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ID PMID Title PublicationDate abstract
25003427 Impact of Connective Tissue Disease on Oncologic Breast Surgery and Reconstruction. 2016 Jun BACKGROUND: The impact of connective tissue disease (CTD) on outcomes following breast surgery and reconstruction is unknown. The purpose of this study was to evaluate the effect of both CTDs and systemic immunomodulatory therapy on outcomes following breast surgery and reconstruction. METHODS: A retrospective review was performed of all patients from 2005 to 2010 with an active CTD who underwent breast surgery with or without reconstruction. Surgical events were assigned to 1 of 4 groups: ablative surgery alone, autologous reconstruction, implant reconstruction, and revision surgery. Logistic regression was utilized to examine the relationship between complications and type of surgery, CTD diagnosis, and immunomodulatory therapy. Four non-CTD control groups were then compiled for outcome comparison. The a priori P-value was set at P < 0.05, and all tests were 2 sided. RESULTS: Thirty-three patients with CTD underwent112 procedures. Diagnoses included psoriasis/psoriatic arthritis (n = 12), rheumatoid arthritis (n = 10), lupus (n = 4), scleroderma (n = 3), Sjogren syndrome (n = 2), mixed CTD (n = 1), and seronegative polyarthritis (n = 1). Nineteen of 33 (58%) patients who received systemic treatment for CTD in the perioperative period were less likely to experience a minor complication compared with those without treatment (odds ratio= 0.69; P = 0.019). There were no differences in postoperative complications in patients with CTD compared with control groups. CONCLUSIONS: Ablative breast surgery and reconstruction among patients with CTDs can be performed safely with low perioperative complication rates. Patients receiving systemic therapy, and continuing their regimens perioperatively, experience complication rates similar to those not requiring therapy.
26608264 [Biomarkers for chronic inflammatory diseases]. 2015 Dec Inflammatory disorders of childhood, such as juvenile idiopathic arthritis (JIA) and inflammatory bowel disease (IBD) are a challenge for laboratory diagnostics. Firstly, the classical inflammatory markers, such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) often inadequately reflect disease activity but on the other hand there are few specific biomarkers that can be helpful in managing these diseases. Acute phase proteins reflect the systemic inflammatory response insufficiently as their increase is only the indirect result of local inflammatory processes. Modern inflammation diagnostics aim to reflect these local processes and to allow precise monitoring of disease activity. Experimental biomarkers, such as S100 proteins can detect subclinical inflammatory activity. In addition, established laboratory parameters exist for JIA [antinuclear antibodies (ANA), rheumatoid factor (RF), antibodies against cyclic citrullinated peptide (anti-CCP)] and for chronic IBD (fecal calprotectin) that are useful in the treatment of these diseases.
26373564 Inflammatory Bowel Disease in Juvenile Idiopathic Arthritis Patients Treated with Biologic 2015 Nov OBJECTIVE: Evolving inflammatory bowel disease (IBD) is a matter of interest in patients with juvenile idiopathic arthritis (JIA) and might be associated with JIA therapy. METHODS: Data from the German biologics registry (Biologika in der Kinderrheumatologie; BiKeR) from 2001 to 2013 were analyzed. RESULTS: There were 3071 patients with 8389 patient-years (PY) of observation followed. IBD was diagnosed in 11 patients, 8 with Crohn disease and 3 with ulcerative colitis. IBD incidence in patients with JIA was 1.31/1000 PY and higher than published IBD incidences in pediatric populations. Compared with the total BiKeR cohort, patients with IBD more commonly had enthesitis-related arthritis, extended oligoarthritis, psoriatic arthritis, and also rheumatoid factor (RF)-negative polyarthritis. No IBD occurred in patients with systemic JIA or RF-positive polyarthritis. In patients treated with methotrexate (MTX), the IBD incidence was significantly lower compared with patients not treated with MTX. Etanercept (ETN) monotherapy, but not the combination of ETN and MTX, was associated with an increased incidence of IBD. CONCLUSION: Incidence of IBD in patients with JIA is higher than in the population. MTX turned out to be protective, even in combination with ETN.
26510114 Influence of Matrix metalloproteinase 1 and 3 genetic variations on susceptibility and sev 2015 Dec Juvenile idiopathic arthritis (JIA) is a chronic rheumatic disease affecting children aged less than 16 years, characterized by chronic synovitis, cartilage damage, and bony erosions mediated by matrix metalloproteinases (MMPs), mainly MMP-1 and MMP-3. The purpose of this study was to investigate MMP-1 and MMP-3 gene polymorphisms in patients with JIA, the role of genes in susceptibility to JIA, and their associations with JIA activity and prognosis. Case-control study included 100 patients diagnosed with JIA, according to the criteria of the International League of Associations for Rheumatology (ILAR), and 100 healthy children, age and sex matched, as controls. The MMP-1 (-1607 1G/2G) and MMP-3 (-1171 5A/6A) polymorphisms were screened by polymerase chain reaction-restriction fragment length polymorphism. The serum levels of MMP-1 and MMP 3 were measured by enzyme-linked immunosorbent assay. There were significant differences between patients with JIA and control groups regarding the genotype and allele frequencies distributions of both MMP-1 1G/2G and MMP-3 5A/6A polymorphisms. The haplotype 2G-6A, which carries the abnormal alleles, showed higher frequencies in patients with JIA than in controls (OD = 2.8, P = 0.002). The prevalence of MMP-1 2G and 6A allele for MMP-3 polymorphism was found to be significantly associated with persistent oligoarticular, rheumatoid factor (RF)-positive polyarthritis, and systemic JIA groups. There were significantly increased serum levels of MMP-1 and MMP-3 associated with 2G/6A haplotype in the patient group, especially with the polyarticular RF (+ve) group than in other groups and the control group. MMP-1 and MMP-3 haplotypes could be useful genetic markers for JIA susceptibility and severity in the juvenile Egyptian population. Moreover, our data further support the use of serum MMP-3 and MMP-1 as specific markers of disease activity in JIA.
27987517 [Cerebral infarction in a patient with primary Sjogren's syndrome: a case report and liter 2016 Dec 18 Sjogren's syndrome (SS) is a chronic autoimmune disorder characterized by lymphocytes infiltration in the exocrine glands. Central nervous system complications of primary SS are not rare, but ischemic stroke has been rarely reported. Here we report a 43-year-old female with a two-year history of primary SS, presenting with sudden cerebral infarction. Her primary SS was diagnosed on the basis of clinical features, high levels of serum anti-SSA and anti-SSB antibodies, salivary gland secretion evaluation and positive sublingual gland biopsy results. Magnetic resonance imaging revealed infarct lesions in the parietal and occipital lobes, as well as in the left basal ganglia. Magnetic resonance angiography showed a remarkable stenosis in the left middle cerebral artery. Other differential diagnoses were ruled out. Corticosteroid and immunosuppressor, together with anti-platelet and statin were effective, and the patient recovered quickly without sequelae. Based on these findings, vasculitis due to primary SS should be considered among the causes of stroke. The literature was reviewed and the relationship between primary SS and cerebral infarction explored. The pathogenesis of ischemic stroke in primary SS is still unknown and warrants further studies.
26540556 The CD68(+)/H-ferritin(+) cells colonize the lymph nodes of the patients with adult onset 2016 Mar In this work, we aimed to evaluate the levels of ferritin enriched in H subunits (H-ferritin) and ferritin enriched in L subunits (L-ferritin) and the cells expressing these two molecules in the lymph node (LN) biopsies obtained from adult-onset Still's disease (AOSD) patients, and the possible correlation among these data and the severity of the disease. Ten patients with AOSD underwent LN biopsy. All the samples were stained by immunofluorescence. A statistical analysis was performed to estimate the possible correlation among both H-ferritin and L-ferritin tissue expression and the clinical picture of the disease. Furthermore, the same analysis was performed to evaluate the possible correlation among the number of CD68(+)/H-ferritin(+) or CD68(+)/L-ferritin(+) cells and the clinical picture. Immunofluorescence analysis demonstrated an increased tissue H-ferritin expression in the LNs of AOSD patients. This increased expression correlated with the severity of the disease. An increased number of CD68 macrophages expressing H-ferritin was observed in the LN samples of our patients. Furthermore, we observed that the number of CD68(+)/H-ferritin(+) cells correlated significantly with the severity of the clinical picture. Our data showed an imbalance between the levels of H- and L-ferritin in LNs of AOSD patients and the evidence of an increased number of CD68(+)/H-ferritin(+) cells in the same organs. Furthermore, a correlation among both the tissue H-ferritin levels and the CD68(+)/H-ferritin(+) cells and the clinical picture was observed.
26456254 Clinical and Molecular Inflammatory Response in Sjögren Syndrome-Associated Dry Eye Patie 2016 Jan PURPOSE: To evaluate the response of the lacrimal function unit in Sjögren syndrome (SS)-associated dry eye patients exposed to 2 simulated daily life environmental conditions. DESIGN: Prospective crossover pilot study. METHODS: Fourteen female SS dry eye patients were exposed for 2 hours to a controlled normal condition (23 C, 45% relative humidity, and air flow 0.10 m/s) and a controlled adverse condition that simulates desiccating stress (23 C, 5% relative humidity, and air flow 0.10 m/s). The following dry eye tests were performed before and after the exposure: tear osmolarity, phenol red thread test, conjunctival hyperemia, fluorescein tear break-up time, corneal fluorescein staining, conjunctival lissamine green staining, and Schirmer test. Levels of 16 molecules were analyzed in tears by multiplex immunobead analysis. RESULTS: Clinical evaluation showed lacrimal functional unit impairment after the desiccating stress: significantly increased tear osmolarity (315.7 ± 3.0 vs 327.7 ± 5.1 mOsm/L, P = .03), conjunctival hyperemia (1.3 ± 0.1 vs 1.6 ± 0.1, P = .05), and corneal staining in temporal (3.5 ± 0.5 vs 4.7 ± 0.4, P = .01) and nasal (3.6 ± 0.5 vs 4.5 ± 0.5, P = .04) areas. Tear concentrations increased for interleukin-1 receptor antagonist (16 557.1 ± 4047.8 vs 31 895.3 ± 5916.5 pg/mL, P = .01), interleukin-6 (63.8 ± 20.2 vs 111.5 ± 29.6 pg/mL, P = .02), interleukin-8 (2196.1 ± 737.9 vs 3753.2 ± 1106.0 pg/mL, P = .03), and matrix metalloproteinase-9 (101 515.6 ± 37 088.4 vs 145 867.1 ± 41 651.5 pg/mL, P = .03). After the simulated normal condition, only a significant increase in nasal corneal staining (2.9 ± 0.5 vs 3.6 ± 0.5, P = .03) was observed. CONCLUSIONS: Even a short exposure to a desiccating environment can produce a significant deterioration of the lacrimal function unit in female SS dry eye patients. The often unnoticed exposure to these conditions during daily life may increase inflammatory activity rapidly, triggering an ocular surface deterioration.
26273943 [Clinical usefulness of Beta2microglobulin in patients with Primary Sjögren Syndrome]. 2015 The extraglandular manifestations and lymphoproliferative disorders are complications in pSS. There are few serological markers that they are useful in these conditions. OBJETIVES: to evaluate the usefulness of the β2microglobulin level in patients with pSS and its relation to extra glands manifestations , lymphoproliferative disorders and the presence of Rheumatoid factor (RF), serum immunoglobulins (Igs), and C3 and C4 levels. MATERIAL AND METHODS: we retrospectively studied patients with pSS , OAD and healthy controls . Ig G, Ig A and Ig M levels, serum complement C3 and C4 and RF were performed by immunoturbidimetry, and β2microglobulin protein by the ELISA technique in all patients. RESULTS: 19 patients with pSS (Group SSp), 28 patients with other autoimme diseases diferent from pSS (Group PAD) and 24 healthy controls (Group C).There was an signifcant increase of β2m values in Groups SS and OAD vs Group C (6.19 mg/dl vs. 2.53 mg/dl p<0.001) and (4.38 mg/dl vs. 2.53 mg/dl p<0.01). On the other hand, mean β2m levels in Group SS were higher than in Group OAD (6.19 vs. 4.38 mg/dl p<0.01).There was not a relationship between β2m level and Ig G, A , M ,complement levels and the presence of RF. CONCLUSION: β2m can discriminate patients with pSS from those with other autoimmune diseases and healthy subjects. Increased β2m level in pattients with pSS could reflect hyperactivation of B cells and it could be a potential marker associated with extraglandular manifestations and cell lymphoproliferative disorders.
27977588 Clinical characteristics of immune thrombocytopenia associated with autoimmune disease: A 2016 Dec To clarify clinical characteristics of immune thrombocytopenia (ITP) subsets associated with autoimmune diseases (AIDs).Five thousand five hundred twenty patients were reviewed retrospectively. One hundred four ITP patients were included for analysis. Clinical manifestations at first thrombocytopenic episode were recorded.Systemic lupus erythematosus (SLE) and primary Sjogren syndrome (pSS) accounted for a large part in AIDs associated with secondary ITP. SLE-ITP, pSS-ITP, and primary ITP (pITP) patients were different in several aspects in clinical and immunological characteristics. A subgroup of patients in pITP patients with some obvious autoimmune features (defined as AIF-ITP) such as positive ANA but failing to meet the diagnosis criteria now used for a specific kind of connective tissue diseases were also different with other pITP patients in some immunological features, indicating the difference in the pathogenesis mechanism of those autoimmune featured ITP patients.ITP patients were heterogeneous in clinical characteristics. Further study about the different pathogenesis of ITP subsets especially those AIF-ITP patients who only presented with thrombocytopenia will help us have a better understanding of pathogenesis of ITP and a better management of ITP patients.
27538522 Elevated level of circulating CD4(+)Helios(+)FoxP3(+) cells in primary Sjogren's syndrome 2017 Jul OBJECTIVE: This study was designed to investigate the expression of regulatory T cells in primary Sjögren's Syndrome (pSS) and to evaluate the clinical role of CD4 (+) Helios(+) FoxP3(+) cells in pSS patients. METHODS: CD4 (+) FoxP3(+ )T cells in the peripheral blood of 39 pSS patients and 30 healthy controls were measured by flow cytometry and CD25 and Helios expression were also analyzed. The repression ability of CD4 (+) CD25(hi) cells was tested in vitro. Clinical information of pSS patients was retrospectively collected and their correlations with circulating Treg cells were analyzed. Cytokine levels in plasma were measured by ELISA and correlations with Helios(+) FoxP3(+ )cells were also detected. RESULTS: Circulating FoxP3(+ )and Helios(+) FoxP3(+ )cells were elevated in pSS patients compared with controls. The suppression function of CD4 (+) CD25(hi) cells is not different between two groups. There are inverse correlations between Helios(+) FoxP3(+ )percentage and ESR, IgG, IgM and ESSDAI. Anti-SSB(-) patients possess higher level of Helios(+) FoxP3(+ )cells than anti-SSB(+ )patients. IL-6, IFNγ and IFNα levels were increased in pSS plasma and there were positive correlations between the levels of IFNγ/IFNα and percentage of Helios(+) FoxP3(+ )cells. CONCLUSION: Circulating Helios (+) FoxP3(+) cells were elevated in pSS patients and may contribute to suppressing autoimmunity in pSS patients.
26613867 Elevated Plasma P-Selectin Autoantibodies in Primary Sjögren Syndrome Patients with Throm 2015 Nov 28 BACKGROUND Primary Sjögren's syndrome (pSS) is one of the most common chronic systemic autoimmune diseases, and thrombocytopenia is one of the hematological manifestations of pSS. When platelet and endothelial cells are activated, P-selectin is expressed on the cell surface. This study aimed to investigate the role of P-selectin autoantibodies in the pathogenesis of thrombocytopenia in pSS. MATERIAL AND METHODS P-selectin autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 38 pSS patients without thrombocytopenia and 32 pSS patients with thrombocytopenia, 32 idiopathic thrombocytopenic purpura (ITP) patients, and 35 healthy controls. RESULTS The plasma P-selectin autoantibodies (A490) in ITP patients and pSS patients with/without thrombocytopenia were significantly higher than those in healthy controls, but there were no significant differences between ITP patients and pSS patients with thrombocytopenia. The positive rate of P-selectin autoantibodies in pSS patients with thrombocytopenia was significantly higher than that in ITP patients. The platelet count was lower in P-selectin autoantibodies-positive patients, while among pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients than in P-selectin autoantibodies-negative patients. In ITP patients and pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients. CONCLUSIONS Elevated plasma P-selectin autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS patients.
26345947 Role of autoantibodies to various Ro60 epitopes in the decrease of lymphocytes seen in sys 2015 Aug 21 We investigated the roles of autoantibodies to different Ro60 epitopes in lymphopenia in systemic lupus erythematosus (SLE) and primary Sjögren's syndrome (pSS). We recruited 16 patients with SLE, 14 with pSS, and 10 healthy controls; all were female. Patients had active disease, had not received glucocorticoid or immunosuppressants for at least 3 months, and had positive laboratory tests for autoantibodies against Ro60. Patient peripheral blood lymphocyte (LC) counts were < 1 x 10(9)/L: (0.66 ± 0.12) x 10(9)/L and (0.70 ± 0.16) x 10(9)/L for SLE and pSS groups, respectively (P = 0.511). LCs from each group were cultured in vitro with each of the three immunotoxins (ITs) (AE1-3), which specifically combine with one of the three epitopes (aa482-493, aa310-323, and aa230-241, respectively) on Ro60. The cytotoxicity of each IT to the cultured LCs was measured by the MTT colorimetric method. The relationships between IT cytotoxicity and LC counts were analyzed, and autoantibodies against the three epitopes in patient peripheral blood were detected. All ITs showed cytotoxicity to control LCs; however, AE3 and AE2 showed greater toxicity to LCs from SLE and pSS groups, respectively, and the enhanced cytotoxicity was significantly associated with the respective LC counts (r = 0.653, P = 0.06; r = 0.594, P = 0.025). No difference was found in the prevalence of the autoantibodies between the SLE and pSS groups. These results suggest that autoantibodies to Ro60 might play a pathogenic role in lymphopenia in both SLE and pSS, but the pathogenic mechanisms might differ.
26317390 Neutrophilic Epitheliotropism is a Histopathological Clue to Neutrophilic Urticarial Derma 2016 Jan BACKGROUND: Neutrophilic urticarial dermatosis (NUD) comprises a particular autoinflammatory condition within the spectrum of aseptic neutrophilic dermatoses characterized by a distinct urticarial eruption clinically and a neutrophilic dermatosis histopathologically. OBJECTIVE: In this study, we reviewed skin biopsies of lesional skin of patients seen in our outpatient clinic for autoimmune dermatoses and in allergy department from 1982 to 2014 that fulfilled these criteria. METHODS: A total of 77 biopsies from 50 patients were analyzed histopathologically. Included were cases of Schnitzler syndrome, Still disease, systemic lupus erythematosus, Sjögren syndrome, cryopyrin-associated periodic syndrome, primary biliary cirrhosis, inflammatory bowel disease, and those that had signs of systemic inflammation not otherwise specified, that is, fever, arthritis, leukocytosis, and elevated erythrocyte sedimentation rate. A control cohort was defined as including a total of 70 biopsies from 50 patients comprising neutrophilic urticaria (pressure-induced and not pressure-induced), conventional urticaria, lupus erythematosus expressing neutrophils, and exanthematous drug reaction of macular type expressing neutrophils. RESULTS: Skin biopsies of NUD revealed a perivascular and interstitial neutrophilic infiltrate focally extending into the epithelia of epidermis, hair follicles, sebaceous and sweat glands, a feature which we termed neutrophilic epitheliotropism. This neutrophilic epitheliotropism proved to be of high sensitivity (83.1%) and lower specificity (74.3%). The histological findings could be substantiated by immunohistochemical markers for leukocytes (elastase and myeloperoxidase), in particular in cases where neutrophils showed uncharacteristic band-like nuclei. CONCLUSIONS: Neutrophilic epitheliotropism is a new sensitive and specific histopathological clue for NUD, a histopathological reaction pattern within the spectrum of neutrophilic dermatoses that needs to be differentiated from conventional urticaria.
27381477 Targeting the Ca(2+) Sensor STIM1 by Exosomal Transfer of Ebv-miR-BART13-3p is Associated 2016 Aug Primary Sjögren's syndrome (pSS) is a systemic autoimmune disease that is associated with inflammation and dysfunction of salivary and lacrimal glands. The molecular mechanism(s) underlying this exocrinopathy is not known, although the syndrome has been associated with viruses, such as the Epstein Barr Virus (EBV). We report herein that an EBV-specific microRNA (ebv-miR-BART13-3p) is significantly elevated in salivary glands (SGs) of pSS patients and we show that it targets stromal interacting molecule 1 (STIM1), a primary regulator of the store-operated Ca(2+) entry (SOCE) pathway that is essential for SG function, leading to loss of SOCE and Ca(2+)-dependent activation of NFAT. Although EBV typically infects B cells and not salivary epithelial cells, ebv-miR-BART13-3p is present in both cell types in pSS SGs. Importantly, we further demonstrate that ebv-miR-BART13-3p can be transferred from B cells to salivary epithelial cells through exosomes and it recapitulates its functional effects on calcium signaling in a model system.
25056402 Frequent involvement of central nervous system in primary Sjögren syndrome. 2015 Feb Primary Sjögren syndrome (pSS) is a systemic autoimmune disease characterized by lymphocytic infiltration of the salivary and tear glands, and autoantibody secretion, in the absence of other systemic autoimmune disorder. Among autoimmune diseases, it is a relatively common disease, but the burden of central nervous system (CNS) involvement is controversial. This retrospective study evaluates the prevalence, clinical patterns and outcomes of CNS involvement in a cohort of patients with primary Sjögren syndrome. We evaluated 93 patients with pSS diagnosed according to American-European Consensus Group criteria. Fourteen patients (15.1 %) had CNS involvement. All were women with an average age of onset of the disease of 42.1 ± 14.7 years (average ± SD) and an average age of onset of neurological involvement of 47.29 ± 16 years. Three had parkinsonian syndrome, two epilepsy, two motor and sensory deficits, two headache with brain magnetic resonance abnormalities, two neuromyelitis optica, two chronic progressive myelitis and one aseptic meningitis. Neurological involvement preceded Sjögren syndrome diagnosis in nine of the patients (64 %), and neurological outcome was good in 11 patients (78.6 %). Central nervous involvement was not as rare as expected, and the frequency was similar to the frequency of peripheral nervous system involvement. In half of the patients, this was the first symptom of the disease, emphasizing the importance of considering this diagnosis, especially in young female with neurological symptoms without other evident cause.
26630293 Paeoniflorin ameliorates symptoms of experimental Sjogren's syndrome associated with down- 2016 Jan Paeoniflorin (PF), an active compound extracted from Paeony root, has been used in therapy of autoimmune diseases with effective clinical efficiency and higher safety. Sjogren's syndrome (SS) is a chronic, systemic, immune-mediated inflammatory disease. In this study, we demonstrated that novel pro-inflammatory factor Cyr61/CCN1 was up-regulated in epithelial cells of salivary glands of primary SS patients and submandibular gland autoantigen-induced experimental SS mice. Blocking Cyr61 expression with special monoclonal antibody improved saliva secretion by ameliorating inflammatory infiltration and cytokines production in vivo. Furthermore, we showed that PF could alleviate inflammation by down-regulating Cyr61 expression in experimental SS mice. In conclusion, our new findings revealed for the first time that Cyr61 involves the pathogenesis of primary SS and PF alleviates SS-like symptoms associated with inhibiting Cyr61 expression, providing new insights into the potential molecular mechanism of PF in primary SS treatment.
25433020 Systemic activity and mortality in primary Sjögren syndrome: predicting survival using th 2016 Feb OBJECTIVE: To score systemic activity at diagnosis and correlate baseline activity with survival in a large cohort of patients with primary Sjögren syndrome (SS). PATIENTS AND METHODS: We include 1045 consecutive patients who fulfilled the 2002 classification criteria for primary SS. The clinical and immunological characteristics and level of activity (EULAR-SS Disease Activity Index (ESSDAI) scores) were assessed at diagnosis as predictors of death using Cox proportional hazards regression analysis adjusted for age at diagnosis. The risk of death was calculated at diagnosis according to four different predictive models. RESULTS: After a mean follow-up of 117 months, 115 (11%) patients died. The adjusted standardised mortality ratio for the total cohort was 4.66 (95% CI 3.85 to 5.60), and survival rates at 5, 10, 20 and 30 years were 96%, 90%, 81% and 60%, respectively. The main baseline factors associated with overall mortality in the multivariate analysis were male gender, cryoglobulins and low C4 levels. Baseline activity in the constitutional, pulmonary and biological domains was associated with a higher risk of death. High activity in at least one ESSDAI domain (HR 2.14), a baseline ESSDAI score ≥14 (HR 1.85) and more than one laboratory predictive marker (lymphopenia, anti-La, monoclonal gammopathy, low C3, low C4 and/or cryoglobulins) (HR 2.82) were associated with overall mortality; these HRs increased threefold to 10-fold when the analysis was restricted to mortality associated with systemic disease. CONCLUSIONS: Patients with primary SS, who present at diagnosis with high systemic activity (ESSDAI ≥14) and/or predictive immunological markers (especially those with more than one), are at higher risk of death.
26126608 Use of RNA sequencing to evaluate rheumatic disease patients. 2015 Jul 1 Studying the factors that control gene expression is of substantial importance for rheumatic diseases with poorly understood etiopathogenesis. In the past, gene expression microarrays have been used to measure transcript abundance on a genome-wide scale in a particular cell, tissue or organ. Microarray analysis has led to gene signatures that differentiate rheumatic diseases, and stages of a disease, as well as response to treatments. Nowadays, however, with the advent of next-generation sequencing methods, massive parallel sequencing of RNA tends to be the technology of choice for gene expression profiling, due to several advantages over microarrays, as well as for the detection of non-coding transcripts and alternative splicing events. In this review, we describe how RNA sequencing enables unbiased interrogation of the abundance and complexity of the transcriptome, and present a typical experimental workflow and bioinformatics tools that are often used for RNA sequencing analysis. We also discuss different uses of this next-generation sequencing technology to evaluate rheumatic disease patients and investigate the pathogenesis of rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, juvenile idiopathic arthritis and Sjögren's syndrome.
26636371 Energy-Based Pharmacophore and Three-Dimensional Quantitative Structure--Activity Relation 2016 Jan 25 Silent mating-type information regulation 2 homologue 1 (SIRT1), being the homologous enzyme of silent information regulator-2 gene in yeast, has multifaceted functions. It deacetylates a wide range of histone and nonhistone proteins; hence, it has good therapeutic importance. SIRT1 was believed to be overexpressed in many cancers (prostate, colon) and inflammatory disorders (rheumatoid arthritis). Hence, designing inhibitors against SIRT1 could be considered valuable. Both structure-based and ligand-based drug design strategies were employed to design novel inhibitors utilizing high-throughput virtual screening of chemical databases. An energy-based pharmacophore was generated using the crystal structure of SIRT1 bound with a small molecule inhibitor and compared with a ligand-based pharmacophore model that showed four similar features. A three-dimensional quantitative structure-activity relationship (3D-QSAR) model was developed and validated to be employed in the virtual screening protocol. Among the designed compounds, Lead 17 emerged as a promising SIRT1 inhibitor with IC50 of 4.34 μM and, at nanomolar concentration (360 nM), attenuated the proliferation of prostate cancer cells (LnCAP). In addition, Lead 17 significantly reduced production of reactive oxygen species, thereby reducing pro inflammatory cytokines such as IL6 and TNF-α. Furthermore, the anti-inflammatory potential of the compound was ascertained using an animal paw inflammation model induced by carrageenan. Thus, the identified SIRT1 inhibitors could be considered as potent leads to treat both cancer and inflammation.
27900348 Implementation of musculoskeletal ultrasonography in detection of early juvenile idiopathi 2016 AIM: To determine whether early clinical, laboratory and musculoskeletal ultrasound (MSUS) characteristics can be used as early detectors of juvenile idiopathic arthritis. PATIENTS AND METHODS: Forty (40) patients with juvenile idiopathic arthritis (JIA) diagnosed according to the ILAR criteria [1] and 20 healthy control children. All patients were subjected to the following assessment at base line and at follow up after 6 months: Clinical evaluation, MSUS examination and laboratory evaluation. RESULTS: Of the 40 patients, 6 patients (15%) had systemic onset subtype, 8 (20%) oligoarticular extended, 9 (22.5%) oligoarticular persistent, 5 (12.5%) polyarticular rheumatoid factor (RF) +ve, 6 (15%) polyarticular RF -ve, 5 (12.5%) enthesitis related subtype and only one patient (2.5%) had psoriatic JIA. MSUS detected more synovitis than clinical examination (subclinical synovitis) both at base line and at follow up. MSUS is highly sensitive for early detection of joint involvement in JIA when compared to physical examination. Significant decrease in the mean cartilage thickness of the patients measured at follow up as compared to measures at base line. CONCLUSION: MSUS is highly sensitive for early detection of joint involvement in JIA when compared to physical examination.