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ID PMID Title PublicationDate abstract
23051717 Polymyalgia rheumatica. 2013 Jan 5 Polymyalgia rheumatica is a chronic, inflammatory disorder of unknown cause that affects people over age 50 years. Classic symptoms include pain and long-term morning stiffness of the neck, shoulders, hips, upper arms, and thighs. Although markers of inflammation are often raised, no specific laboratory test exists for the disorder and the diagnosis is based on clinical assessment. Provisional classification criteria were published in April, 2012, by a collaborative initiative of the European League Against Rheumatism and the American College of Rheumatology. Several other disorders can mimic polymyalgia rheumatica. In particular, clinical manifestations can be difficult to differentiate from other forms of inflammatory arthritis such as spondyloarthritis and rheumatoid arthritis. Imaging studies such as ultrasonography and MRI typically show a predominantly periarticular inflammatory process. A subset of patients has an associated inflammatory vasculopathy affecting large arteries (giant cell arteritis). The standard treatment is low-dose glucocorticoids, which provide symptomatic relief for most patients. However, disease relapses are common, and treatment with glucocorticoids is associated with substantial morbidity. Improved understanding of disease pathogenesis might allow for more targeted immunotherapy.
24534055 Primary headaches in pediatric patients with chronic rheumatic disease. 2014 Nov OBJECTIVES: To assess the presence, prevalence and clinical characteristics of primary headaches in pediatric patients with chronic rheumatic diseases such as juvenile idiopathic arthritis (JIA) and familial Mediterranean fever (FMF), and to analyze the common pathophysiological mechanisms. STUDY DESIGN: In this noncontrolled, cross-sectional study, a semi-structured 53 item headache questionnaire was administered to subjects with FMF and JIA, and interviewed a total sample size of 601 patients younger than16years of age. The questionnaires were then analyzed according to the International Headache Society's diagnostic criteria. RESULTS: Children with FMF (n=378) and JIA (n=223) were studied. Each group was then divided into two subgroups according to whether the subjects reported headache or not. 29.5% of subjects with FMF reported having migraine, 37.6% probable migraine and 32.9% tension type headache (TTH). In JIA group 28.2% were diagnosed with migraine; 41.2% with probable migraine and 30.6% with TTH. No significant difference was found between all subjects with (n=258) and without (n=343) headache for variables such as living in a crowded family (p=0.95), being the first child in the family (p=0.63), academic achievement of the child (p=0.63), high education level (higher than high school) of the mother (p=0.52) and father (p=0.46). The presence of systemic disease was reported not to be effecting the daily life at the time of evaluation by 90.2% of the children with headache and 91.0% of the children without headache (p=0.94). 81.4% of the children reported their headaches were not aggravating with the exacerbation periods of their systemic disease. Family history of hypertension was reported higher by the subjects with headache (13.5% with headache and 4.0% without headache p=0.001). Diabetes mellitus was also reported higher (5.8% with headache; 0.5% without headache; p=0.006). Family history of headache was reported in 28.2% of the patients with headache whereas it was 17.4% of the patients without headache (p<0.001). Family history of headache was reported in 28.2% of the FMF subjects with headache whereas it was 17.4% of the patients without headache (p<0.001). For JIA patients a positive family history for headache was obtained in 25.9% of children with headache notably in migraineurs (81.8%). CONCLUSION: Patients with JIA and FMF should be asked specifically about accompanying primary headaches particularly migraine headaches as they may be additional disabilities for these patients.
24561351 Metabonomic study of Wu-tou decoction in adjuvant-induced arthritis rat using ultra-perfor 2014 Mar 15 A urinary metabonomics method based on the ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) had been established to investigate the holistic efficacy of Wu-tou decoction (WTD), a traditional Chinese medicine (TCM) formula used to treat rheumatoid arthritis (RA), in adjuvant-induced arthritis (AIA) rat model. Multivariate statistical approaches, such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were used to distinguish healthy control group, AIA model group and WTD treated group and find potential biomarkers. There was a clear separation among the three groups in PCA model. Sixteen potential biomarkers had been identified using OPLS-DA, and 11 of them was considered to be in response to therapeutic effects of WTD involved in tryptophan metabolism, phenylalanine metabolism, tricarboxylic acid (TCA) cycle, bile acid biosynthesis, steroid hormone biosynthesis and valine metabolism. In this study, WTD also showed good anti-inflammatory and antioxidant activities in vivo, and it could suppress histopathological changes of AIA rats. There might be a correlation between these results and the regulation of the disturbed metabolites in urine. This study demonstrates that metabonomics is a powerful methodology to gain insight in the mechanism of TCM formula in therapy.
24444779 Attenuation of the progression of adjuvant-induced arthritis by 3-aminobenzamide treatment 2014 Mar Rheumatoid arthritis (RA) is a disease that is still insufficiently controlled by current treatments. Poly(ADP-ribose) polymerase (PARP) inhibitors ameliorate immune-mediated diseases in several experimental models, including RA, colitis, experimental autoimmune encephalomyelitis and allergy. Together these findings showed that ADP-ribosylating enzymes, in particular PARP-1, play a pivotal role in the regulation of immune responses and may represent a noble target for new therapeutic approaches in immune-mediated diseases. The effect of 3-aminobenzamide (3-AB), an inhibitor of poly(ADP-ribose) synthetase activity, was evaluated in a mouse model of adjuvant-induced arthritis (AIA) on pro-inflammatory cytokines, adhesion molecules, inflammatory mediators and chemokine production/expression in serum and knee joint. Histopathological examination was also done on joint section. Our data demonstrates that 3-AB, 10mg/kg, intraperitoneally (i.p.) significantly reduces pro-inflammatory cytokine (IL-17, TNF-α and IL-2) and chemokine (MCP-1 and MIP-2) production/expression, accompanied by amelioration of the disease as indicated by reduced paw swelling and arthritic scores and was associated with a significant reduction of VCAM-1 and ICAM-1 expression in the knee joint. Moreover, the expression of inflammatory mediators (iNOS, COX-2, MMP-2, MMP-9) and joint histological inflammatory damage was also markedly decreased. The results of this study suggest that PARP-1 inhibitor may play a role in the inflammatory arthritic process after administration of 3-AB may be a beneficial therapeutic approach.
23400582 Adoptive transfer of human gingiva-derived mesenchymal stem cells ameliorates collagen-ind 2013 May OBJECTIVE: Current approaches offer no cures for rheumatoid arthritis (RA). Accumulating evidence has revealed that manipulation of bone marrow-derived mesenchymal stem cells (BM-MSCs) may have the potential to control or even prevent RA, but BM-MSC-based therapy faces many challenges, such as limited cell availability and reduced clinical feasibility. This study in mice with established collagen-induced arthritis (CIA) was undertaken to determine whether substitution of human gingiva-derived mesenchymal stem cells (G-MSCs) would significantly improve the therapeutic effects. METHODS: CIA was induced in DBA/1J mice by immunization with type II collagen and Freund's complete adjuvant. G-MSCs were injected intravenously into the mice on day 14 after immunization. In some experiments, intraperitoneal injection of PC61 (anti-CD25 antibody) was used to deplete Treg cells in arthritic mice. RESULTS: Infusion of G-MSCs in DBA/1J mice with CIA significantly reduced the severity of arthritis, decreased the histopathology scores, and down-regulated the production of inflammatory cytokines (interferon-γ and interleukin-17A). Infusion of G-MSCs also resulted in increased levels of CD4+CD39+FoxP3+ cells in arthritic mice. These increases were noted early after infusion in the spleens and lymph nodes, and later after infusion in the synovial fluid. The FoxP3+ Treg cells that were increased in frequency mainly consisted of Helios-negative cells. When Treg cells were depleted, infusion of G-MSCs partially interfered with the progression of CIA. Pretreatment of G-MSCs with a CD39 or CD73 inhibitor significantly reversed the protective effect of G-MSCs on CIA. CONCLUSION: The role of G-MSCs in controlling the development and severity of CIA mostly depends on CD39/CD73 signals and partially depends on the induction of CD4+CD39+FoxP3+ Treg cells. G-MSCs provide a promising approach for the treatment of autoimmune diseases.
25181348 Glucose kinetics in the collagen-induced arthritis model: an all-in-one model to assess bo 2014 Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory drugs, but chronic use is hampered by metabolic side effects. Therefore, there is an urgent medical need for improved GCs that are as effective as classical GCs but have a better safety profile. A well-established model to assess anti-inflammatory efficacy is the chronic collagen-induced arthritis (CIA) model in mice, a model with features resembling rheumatoid arthritis. Models to quantify undesired effects of glucocorticoids on glucose kinetics are less well-established. Recently, we have described a model to quantify basal blood glucose kinetics using stably-labeled glucose. In the present study, we have integrated this blood glucose kinetic model in the CIA model to enable quantification of both efficacy and adverse effects in one animal model. Arthritis scores were decreased after treatment with prednisolone, confirming the anti-inflammatory properties of GCs. Both inflammation and prednisolone induced insulin resistance as insulin secretion was strongly increased whereas blood glucose concentrations and hepatic glucose production were only slightly decreased. This insulin resistance did not directly resulted in hyperglycemia, indicating a highly adaptive compensatory mechanism in these mice. In conclusion, this 'all-in-one' model allows for studying effects of (novel) GC compounds on the development of arthritis and glucose kinetics in a single animal. This integrative model provides a valuable tool for investigating (drug-induced) metabolic dysregulation in an inflammatory setting.
25336631 Transglutaminase factor XIII promotes arthritis through mechanisms linked to inflammation 2015 Jan 15 Rheumatoid arthritis is a chronic inflammatory disease characterized by synovial hyperplasia, inflammatory cell infiltration, irreversible cartilage and bone destruction, and exuberant coagulation system activity within joint tissue. Here, we demonstrate that the coagulation transglutaminase, factor XIII (fXIII), drives arthritis pathogenesis by promoting local inflammatory and tissue degradative and remodeling events. All pathological features of collagen-induced arthritis (CIA) were significantly reduced in fXIII-deficient mice. However, the most striking difference in outcome was the preservation of cartilage and bone in fXIIIA(-/-) mice concurrent with reduced osteoclast numbers and activity. The local expression of osteoclast effectors receptor activator of nuclear factor-κB ligand (RANKL) and tartrate resistant acid phosphatase were significantly diminished in CIA-challenged and even unchallenged fXIIIA(-/-) mice relative to wild-type animals, but were similar in wild-type and fibrinogen-deficient mice. Impaired osteoclast formation in fXIIIA(-/-) mice was not due to an inherent deficiency of monocyte precursors, but it was linked to reduced RANKL-driven osteoclast formation. Furthermore, treatment of mice with the pan-transglutaminase inhibitor cystamine resulted in significantly diminished CIA pathology and local markers of osteoclastogenesis. Thus, eliminating fXIIIA limits inflammatory arthritis and protects from cartilage and bone destruction in part through mechanisms linked to reduced RANKL-mediated osteoclastogenesis. In summary, therapeutic strategies targeting fXIII activity may prove beneficial in limiting arthropathies and other degenerative bone diseases.
24000795 Genomic characterization of remission in juvenile idiopathic arthritis. 2013 Aug 30 INTRODUCTION: The attainment of remission has become an important end point for clinical trials in juvenile idiopathic arthritis (JIA), although we do not yet have a full understanding of what remission is at the cell and molecular level. METHODS: Two independent cohorts of patients with JIA and healthy child controls were studied. RNA was prepared separately from peripheral blood mononuclear cells (PBMC) and granulocytes to identify differentially expressed genes using whole genome microarrays. Expression profiling results for selected genes were confirmed by quantitative, real-time polymerase chain reaction (RT-PCR). RESULTS: We found that remission in JIA induced by either methotrexate (MTX) or MTX plus a TNF inhibitor (etanercept, Et) (MTX + Et) is characterized by numerous differences in gene expression in peripheral blood mononuclear cells and in granulocytes compared with healthy control children; that is, remission is not a restoration of immunologic normalcy. Network analysis of the differentially expressed genes demonstrated that the steroid hormone receptor superfamily member hepatocyte nuclear factor 4 alpha (HNF4α) is a hub in several of the gene networks that distinguished children with arthritis from controls. Confocal microscopy revealed that HNF4a is present in both T lymphocytes and granulocytes, suggesting a previously unsuspected role for this transcription factor in regulating leukocyte function and therapeutic response in JIA. CONCLUSIONS: These findings provide a framework from which to understand therapeutic response in JIA and, furthermore, may be used to develop strategies to increase the frequency with which remission is achieved in adult forms of rheumatoid arthritis.
23749611 Treating spondyloarthritis, including ankylosing spondylitis and psoriatic arthritis, to t 2014 Jan BACKGROUND: Therapeutic targets have been defined for diseases like diabetes, hypertension or rheumatoid arthritis and adhering to them has improved outcomes. Such targets are just emerging for spondyloarthritis (SpA). OBJECTIVE: To define the treatment target for SpA including ankylosing spondylitis and psoriatic arthritis (PsA) and develop recommendations for achieving the target, including a treat-to-target management strategy. METHODS: Based on results of a systematic literature review and expert opinion, a task force of expert physicians and patients developed recommendations which were broadly discussed and voted upon in a Delphi-like process. Level of evidence, grade and strength of the recommendations were derived by respective means. The commonalities between axial SpA, peripheral SpA and PsA were discussed in detail. RESULTS: Although the literature review did not reveal trials comparing a treat-to-target approach with another or no strategy, it provided indirect evidence regarding an optimised approach to therapy that facilitated the development of recommendations. The group agreed on 5 overarching principles and 11 recommendations; 9 of these recommendations related commonly to the whole spectrum of SpA and PsA, and only 2 were designed separately for axial SpA, peripheral SpA and PsA. The main treatment target, which should be based on a shared decision with the patient, was defined as remission, with the alternative target of low disease activity. Follow-up examinations at regular intervals that depend on the patient's status should safeguard the evolution of disease activity towards the targeted goal. Additional recommendations relate to extra-articular and extramusculoskeletal aspects and other important factors, such as comorbidity. While the level of evidence was generally quite low, the mean strength of recommendation was 9-10 (10: maximum agreement) for all recommendations. A research agenda was formulated. CONCLUSIONS: The task force defined the treatment target as remission or, alternatively, low disease activity, being aware that the evidence base is not strong and needs to be expanded by future research. These recommendations can inform the various stakeholders about expert opinion that aims for reaching optimal outcomes of SpA.
23873820 Biologic treatment response among adults with juvenile idiopathic arthritis: results from 2013 Oct OBJECTIVE: To describe the use of and response to biologic therapies commenced in adults with JIA. METHODS: Patients with arthritis onset <16 years were identified from the British Society for Rheumatology Biologics Register for rheumatoid arthritis (BSRBR-RA) and stratified into ILAR JIA subtypes. Patterns of biologic use and treatment persistence were explored, with disability levels (HAQ) and remission rates [28-Joint Disease Activity Score (DAS28)] evaluated at 6 and 12 months. RESULTS: Arthritis with an onset of <16 years was confirmed in 225 patients and the ILAR subtype was determined in 154 (68%). Only 58 (26%) patients had a diagnosis of JIA recorded in the BSRBR-RA. The median age at biologic commencement was 31 years [interquartile range (IQR) 23-39] and 76% were female. The biologic therapies were etanercept (49%), infliximab (28%), adalimumab (22%) and anakinra (1%). Fifty per cent of patients received more than one biologic during follow-up (2 agents, n = 64; ≥3 agents, n = 49). Treatment persistence at 1 year was 78% (95% CI 71%, 82%), falling to 42% (95% CI 34%, 49%) at 5 years. Both the HAQ and DAS28 improved significantly at 6 months, with 21% and 28% of patients in remission (DAS28 < 2.6) at 6 and 12 months, respectively. CONCLUSION: This study describes patterns and identifies outcomes of biologic use in a national cohort of adults with JIA. With no national guidance currently available in this area, the choice of first biologic was inconsistent, although treatment outcomes were good. These data confirm that biologic therapies are an important treatment option in adults with active JIA in adulthood.
23108632 Contribution of salivary gland ultrasonography to the diagnosis of Sjögren's syndrome: to 2013 Jan OBJECTIVE: To determine the accuracy of salivary gland ultrasonography (SGUS) for diagnosing primary Sjögren's syndrome (SS) and to suggest modifications of the American-European Consensus Group (AECG) classification criteria. METHODS: We conducted a cross-sectional study in a prospective cohort of patients with suspected primary SS that was established between 2006 and 2011. The echostructure of the bilateral parotid and submandibular glands was graded from 0 to 4, and the gland size was measured; blood flow to the parotid gland was assessed using Doppler waveform analysis. The reference standard was a clinical diagnosis of primary SS as determined by a group of experts blinded to the results of SGUS. Receiver operating characteristic (ROC) curve analysis was performed to compare the diagnostic value of the 0-4-point echostructure grade for each of the 4 major salivary glands, the sum of the grades for the 4 glands, and the highest grade among the 4 glands. RESULTS: Of the 158 patients in the study, 78 had a diagnosis of primary SS according to the experts, including 61 patients (78.2%) who met the AECG criteria. Doppler waveform analysis and gland size measurement showed poor diagnostic performance. The results of ROC curve analysis showed that the highest grade among the 4 glands provided the best diagnostic value. The optimal grade cutoff was 2 (62.8% sensitivity and 95.0% specificity). A weighted score was constructed using scores for the 5 variables selected by logistic regression analysis, as follows: (salivary flow×1.5)+(Schirmer's test×1.5)+(salivary gland biopsy×3)+(SSA/SSB×4.5)+(SGUS×2). According to ROC curve analysis, a score of ≥5 of 12.5 had 85.7% sensitivity and 94.9% specificity, compared with 77.9% sensitivity and 98.7% specificity for the AECG criteria. The addition of SGUS to the AECG criteria increased sensitivity to 87.0% but did not change specificity. CONCLUSION: Modifications of the AECG criteria, including the addition of a SGUS score, notably improved diagnostic performance.
21120495 Nephrocalcinosis and hypokalemia in a patient with primary Sjögren's syndrome. 2013 Mar Clinically significant renal involvement is uncommon in primary Sjögren's syndrome, amid which tubulointerstitial disorders, distal renal tubular acidosis (dRTA) particularly, account for the majority. Conversely, Sjögren's syndrome comprises at least half the patients presenting with renal tubular acidosis. While underlying dRTA itself is an important cause of nephrocalcinosis and urolithiasis, nephrocalcinosis is rarely a presenting feature of primary Sjögren's syndrome. I report a 41-year-old female contracting nephrocalcinosis and hypokalemia as complications of primary Sjögren's syndrome with dRTA, hereby to emphasize the importance of alkali therapy.
23838523 Lip biopsy for the diagnosis of Sjögren's syndrome: beware of the punch. 2014 Jan A pilot study was performed to examine the presence of nerve fibres in minor salivary gland tissue samples obtained by two procedures: punch and linear incisional techniques. The study was undertaken on a convenience sample of five cryopreserved corpses (mean age 74 ± 3.5 years; three males and two females). Biopsies were performed on the buccal side of the lower lip, between the mid-line and the corner of the mouth. Each corpse had one side of the lower lip biopsied by punch and the contralateral side using a linear incision. All punch samples (100%) displayed severed nerve fibres, whereas no nerve fibres (0%) could be identified in the samples obtained by means of the linear incision technique. While the linear incision approach permitted retrieval of at least five glands, punch biopsies did not provide enough material for the diagnosis of Sjögren's syndrome. Within the limitations of the study, our results strongly discourage the punch technique for minor salivary gland lip biopsy and provide information on the superiority of the linear incisional biopsy in terms of neural damage. These results may also promote the undertaking of clinical trials on patients in whom Sjögren's syndrome is suspected, comparing the morbidity associated with the linear incisional technique vs. minimally invasive biopsies.
24880453 The role of a labial salivary gland biopsy in the diagnostic procedure for Sjögren's synd 2014 Jul 1 OBJECTIVES: The purpose of the present study is to examine the role of the outcome of the labial salivary gland biopsy (LSGB) in the diagnostic procedure of patients suspected of suffering from Sjögren's syndrome (SS). MATERIAL AND METHODS: In a retrospective study the result of histopathological assessment of 94 consecutively taken labial salivary gland biopsies has been examined. For the diagnosis of SS the American-European Consensus Group classification (AECG, 2002) have been used. The outcome of the assessment has been discussed in relation to a recently reported classification provided by the American College of Rheumatology (ACR, 2012). RESULTS: In the 94 LSGBs support for a diagnosis of SS has been encountered in 24 out of 26 patients with SS. In the 68 patients with a negative diagnosis of SS only six positive LSGBs were observed. The sensitivity of the labial biopsy amounted 0.92; the specificity was 0.91, while the positive predictive value and the negative predictive value amounted 0.80 and 0.97 respectively. LSGBs taken by or on the request of the departments of Rheumatology or Internal Medicine had a significant higher yield compared to LSGBs taken in other clinical departments. CONCLUSIONS: The LSGB may play a role in the diagnostic procedure of Sjögren's syndrome when using either the AECG classification or the ACR classification. A LSGB should preferably taken after counseling for the possible presence of SS by a department of Rheumatology or Internal Medicine since the yield of such biopsies is much higher than in patients who have not been counseled by these departments prior to the taking of a LSGB. When using the ACR classification, a positive serologic result and a positive ocular test make the taking of a LSGB redundant. Only in case of a negative serologic outcome or a negative result of the ocular test a LSGB is indicated. Since both the serologic test and the ocular test carry hardly any morbidity, these tests should, indeed, be performed first before considering to take a LSGB.
24786923 Comparison of labial minor salivary gland biopsies from childhood Sjögren syndrome and ag 2014 Jun OBJECTIVE: To determine an appropriate focus score cutoff for childhood Sjögren syndrome (SS). METHODS: Labial salivary gland tissue from specimens from children with SS and age-matched controls was retrospectively identified and reviewed by a blinded oral pathologist. RESULTS: The presence of any focal sialadenitis (focus score > 0 foci/4 mm(2)) was common among childhood SS samples but present in only 1 of 8 control samples. CONCLUSION: The presence of any focal lymphocytic sialadenitis in minor labial salivary gland tissue is suggestive of childhood SS and should be included in future childhood SS-specific diagnostic or classification criteria.
24316710 Clinical and laboratorial profile and histological features on minor salivary glands from 2014 May 1 Diagnosis of Sjögren's syndrome (SS) is complex and the usefulness of labial minor salivary glands biopsy in this process remains controversial. OBJECTIVE: to evaluate the clinical and laboratorial profile and histological features on labial minor salivary glands from patients under investigation of SS. STUDY DESIGN: clinical charts from 38 patients under suspicion of SS and submitted to labial minor salivary glands biopsies were reviewed. Clinical and laboratorial data were retrieved from the clinical files and the HE-stained histological slides were reviewed under light microscopy. RESULTS: mean age of the patients was 56.5 years and 97% were females; histological analysis showed that 42% of the cases showed ductal dilatation, lymphocytic foci were found in 52.6% and, from this group, 80% of the cases presented a foci/lobules ratio above 0.8. Acinar/ductal ratio was considered diminished in 39.5% of the samples. Thirty six (95%) and 32 (84%) patients, respectively, complained about xerostomia and xerophthalmia. A study of the time interval of the symptoms that led to SS investigation showed a mean of 116 months. Moreover, sixty-six percent of the patients had already been submitted to immunosuppressive therapy prior to the labial minor salivary gland biopsy. Age of the patients, scintigraphic alterations on salivary function, antinuclear factor (ANF), anti-Ro and anti-La did not show statistical significant association with the histological features. Lobules/foci ratio above 0.8 was the only histological parameter statistically associated with Sjögren's syndrome diagnosis (p<0.0001). CONCLUSIONS: in the studied sample, lymphocytic foci on salivary glands were the only histological parameter associated to the diagnosis of SS. Early indication of labial minor salivary gland biopsy to patients under investigation of SS could limit the effects of immunosuppressive therapy on the histological features associated with the evolution of salivary gland involvement in SS.
25308129 Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by 2014 Dec Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting the synovial joints. The currently available drugs for RA are effective only in a proportion of patients and their prolonged use is associated with severe adverse effects. Thus, new anti-arthritic agents are being sought. We tested Pristimerin, a naturally occurring triterpenoid, for its therapeutic activity against rat adjuvant arthritis. Pristimerin effectively inhibited both arthritic inflammation and cartilage and bone damage in the joints. Pristimerin-treated rats exhibited a reduction in the pro-inflammatory cytokines (IL-6, IL-17, IL-18, and IL-23) and the IL-6/IL-17-associated transcription factors (pSTAT3 and ROR-γt), coupled with an increase in the immunomodulatory cytokine IL-10. Also increased was IFN-γ, which can inhibit IL-17 response. In addition, the Th17/Treg ratio was altered in favor of immune suppression and the RANKL/OPG ratio was skewed towards anti-osteoclastogenesis. This is the first report on testing Pristimerin in arthritis. We suggest further evaluation of Pristimerin in RA patients.
22798567 The development of candidate composite disease activity and responder indices for psoriati 2013 Jun OBJECTIVE: To develop new composite disease activity indices for psoriatic arthritis (PsA). METHODS: Data from routine clinic visits at multiple centres were collected in a systematic manner. Data included all domains identified as important in randomised controlled trials in PsA. Decisions to change treatment were used as surrogates for high disease activity. New indices were developed by multiple linear regression (psoriatic arthritis disease activity score: PASDAS) and empirically, utilising physician-defined cut-offs for disease activity (arithmetic mean of desirability functions: AMDF). These were compared with existing composite measures: Composite Psoriatic arthritis Disease Activity Index (CPDAI), Disease Activity for PSoriatic Arthritis (DAPSA), and Disease Activity Score for rheumatoid arthritis (DAS28). RESULTS: 161/503 (32%) subjects had treatment changes. Although all measures performed well, compared with existing indices, PASDAS was better able to discriminate between high and low disease activity (area under receiver operating curves (ROC)) curve with 95% CI: PASDAS 0.773 (0.723, 0.822); AMDF 0.730 (0.680, 0.780); CPDAI 0.719 (0.668, 0.770); DAPSA 0.710 (0.654, 0.766); DAS28 0.736 (0.680, 0.792). All measures were able to discriminate between disease activity states in patients with oligoarthritis, although area under the receiver operating curves (AUC) were generally smaller. In patients with severe skin disease (psoriasis area and severity index>10) both nonparametric and AUC curve statistics were nonsignificant for all measures. CONCLUSIONS: Two new composite measures to assess disease activity in PsA have been developed. Further testing in other datasets, including comparison with existing measures, is required to validate these instruments.
24190602 Comparative study by computed radiography, histology, and scanning electron microscopy of 2014 Jan In the northeast of Brazil, caprine arthritis-encephalitis (CAE) is one of the key reasons for herd productivity decreasing that result in considerable economic losses. A comparative study was carried out using computed radiography (CR), histological analysis (HA), and scanning electronic microscopy (SEM) of the joints of CAE infected and normal goats. Humerus head surface of positive animals presented reduced joint space, increased bone density, and signs of degenerative joint disease (DJD). The carpal joint presented no morphological alterations in CR in any of the animals studied. Tarsus joint was the most affected, characterized by severe DJD, absence of joint space, increased periarticular soft tissue density, edema, and bone sclerosis. Histological analysis showed chronic tissue lesions, complete loss of the surface zone, absence of proteoglycans in the transition and radial zones and destruction of the cartilage surface in the CAE positive animals. Analysis by SEM showed ulcerated lesions with irregular and folded patterns on the joint surface that distinguished the limits between areas of normal and affected cartilage. The morphological study of the joints of normal and CAE positive goats deepened understanding of the alteration in the tissue bioarchitecture of the most affected joints. The SEM finding sustained previous histological reports, similar to those found for rheumatoid arthritis, suggesting that the goat infected with CAE can be considered as a potential model for research in this area.
22887862 Autoantibodies against galectins are associated with antiphospholipid syndrome in patients 2013 Jan The presence of autoantibodies against immunoregulatory effectors can be relevant for onset and/or the progression of autoimmune disease. Emerging insights into an immunological activity profile including a role as opsonins give reason to systematically monitor sera of patients for immunoglobulin G (IgG) autoantibodies, preferably for several galectins at the same time. Here, we report on a study of chronic inflammatory rheumatic diseases, i.e. systemic lupus erythematosus (SLE; pilot cohort p, n = 40; confirmation cohort c, n = 109), rheumatoid arthritis (RA; p, n = 32; c, n = 25) and primary antiphospholipid syndrome (APS; c, n = 64). Enzyme-linked immunosorbent assay-based series using galectin-1, -2, -3, -4, -7, -8 and -9 and natural processing products, i.e. the truncated version of galectin-3 and the N-terminal domains of galectin-4, -8 and -9, were performed. Normal healthy donors (p, n = 20; c, n = 21) and patients with paraproteins (c, n = 19) served as controls. Highly significant optical density-value readings for IgG autoantibodies were consistently detected for the proto-type galectin-7 (SLE) and the tandem repeat-type galectin-8 and -9 (SLE and RA). Their presence was independent from the autoantibody status against double-stranded DNA (for patients with SLE) or a rheumatoid factor (for patients with RA), respectively. Importantly, anti-galectin-2 autoantibodies highly significantly correlated with the appearance of a secondary APS in patients with SLE so that this parameter may serve as an additional biomarker for APS. Equally of note, the presence of IgG autoantibodies against galectins capable to act as an opsonin may contribute to a sustained immune dysregulation in patients with chronic inflammatory rheumatic diseases.