSION: Patients with pSS have alterations among DC populations in PB, and pDC are present in the SG, suggesting a potential role of these cells in SS.
19523788 Gene expression and chromosomal location for susceptibility to Sjögren's syndrome. 2009 Sep Primary Sjögren's syndrome (SS) is a chronic inflammatory autoimmune disease affecting mainly the exocrine glands. Its physio-pathology is poorly understood and most of the knowledge has been related to the inflammatory component. The aim of this work was to evaluate gene expression profiling in fractions enriched in epithelial cells from labial salivary glands (LSGs) of patients with primary SS and identify chromosomal regions harboring susceptibility genes expressed in epithelial cells. A combined approach of gene expression and genome-wide association study was used. Enriched epithelial cell fractions were obtained from LSGs of patients and controls. Amplified total RNA was labeled and hybridized to 10K cDNA microarrays. Results were normalized and subjected to statistical and functional analysis. A genome-wide microsatellite screen at 10 cM resolution (393 markers) was performed. In salivary gland-epithelial cells from patients 528 genes were expressed differentially in comparison to controls. Pathways not previously linked to disease were found to be altered. Twenty-eight and 15 genes associated with apoptosis were up-regulated and down regulated, respectively. Interferon-related genes, most of which participated in interferon signaling, were also found to be up-regulated. From the genome-wide screen, 6 markers showed evidence of highly significant association with the disease. Of these, five loci harbor genes differentially expressed in patients LSG-epithelial cells. Our results show that in enriched gland-epithelial cells of pSS, both pro-apoptotic/anti-apoptotic and interferon signaling inhibition/stimulation balances may occur. Genes found over-expressed in epithelial cells are candidates for disease susceptibility.
20224222 Correlation between salivary secretion and salivary AQP5 levels in health and disease. 2009 Saliva samples are useful for noninvasive diagnosis of oral and systemic diseases. The water channel protein aquaporin-5 (AQP5) is released into human saliva. Salivary AQP5 levels show a diurnal variation with the secretion of high levels during the waking hours. An age-related decrease in salivary AQP5 levels parallels a decrease in the volume of saliva. Cevimeline, a muscarinic acetylcholine receptor (mAChR) agonist, induces the release of AQP5. Changes in salivary AQP5 levels after cevimeline administration occur simultaneously with changes in saliva flow rate. AQP5 and lipid rafts are released separately from human salivary glands upon M(3) mAChR stimulation. In patients with diabetes mellitus or Sjögren's syndrome, a decrease in salivary secretion occurs concomitantly with low salivary AQP5 levels. Salivary AQP5 levels correlate with salivary secretion in both healthy and disease states, suggesting that changes in salivary AQP5 levels can be used as an indicator of salivary flow rate and the effect of M(3) mAChR agonists on human salivary glands.
19593143 Genetics of systemic lupus erythematosus and Sjögren's syndrome. 2009 Sep PURPOSE OF REVIEW: To determine the advances made in the genetics of systemic lupus erythematosus (SLE) or Sjögren's syndrome as the era of genome-wide association and high-throughput single nucleotide typing begins. RECENT FINDINGS: Several genome-wide association studies have been performed in SLE but there are no such studies published or in progress for Sjögren's syndrome. Genetics and the functional significance of risk alleles in the interferon pathway are being worked out in detail. This is especially true for STAT4 and IRF5. Gene copy number variation, a major source of genetic variability, is important for several genes that impart risk for SLE. An X chromosome copy number dose effect has recently been identified. Genetic evaluation of Sjögren's syndrome is limited to small studies that have concentrated on genes already shown to be risk factors in SLE. SUMMARY: Knowledge of the genetics of SLE is advancing rapidly, whereas that of Sjögren's syndrome lags behind considerably.
20353560 Expression and regulation of HIF-1alpha in macrophages under inflammatory conditions; sign 2010 Mar 30 BACKGROUND: Macrophages expressing the pro-angiogenic transcription factor hypoxia-inducible factor (HIF)-1alpha have been demonstrated in rheumatoid arthritis (RA) in the synovial tissue. Aim of the present study was to investigate intracellular signal transduction regulation of pro-inflammatory HIF-1 alpha expression in macrophages to identify possible new intervention strategies. We investigated the effects of CaMKII-inhibitors amongst other kinase inhibitors, on HIF-1 alpha expression and downstream production of pro-angiogenic factors in macrophages. METHODS: Differentiated THP-1 cells and synovial fluid (SF) macrophages were stimulated with 1 microg/ml LPS with or without pretreatment with specific inhibitors of the ERK pathway (PD98059), the PI3K pathway (LY294002), and the CaMKII pathway (KN93 and SMP-114). mRNA and protein expression of HIF-1 alpha, VEGF, MMP-9, and IL-8 was measured in cell lysates and cell supernatants. RESULTS: HIF-1 alpha protein expression in LPS-stimulated THP-1 macrophages could be blocked by ERK- and PI3K-inhibitors, but also by the CaMKII inhibitor KN93. THP-1 and SF macrophages produced high levels of VEGF, IL-8, and MMP-9, and VEGF protein production was significantly inhibited by PI3K-inhibitor, and by both CaMKII inhibitors. LPS stimulation in an hypoxic environment did not change VEGF levels, suggesting that LPS induced VEGF production in macrophages is more important than the hypoxic induction. CONCLUSIONS: Expression of HIF-1 alpha and downstream effects in macrophages are regulated by ERK-, PI3K, but also by CaMKII pathways. Inhibition of HIF-1alpha protein expression and significant inhibition of VEGF production in macrophages was found using CaMKII inhibitors. This is an unknown but very interesting effect of the CaMKII inhibitor SMP-114, which has been in clinical trial as DMARD for the treatment of RA. This effect may contribute to the anti-arthritic effects of SMP-114.
19151120 Is the development of drug-related lupus a contraindication for switching from one TNF alp 2009 Feb The use of TNF alpha (TNFalpha) inhibitors has made a strong impact on the management of rheumatoid and psoriatic arthritis, ankylosing spondylitis and Crohn disease. Side effects of these agents include the development of autoantibodies and a lupus-like syndrome (drug-related lupus, DRL). Here, a case of a patient who developed DRL while receiving infliximab therapy which resolved spontaneously upon discontinuation of the agent and did not recur with subsequent institution of adalimumab is described. A discussion on the possible pathogenic mechanisms involved in the development of drug-related autoimmunity and differences between the agents is also included.