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ID PMID Title PublicationDate abstract
25557346 Potentially pathogenic immune cells and networks in apparently healthy lacrimal glands. 2015 Jan Lacrimal glands of people over 40 years old frequently contain lymphocytic infiltrates. Relationships between histopathological presentation and physiological dysfunction are not straightforward. Data from rabbit studies have suggested that at least two immune cell networks form in healthy lacrimal glands, one responding to environmental dryness, the other to high temperatures. New findings indicate that mRNAs for several chemokines and cytokines are expressed primarily in epithelial cells; certain others are expressed in both epithelial cells and immune cells. Transcript abundances vary substantially across glands from animals that have experienced the same conditions, allowing for correlation analyses, which detect clusters that map to various cell types and to networks of coordinately functioning cells. A core network--expressing mRNAs including IL-1α, IL-6, IL-17A, and IL-10--expands adaptively with exposure to dryness, suppressing IFN-γ, but potentially causing physiological dysfunction. High temperature elicits concurrent increases of mRNAs for prolactin (PRL), CCL21, and IL-18. PRL is associated with crosstalk to IFN-γ, BAFF, and IL-4. The core network reacts to the resulting PRL-BAFF-IL-4 network, creating a profile reminiscent of Sjögren's disease. In a warmer, moderately dry setting, PRL-associated increases of IFN-γ are associated with suppression of IL-10 and augmentations of IL-1α and IL-17, creating a profile reminiscent of severe chronic inflammation.
25320221 Role of fractalkine in the pathogenesis of primary Sjögren syndrome: increased serum leve 2014 Dec OBJECTIVE: To investigate the expression of fractalkine and identify the clinical effects of fractalkine and its receptor (CX3CR1) in patients with primary Sjögren syndrome (pSS). METHODS: Serum fractalkine levels were determined by ELISA. Immunohistochemical staining was done to compare the expression of fractalkine and CX3CR1 between salivary glands (SG) of patients with SS and controls. The cells to be merged with fractalkine were evaluated by confocal microscopy. Type of CX3CR1-expressing cells among infiltrating lymphocytes in SG was analyzed by confocal microscopy. Further, associations among fractalkine, proinflammatory cytokines, and clinical profiles were investigated. RESULTS: Serum fractalkine levels in patients with pSS were higher than those in the control group (p = 0.026). SG expression of fractalkine and its receptor was upregulated in patients with pSS compared to that in the controls by immunohistochemistry. Higher histological grade was associated with more fractalkine-positive cells per total epithelial cells. Epithelial cells were the main fractalkine-expressing cell type in the SG. Serum fractalkine levels were significantly correlated with proinflammatory cytokines levels (interleukin 17: r = 0.685, p = 0.029; tumor necrosis factor-α: r = 0.444, p = 0.003), antinuclear antibody (r = 0.349, p = 0.022), and immunoglobulin G levels (r = 0.325, p = 0.044). Serum fractalkine levels in patients with extraglandular manifestations of pSS were significantly higher than in those without extraglandular manifestations (p = 0.026). CONCLUSION: Fractalkine and CX3CR1 may play a role in the pathogenesis of pSS, including extraglandular manifestations.
24670136 The clinical characteristics of patients with IgG4-related disease with infiltration of th 2014 Nov OBJECTIVES: Mikulicz's disease (MD) is an immunoglobulin (Ig) G4-related disease with systemic symptoms. Submandibular gland (SMG) biopsy is recommended for patients with possible IgG4-related MD for accurate differential diagnosis; however, it is difficult for certain patients to undergo this procedure. In contrast, labial salivary gland (LSG) biopsy is more convenient. Here we present an analysis of patients with IgG4-related MD whose LSG specimens were infiltrated with abundant IgG4-positive plasma cells. METHODS: Sixteen patients diagnosed with IgG4-related MD underwent simultaneous SMG and LSG biopsies. We evaluated patients' serological and (18)F-fluoro-2-deoxyglucose-positron emission tomography/computed tomography ((18)F-FDG-PET/CT) and grouped them as LSG+ (LSG specimens with > 40% IgG4-positive plasma cells/IgG-positive plasma cells, 11 patients) or LSG- (LSG specimens with < 40% IgG4-positive plasma cells/IgG-positive plasma cells, 6 patients). RESULTS: There were not significant differences in serum IgG and IgG4 levels between the two groups; however, serum concentrations of soluble interleuikin-2 receptor (sIL-2R) were significantly higher in the LSG+ group. All patients with increased (18)F-FDG uptake in their parotid glands were a part of the LSG+ group. CONCLUSIONS: When a SMG biopsy is not possible, the serum concentration of sIL-2R and (18)F-FDG-PET/CT findings may predict whether LSG biopsy will facilitate the diagnosis of IgG4-related MD.
23827249 Autoinflammatory syndromes. 2013 Jul Autoinflammatory syndromes comprise a diagnostically challenging group of systemic inflammatory disorders uniquely related by (1) dysregulation of innate immunity, (2) inflammasome activation, (3) dramatic clinical features (high fevers, neutrophilic rashes, and bone or synovial involvement), (4) impressive acute phase responses, and (5) effective treatment with cytokine inhibitors. This review details some of the more common autoinflammatory disorders, their distinguishing features and dermatologic manifestations, and how an accurate diagnosis can be established in patients presenting with periodic or intermittent febrile disorders.
23441777 The frequency of sicca symptoms and Sjögren's syndrome in patients with systemic sclerosi 2013 Feb OBJECTIVE: The objectives are to detect the frequency of sicca symptoms and Sjögren's syndrome (SS) in patients with systemic sclerosis (SSc) based on the diagnostic criteria of the American-European Consensus Group (AECG) and to evaluate demographic, clinical and serologic characteristics. PATIENTS AND METHOD: One hundred and eighteen SSc patients referred to our hospital were included in this study. All SSc patients were questioned with respect to sicca symptoms. Levels of rheumatoid factor (RF), anti-nuclear antibodies (ANA), anti-Ro and anti-La antibodies were measured; non-stimulated saliva amounts were recorded and Schirmer test and break-up time were applied to all patients. Minor salivary gland biopsy samples were obtained from those patients giving ≥ 3 positive answers to sicca symptom questions, patients with positive xerostomia/xerophthalmia test results, and patients with at least one antibody being positive. Patients presenting with grade 3 and/or grade 4 sialoadenitis based on Chisholm criteria were considered pathological. RESULTS: Sicca symptoms were present in 84 of 118 patients with SSc (71.2%). Minor salivary gland biopsy samples were obtained from 74 patients. Grade 3 and/or grade 4 sialoadenitis was detected in 40 (33.9%) patients and they were diagnosed with SS. Compared to patients diagnosed with SSc alone, systemic sclerosis patients diagnosed with SS had lower pulmonary hypertension and less diffuse lung involvement. Statistically significant difference was detected in terms of sclerodactylia and telangiectasia between SSc-SS and SSc patient groups (P = 0.045 and P = 0.011, respectively). Serological assessments revealed that in the SSc-SS group, 13 patients were anti-Ro antibody positive, six were anti-La antibody positive and 37 were anti-topoisomerase 1 antibody positive. RF, ANA and anti-centromere antibody levels were higher in the SSc-SS group. CONCLUSION: In the present study, highly frequent sicca symptoms and Sjögren's syndrome based on AECG criteria were noted in patients with systemic sclerosis. The SSc-SS patient group had less severe clinical course and lung involvement.
22906617 The spectrum of immune-mediated autonomic neuropathies: insights from the clinicopathologi 2013 Jan Although autonomic neuropathy may occur as a secondary consequence of various diseases, other patients without any obvious underlying diseases show profound autonomic dysfunctions from the early phase of the disease. These idiopathic or primary cases are divided into pure autonomic neuropathy, autonomic neuropathy with sensory impairment, and autonomic neuropathy with sensory and motor impairment based on the concomitance or absence of sensory or motor dysfunctions. The discovery of the antiganglionic acetylcholine receptor antibody suggested the involvement of immune mechanisms in idiopathic cases, especially in those cases with pure autonomic neuropathy. The ability to test for the presence of this antibody has significantly expanded the concept of autonomic neuropathy to include cases with a chronic progressive course that mimics pure autonomic failure. Recent work based on the antiganglionic acetylcholine receptor antibody has established autoimmune autonomic ganglionopathy as an isolated nosological entity. Other forms of primary autonomic neuropathies include acute autonomic and sensory neuropathy and acute autonomic sensory and motor neuropathy, although the nosological relationship of the latter to Guillain-Barré syndrome should be discussed. Although the possibility of infectious, metabolic or toxic aetiologies should be carefully excluded in these forms of autonomic neuropathy, the monophasic clinical course and the presence of antecedent infections suggest the involvement of immune mechanisms similar to Guillain-Barré syndrome. Neuronopathy in the autonomic ganglia is considered to be a common pathology in these autonomic neuropathies. In addition, clinically significant autonomic neuropathy may be associated with pre-existing immunological diseases such as paraneoplastic syndrome and Sjögren's syndrome. An overlap with autoimmune autonomic ganglionopathy has been suggested in these settings.
23153784 Subtalar joint septic arthritis in a patient with hypogammaglobulinemia. 2013 Mar The clinical presentation of a monoarticular, red, hot, and swollen joint has many possible diagnoses, including septic arthritis, which is 1 of the most devastating. The morbidity associated with this pathologic process involves permanent joint damage and the potential for progression to systemic illness and, even, mortality. The common risk factors for joint sepsis include a history of rheumatoid arthritis, previous joint surgery, joint prosthesis, intravenous drug abuse, alcoholism, diabetes, previous intra-articular steroid use, and cutaneous ulceration. The diagnosis is primarily determined from the culture results after arthrocentesis and correlation with direct visualization, imaging, and various serologies, including synovial analysis. In the present report, a case of an insidious presentation of subtalar joint septic arthritis and its association with a unique patient presentation concomitant with primary immunodeficiency and culture-proven Myocplasma hominis infection is discussed. Septic arthritis has a predilection for the lower extremities and typically is isolated to the hip or knee, with less common involvement of the ankle or metatarsophalangeal joints. Owing to the uncommon nature of primary immunodeficiency disorders and the paucity of studies discussing their association with septic arthridites, we aimed to raise awareness of subtalar joint septic arthritis and to provide a brief overview of the pathogenesis as it presented in a 33-year-old male with X-linked hypogammaglobulinemia/agammaglobulinema.
25856943 Hypermobility syndrome. 2014 Aug Three cases of Hypermobility Syndrome (HS) are discussed. The first case was a young female, aged 24, with musculoskeletal symptoms since 5 years. Second was an 18 year old male with similar symptoms since 3 years. The third was an elderly female who presented with knee joint osteoarthritis (OA) and apparent but reducible deformities of hands mimicking rheumatoid arthritis (RA). All three patients had hypermobility of joints in absence of demonstrable systemic rheumatic disease. The prevalence, clinical features and management of the entity is discussed. An increased awareness of this condition among physicians is warranted as some patients may be erroneously diagnosed as RA/SLE and may be put on DMARDs and steroids.
25143870 G protein signaling modulator-3: a leukocyte regulator of inflammation in health and disea 2014 G protein signaling modulator-3 (GPSM3), also known as G18 or AGS4, is a member of a family of proteins containing one or more copies of a small regulatory motif known as the GoLoco (or GPR) motif. GPSM3 interacts directly with Gα and Gβ subunits of heterotrimeric G proteins to regulate downstream intracellular signals initiated by G protein coupled receptors (GPCRs) that are activated via binding to their cognate ligands. GPSM3 has a selective tissue distribution and is highly expressed in immune system cells; genome-wide association studies (GWAS) have recently revealed that single nucleotide polymorphisms (SNPs) in GPSM3 are associated with chronic inflammatory diseases. This review highlights the current knowledge of GPSM3 function in normal and pathologic immune-mediated conditions.
25268598 The role of TNF inhibitors in psoriatic disease. 2014 Jun In contrast to many other diseases, modern psoriasis therapy has a fairly brief history. Until about 15 years ago, clinicians and their patients had few options, with limited ability to rein in the disease process.The success of antifolate methotrexate in the treatment of rheumatoid arthritis (RA) led to clinical evaluation and adoption of the agent, a principal form of treatment for psoriasis, which, like RA, has its origin based in inflammation. The introduction of tumor necrosis factor-α inhibitors marked the beginning of the biologic era of psoriasis therapy. Also borrowed from the field of rheumatology, biologic therapy has evolved from improved understanding of the molecular basis of the disease process. An increased recognition of comorbid conditions that often accompany psoriasis, particularly psoriatic arthritis, can complicate clinical management. Dermatologists and other clinicians who treat psoriasis continue to benefit from insights gained in the field of rheumatology.
24010407 A multilectin affinity approach for comparative glycoprotein profiling of rheumatoid arthr 2013 Sep 6 BACKGROUND: Arthritis refers to inflammation of joints and includes common disorders such as rheumatoid arthritis (RA) and spondyloarthropathies (SpAs). These diseases differ mainly in terms of their clinical manifestations and the underlying pathogenesis. Glycoproteins in synovial fluid might reflect the disease activity status in the joints affected by arthritis; yet they have not been systematically studied previously. Although markers have been described for assisting in the diagnosis of RA, there are currently no known biomarkers for SpA. MATERIALS AND METHODS: We sought to determine the relative abundance of glycoproteins in RA and SpA by lectin affinity chromatography coupled to iTRAQ labeling and LC-MS/MS analysis. We also used ELISA to validate the overexpression of VCAM-1, one of the candidate proteins identified in this study, in synovial fluid from RA patients. RESULTS AND DISCUSSION: We identified proteins that were previously reported to be overexpressed in RA including metalloproteinase inhibitor 1 (TIMP1), myeloperoxidase (MPO) and several S100 proteins. In addition, we discovered several novel candidates that were overexpressed in SpA including Apolipoproteins C-II and C-III and the SUN domain-containing protein 3 (SUN3). Novel molecules found overexpressed in RA included extracellular matrix protein 1 (ECM1) and lumican (LUM). We validated one of the candidate biomarkers, vascular cell adhesion molecule 1 (VCAM1), in 20 RA and SpA samples using ELISA and confirmed its overexpression in RA (p-value <0.01). Our quantitative glycoproteomic approach to study arthritic disorders should open up new avenues for additional proteomics-based discovery studies in rheumatological disorders.
24738849 Immune regulation and anti-inflammatory effects of isogarcinol extracted from Garcinia man 2014 May 7 Isogarcinol is a natural compound that we extracted from Garcinia mangostana L., and we were the first to report that it is a new immunosuppressant. In the present study, we investigated the immune regulation and anti-inflammatory effects of isogarcinol on collagen-induced arthritis (CIA) and explored its potential mechanism in the treatment of rheumatoid arthritis. The oral administration of isogarcinol significantly reduced clinical scores, alleviated cartilage and bone erosion, and reduced the levels of serum inflammatory cytokines in CIA mice. Isogarcinol inhibited xylene-induced mouse ear edema in vivo. In vitro, isogarcinol decreased iNOS and COX-2 mRNA expression and NO content by inhibiting NF-κB expression. Furthermore, isogarcinol decreased the activity of NFAT and inhibited IL-2 expression. The mechanism of action of isogarcinol is associated with down-regulation of both autoimmune and inflammatory reactions.
23505550 Prevention of arthritis by locally synthesized recombinant antibody neutralizing complemen 2013 Treatment of patients suffering from chronic diseases such as rheumatoid arthritis with recombinant antibodies is time consuming and fairly expensive and can be associated with side effects due to generalized depletion of the target molecule. We have addressed these issues by developing an alternative approach consisting of the intraarticular injection of a DNA vector encoding for the anti-C5 neutralizing recombinant miniantibody MB12/22. This method allows local production of the antibody in sufficient amount to be effective in preventing joint inflammation in a rat model of antigen-induced arthritis. Injection of the DNA vector in a right knee of normal rats resulted in the production of the minibody detected in the synovial washes by western blot with a strong signal peaking at 3 days after administration. DNA encoding for the minibody was shown for 14 days in the synovial tissue and was undetectable in the controlateral knee and in other organs. The preventive effect of this approach was evaluated in rats receiving a single injection of the vector 3 days before the induction of antigen-induced arthritis and analyzed 3 days later. The treated rats exhibited a lower increase in swelling, associated with a lower number of PMN in the articular washes and reduced deposition of C9 in synovial tissue compared to control rats. These results suggest that treating the inflamed joints with a vector that induces a local production of a neutralizing anti-C5 antibody may represent a useful strategy to inhibit in situ complement activation and to treat patients with monoarthritis. Moreover, this approach may be adopted as a novel therapeutic strategy to prevent monoarthritis as an alternative to local treatment with antibodies commonly used in this form of arthritis, with the advantages of the lower cost and the longer persistence of antibody production.
24657018 Recommendations for the coordinated management of psoriatic arthritis by rheumatologists a 2014 Apr Psoriatic arthritis, a chronic inflammatory musculoskeletal disease that is associated with psoriasis, causes joint erosions, accompanied by loss of function and quality-of-life. The clinical presentation is variable, with extreme phenotypes that can mimic rheumatoid arthritis or ankylosing spondylitis. Because psoriasis usually presents before psoriatic arthritis, the dermatologist plays a key role in early detection of the latter. As many treatments used in psoriasis are also used in psoriatic arthritis, treatment recommendations should take into consideration the type and severity of both conditions. This consensus paper presents guidelines for the coordinated management of psoriatic arthritis by rheumatologists and dermatologists. The paper was drafted by a multidisciplinary group (6rheumatologists, 6dermatologists, and 2epidemiologists) using the Delphi method and contains recommendations, tables, and algorithms for the diagnosis, referral, and treatment of patients with psoriatic arthritis.
23218811 Arthritis: its prevalence, risk factors, and association with cardiovascular diseases in t 2013 Feb OBJECTIVE: Arthritis is associated with cardiovascular diseases (CVDs). However, there are limited epidemiologic studies on arthritis in a national survey study. We therefore investigated the prevalence of self-reported arthritis and its association with CVDs. METHODS: Data from 15,888 subjects aged 40 years or older in the United States National Health and Nutrition Examination Survey 1999 through 2008 were analyzed. CVD was defined as a self-reported history of heart attack, congestive heart failure, coronary heart disease, angina, or stroke. RESULTS: The overall prevalence of self-reported arthritis in subjects aged 40 years or older increased from 33.5% in 1999 through 2000 to 37.0% in 2007 through 2008 (P for trend = 0.017). Among subjects with arthritis in 1999 through 2008, 35.3% had osteoarthritis (OA), 17.9% had rheumatoid arthritis (RA), and 10.2% had other types of arthritis, but 36.6% were unaware of their type of arthritis. Compared with subjects without OA, subjects with OA had higher odds for CVDs (odds ratio [OR], 1.53; P < .001), especially angina (OR, 2.18: P < .001). Compared with subjects without RA, subjects with RA had higher odds for CVDs (adjusted OR, 2.39; P < .001), especially congestive heart failure (OR, 3.59; P < .001). CONCLUSIONS: Both RA and OA are strongly associated with CVDs in the general population. Further studies are needed to investigate their causal relationship.
24820470 Diagnosis of Chlamydia trachomatis in patients with reactive arthritis and undifferentiate 2014 May 14 INTRODUCTION: There is a paucity of information on the frequency of Chlamydia trachomatis-induced reactive arthritis (ReA) and undifferentiated spondyloarthropathy (uSpA) in India. In this study, arthritic patients suffering from ReA, uSpA, and rheumatoid arthritis (RA) were screened to investigate the presence of C. trachomatis infection in the synovial fluid (SF) or serum by molecular and non-molecular methods. METHODOLOGY: A total of 76 arthritic patients with ReA (n = 16) and uSpA (n = 22) composed the study group while those with RA (n = 38) served as controls. The detection of C. trachomatis DNA was done by semi-nested PCR (snPCR) and nested PCR (nPCR) targeting two different genes of C. trachomatis, namely major outer membrane protein and plasmid, respectively. The presence of serum or SF immunoglobulin IgG and IgA antibodies against C. trachomatis was studied by commercial enzyme-linked immunosorbent assay kits. RESULTS: The SF from 9 of 38 (23.6%) patients (5 with ReA and 4 with uSpA) was positive for at least one C. trachomatis DNA by snPCR or nPCR in comparison to RA (1/38 [2.6%]; p value < 0.05). There was no correlation between the snPCR or nPCR and the serological results of patients with ReA or uSpA. CONCLUSIONS: As molecular diagnostic techniques established intra-articular C. trachomatis infection among this group of seronegative spondyloarthropathies in India, these findings should be viewed with concern, and snPCR or nPCR should be considered for a more reliable diagnosis.
22764042 MRI versus conventional measures of disease activity and structural damage in evaluating t 2013 Mar OBJECTIVE: To compare the American College of Rheumatology paediatric (ACRp) response criteria and conventional radiography with MRI findings in a cohort of patients with juvenile idiopathic arthritis. METHODS: Forty consecutive patients (30 girls, 10 boys; median age 10.8 years) with arthritis of the wrist starting treatment with disease-modifying antirheumatic drugs or biological agents were recruited. At 1-year follow-up the treatment response was assessed by ACRp criteria and radiographic progression using the adapted Sharp/van der Heijde method. Wrist MRIs were evaluated using both the paediatric-MRI and the OMERACT rheumatoid arthritis MRI scores. Sensitivity to change of clinical and imaging variables was assessed by standardised response mean (SRM) and relative efficiency (RE) was used to compare SRMs. RESULTS: ACRp90 responders showed a significantly higher decrease in MRI synovitis score (median change -4) than non-responders (median change 0), ACRp30-50 responders (median change 0) and ACRp70 responders (median change -1) (p=0.0006, Kruskal-Wallis test). Non-responders showed significantly higher radiographic progression than ACRp90 responders (pB=0.016). The MRI synovitis score showed a greater responsiveness to change (SRM 1.69) compared with the majority of ACR core set of variables. MRI erosion scores were less responsive than conventional radiography in detecting destructive changes (RE <1). MRI follow-up revealed no signs of inflammation in four out of 24 wrists with clinically inactive disease. CONCLUSION: Only ACRp90 responders showed a significant decrease in synovitis and the halting of structural damage, suggesting that levels of response higher than ACRp30 are more appropriate for assessing drug efficacy. The excellent responsiveness of MRI and its ability to detect subclinical synovitis make it a promising outcome measure.
24877754 The molecular mechanism of curcumol on inducing cell growth arrest and apoptosis in Jurkat 2014 Aug CD4(+) T cells in rheumatoid arthritis (RA) express growth signaling pathway in association with deregulated growth and resistance to apoptosis. The janus kinase (Jak) 3 and signal transducer and activator of transcription (STAT) pathway play a critical role in interleukin-2 (IL-2)-induced CD4(+) T cell proliferation. The present study aimed to explore the anti-cell proliferation mechanism of curcumol, a pure monomer extracted from Chinese medical plant Rhizoma curcumae. Cell proliferation was determined using WST-1 assay after curcumol treatment. The cell cycle distribution and Bcl-2 protein expression were assessed by flow cytometry. The cellular morphology of apoptosis was evaluated by Hoechst 33258 staining. The expressions of phosphorylated-Jak3 (p-Jak3), p-STAT3, and p-STAT5a following IL-2 stimulation were determined by western blot analysis. The Electrophoretic Mobility Shift Assay was used to detect the DNA binding activities of transcription factors STAT3 and STAT5. The study results showed that curcumol could inhibit the IL-2-induced Jurkat cell proliferation in a concentration- and time-dependent manner in vitro. Curcumol could cause cell cycle arrest at the S phase, induce cell apoptosis, and inhibit the expression of Bcl-2 in a dose-dependent manner. Curcumol at 50μg/mL and Jak3 inhibitor ZM39923 could inhibit the phosphorylation of Jak3 and STAT5a. In conclusion, the underlying mechanism of curcumol on suppressing CD4(+) T cell proliferation and inducing apoptosis might partly be mediated by inhibition of Jak3-STAT5-related molecular activities and Bcl-2 expression, respectively; further studies are required in vivo to test the use of curcumol as a promising therapeutic option for RA.
25306263 An investigation into the interactions of gold nanoparticles and anti-arthritic drugs with 2015 Jan Gold(I) complexes are an important tool in the arsenal of established approaches for treating rheumatoid arthritis (RA), while some recent studies have suggested that gold nanoparticles (Au NPs) may also be therapeutically efficacious. These observations prompted the current biological studies involving gold(I) anti-RA agents and Au NPs, which are aimed towards improving our knowledge of how they work. The cytotoxicity of auranofin, aurothiomalate, aurothiosulfate and Au NPs towards RAW264.7 macrophages was evaluated using the MTT assay, with the former compound proving to be the most toxic. The extent of cellular uptake of the various gold agents was determined using graphite furnace atomic absorption spectrometry, while their distribution within macrophages was examined using microprobe synchrotron radiation X-ray fluorescence spectroscopy. The latter technique showed accumulation of gold in discrete regions of the cell, and co-localisation with sulfur in the case of cells treated with aurothiomalate or auranofin. Electrospray ionization mass spectrometry was used to characterize thioredoxin reductase (TrxR) in which the penultimate selenocysteine residue was replaced by cysteine. Mass spectra of solutions of TrxR and aurothiomalate, aurothiosulfate or auranofin showed complexes containing bare gold atoms bound to the protein, or protein adducts containing gold atoms retaining some of their initial ligands. These results support TrxR being an important target of gold(I) drugs used to treat RA, while the finding that Au NPs are incorporated into macrophages, but elicit little toxicity, indicates further exploration of their potential for treatment of RA is warranted.
25121046 Genetic polymorphism of interleukin-18 gene promoter region in rheumatoid arthritis patien 2014 Jun BACKGROUND: Interleukin-18 (IL-18) is a pro inflammatory cytokine which plays a key role in the acute and chronic inflammatory phases of Rheumatoid Arthritis (RA). The Single Nucleotide Polymorphisms (SNPs) of IL-18 gene promoter region at positions -137 and -607, are postulated to be associated with RA. To test this, this study aimed to identify the association between these SNPs of the IL-18 gene promoter region of RA in south Indian patients. MATERIALS AND METHODS: This study was carried on 190 subjects among which 90 were RA patients and 100 were age and sex matched controls. Genomic DNA was extracted by Salting out method. IL 18 gene promotor region SNPs, IL 18 - 607 and IL 18 -137 were amplified by using sequence specific primers. The amplified products of different samples were separated by using a 1.5% agarose gel, stained with ethidium bromide and photographed. All statistical analyses were carried out by using SYSTAT 12 software. RESULTS: At position 607, the frequencies of C allele, CC genotype, A allele and AA genotype were found to be significantly higher in patients and controls respectively and there was no significant difference in CA genotype. At position 137, there was no significant difference between the two groups with regard to G and C allelles but there was a significant increase in GG genotype of patients and CC genotype of controls. There was no association between duration of morning stiffness, rheumatoid factor positivity or negativity, age of onset and gender with distribution of genotypes and alleles. CONCLUSION: C allele, CC genotype at position-607 and GG genotype at position-137 are risk factors and A allele, AA genotype at position-607 and CC genotype at position-137 have protective effect for RA.