Prognosis Of Rheumatoid Arthritis Patients Research Articles

Efficacy of PF-06651600 in alleviating the pro-inflammatory capacity of CD4+ T cells in rheumatoid arthritis patients.

PF-06651600 is a highly specific inhibitor of Janus-activated kinase 3 and the Tec family of kinases. Regarding its dual function in the inhibition of both γc cytokine receptors and T cell receptor signaling, the present study aimed at evaluating the impact of PF-06651600 on the status of T-helper cells (Th) as the central game players in the pathogenesis of rheumatoid arthritis (RA). TCD4+ cells were isolated from 34 RA patients and 15 healthy control individuals and were evaluated after treatment with PF-06651600. RA patients had higher percentages of TCD4+ cells, CD4+ PD-1+ cells, and CD4+ PD-1+ TIGIT+ cells compared to a healthy control group and the TCD4+ cells of these patients showed higher interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and interleukin (IL)-17 secretion along with higher messenger RNA (mRNA) expressions of T-bet. The percentage of CD4+ PD-1+ TIGIT+ cells showed a reverse correlation with the Disease Activity Score of 28 joints of the RA patients. PF-06651600 caused a significant decrease in the mRNA expressions of T-bet and RAR-related orphan receptor γt and the secretion of interferon (IFN)-γ and TNF-α in TCD4+ cells of RA patients. On the other hand, the population of CD4+ PD-1+ TIGIT+ cells was expanded under the influence of PF-06651600. This treatment also reduced the proliferation of TCD4+ cells. PF-06651600 demonstrated a potential to modulate the activity of TCD4+ cells in RA patients and to reduce the commitment of Th cells to the pathogenic Th1 and Th17 subsets. Further, it caused TCD4+ cells to gain an exhausted phenotype which is associated with better prognosis in RA patients.

Gastrointestinal Conditions in Rheumatoid Arthritis Patients

Rheumatoid arthritis (RA) is a serious medical and social problem, characterised by a steadily progressive disorganisation of the connective tissue, based on profound immunopathological changes with autoaggressive features. RA ranks first in terms of prevalence among inflammatory diseases of the joints. The social significance of this disease is determined not only by its high prevalence, but also by the great material damage caused to society, the patient and his family due to the high incapacity and early onset of disability. Steady progression of the pathological process despite the use of modern therapeutic methods results not only in significant functional insufficiency of the locomotor apparatus but also in the shortening of the patients' life span by 4-10 years and the increase of the death rate which exceeds that of the general population. The prognosis of RA patients with systemic manifestations is particularly unfavorable: generalized vasculitis, rheumatoid nodules, lymphoadenopathy, lung, heart, liver, kidney and other organs and systems are affected. Among the extra-articular manifestations of RA, gastrointestinal (GI) lesions are the least studied, although the most severe process, intestinal amyloidosis, is well known, occurring in 11% of patients and usually combined with amyloidosis of other internal organs.

Impact of disease duration on proteomic bioprofile and prognosis in rheumatoid arthritis patients.

Cardiovascular disease worsens the prognosis of rheumatoid arthritis (RA) and vice-versa. Inflammation may be a common pathway for both conditions. It is expected that a longer RA duration leads to a greater inflammatory cumulative exposure burden; however, studies on the association between RA disease duration and outcomes are scarce. Our aim is to compare the characteristics, biomarker expression and outcomes according to the duration of RA. Prospective cohort study including 399 RA patients, with detailed clinical, echocardiographic, and proteomic phenotyping that were compared across tertiles of RA disease duration. Cox proportional models were used to study the association of disease duration with cardiovascular outcomes. RA duration tertiles were: tertile 1 with median of 3.2; tertile 2 with median of 8.8; and tertile 3 with median of 21.8 years. Compared to tertile 1, patients in tertile 3 were older, had more erosive disease, more frequent echocardiographic alterations, lower haemoglobin and walked a shorter distance on the 6MWT. Natriuretic peptides, cathepsin L1, galectin 9, matrix metalloproteinase-12, adrenomedullin and tumour necrosis factor receptor 11A were higher in patients with longer disease duration. Compared to patients in tertile 1, those in tertile 3 had higher risk of a subsequent cardiovascular hospitalisation or cardiovascular death (HR 2.71, 95%CI 1.06-6.92, p=0.04). RA patients with longer disease duration had more organ damage and worse outcomes than those with shorter disease duration. Biomarker expression suggested that patients with longer RA duration had activation of pathways related to inflammation, extracellular matrix organisation, fibrosis and congestion.

Clinical utility of anti-carbamylated antibody in rheumatoid arthritis female patients: Emerging predictive value compared to anti-cyclic citrullinated peptide and rheumatoid factor

Aim of the workTo evaluate the frequency of anti-carbamylated protein (anti-CarP) antibodies positivity in female rheumatoid arthritis (RA) patients; to study their association with different disease aspects clinically and radiologically and to assess their potential predictive role of RA disease compared to other autoantibodies. Patients and methodsFifty-one RA female patients and 44 age-matched controls were studied. Duration of morning stiffness, disease activity score (DAS28) and health assessment questionnaire (HAQ) were assessed. Laboratory investigations included acute phase reactants, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies. Conventional radiography of both hands and feet was performed and assessed by a simple erosion narrowing score (SENS). All patients were evaluated by ultrasound 7 (US7) score. ResultsThe mean age of patients was 46.9 ± 8.6 years with disease duration of 6.2 ± 5.3 years. Anti-CarP antibody was positive in 52% and 54.5% of patients seronegative for anti-CCP and RF respectively. RF was positive in 40 (78.4), anti-CCP was positive in 26(51%), and anti-CarP in 21 (41.2%) patients. Anti-CarP antibodies were significantly associated with radiological damage, DAS28, HAQ and acute phase reactants. The sensitivity and specificity were 41.2% and 88.6%, respectively for anti-CarP, 51% and 93.2% for anti-CCP and 78.4% and 90.9% for RF to diagnose RA. ConclusionsAn association between anti-CarP antibody positivity and the disease activity, severity, structural damage and hence poor disease outcome has been demonstrated. Testing anti-CarP antibodies could be a useful marker for the assessment of disease activity as well as the expectation of prognosis in RA patients.

Prognostic factors for the short-term mortality of patients with rheumatoid arthritis admitted to intensive care units

BackgroundPatients with rheumatoid arthritis (RA) have high mortality risk and are frequently treated in intensive care units (ICUs).MethodsThis was a retrospective observational study. This study included 67 patients (20 males, 47 females) with RA who were admitted at the ICU of our institution for ≥48 h between January 2008 and December 2017. We analyzed the 30-day mortality of these patients and the investigated prognostic factors in RA patients admitted to our ICU.ResultsUpon admission, the median age was 70 (range, 33–96) years, and RA duration was 10 (range, 0–61) years. The 5-year survival after ICU admission was 47%, and 30-day, 90-day, and 1-year mortality rates were 22, 27, and 37%, respectively. The major reasons for ICU admission were cardiovascular complications (24%) and infection (40%) and the most common ICU treatments were mechanical ventilation (69%), renal replacement (25%), and vasopressor (78%). In the 30-day mortality group, infection led to a fatal outcome in most cases (67%), and nonsurvival was associated with a significantly higher glucocorticoid dose, updated Charlson’s comorbidity index (CCI), and acute physiology and chronic health evaluation (APACHE) II score. Laboratory data obtained at ICU admission showed that lower platelet number and total protein and higher creatinine and prothrombin time international normalized ratio (PT-INR) indicated significantly poorer prognosis. The multivariate Cox proportional hazard model revealed that nonuse of csDMARDs, high updated CCI, increased APACHE II score, and prolonged PT-INR were associated with a higher risk of mortality after ICU admission.ConclusionOur study demonstrated that the nonuse of csDMARDs, high updated CCI, elevated APACHE II score, and coagulation abnormalities predicted poorer prognosis in RA patients admitted to the ICU.

A Neutrophil Activation Biomarker Panel in Prognosis and Monitoring of Patients With Rheumatoid Arthritis.

Exaggerated neutrophil activation and formation of neutrophil extracellular traps (NETs) are linked to inflammation and autoimmunity, including rheumatoid arthritis (RA). However, whether NETs are present in the circulation of RA patients and contribute to inflammation and disease progression has not been carefully addressed. We undertook this study to assess markers of neutrophil activation and NET formation in plasma samples, investigating whether they add clinical value in improving the determination of prognosis and monitoring in RA patients. Markers of neutrophil activation (calprotectin) and cell death (NETs) were analyzed, using enzyme-linked immunosorbent assay, in serum and plasma obtained from patients in 3 cross-sectional RA cohorts and sex-matched healthy controls. A longitudinal inception cohort (n = 247), seen for a median follow-up of 8 years, was used for predictive analyses. Markers of neutrophil activation and cell death were increased in RA patients compared to healthy individuals (P < 0.0001). Calprotectin levels correlated with the Clinical Disease Activity Index (r = 0.53, P < 0.0001) and could be used to distinguish between patients with disease in remission and those with active disease, an observation not seen when examining C-reactive protein levels. A biomarker panel consisting of anti-citrullinated protein antibody and calprotectin could predict erosive disease (odds ratio [OR] 7.5, P < 0.0001) and joint space narrowing (OR 4.9, P = 0.001). NET levels were associated with markers of inflammation (P = 0.0002). Furthermore, NETs and a "neutrophil activation signature" biomarker panel had good predictive value in identifying patients who were developing extraarticular nodules (OR 5.6, P = 0.006). Neutrophils undergo marked activation and cell death in RA. Neutrophil biomarkers can provide added clinical value in the monitoring and prognosis of RA patients and may allow for early preventive treatment intervention.

Anti-RANKL antibody for the treatment of bone and cartilage destruction in rheumatoid arthritis

Rheumatoid arthritis (RA) is characterized by chronic synovitis and RANKL-dependent osteoclastogenesis leading to bone damage, which causes severe physical disability. Focal and systemic bone and cartilage destruction including secondary osteoporosis contributes to the morbidity associated with RA. The biologics targeting TNF and IL-6 has revolutionized the treatment of RA, producing significant improvements in clinical and structural outcomes. Furthermore, an anti-RANKL antibody denosumab possesses a potential to inhibit joint destruction as well as systemic osteoporosis. Targeting RANKL therapy will most likely enlarge the possibilities of osteoporosis treatment and improve the prognosis in RA patients.

EULAR RECOMMENDATIONS FOR THE TREATMENT OF RHEUMATOID ARTHRITIS – 2013: GENERAL CHARACTERISTICS AND DISPUTABLE PROBLEMS

Система комплексной поддержки и сопровождения научного журнала Elpub позволяет запустить двуязычный сайт журнала со встроенной системой электронной редакции в соответствии с лучшими издательскими практиками, а так же предусматривает техническую и методическую поддержку со стороны специалистов НЭИКОН.

Transcript levels of complement regulatory proteins (CD35 and CD59) in rheumatoid arthritis patients and their relationship with disease activity and prognosis

Event Abstract Back to Event Transcript levels of complement regulatory proteins (CD35 and CD59) in rheumatoid arthritis patients and their relationship with disease activity and prognosis Devyani Anand1, Maumita Kanjilal2, Satbir Kaur2, Uma Kumar2 and Nibhriti Das1* 1 All India Institute of Medical Sciences (AIIMS), Biochemistry, India 2 All India Institute of Medical Sciences (AIIMS), Medicine, India Objectives: Complement regulatory proteins (CRPs) protect the host from tissue injury mediated by activated complement system. In rheumatoid arthritis (RA) exaggerated complement activation is the key event, due to which CRPs CD35 and CD59 may influence the disease pathology and prognosis. Therefore, we aimed at elucidating the leukocyte-CD35 (L-CD35) and L-CD59 transcript levels and the relationship of these two CRPs with the disease activity of RA patients. Methods: 66 controls and 45 RA patients were recruited for this study. Out of 45 RA patients, 11 patients volunteered for the longitudinal study. L-CD35 and L-CD59 transcript levels were determined by real-time PCR and correlated with Circulating immune complexes (CIC) levels and Disease Activity Score-28 (DAS28). Results: Transcript levels of L-CR1 (p < 0.05) and L-CD59 (p < 0.01) were lowered in patients as compared to controls. In longitudinal study, L-CR1 transcript levels (p < 0.05) increased in patients which responded to treatment which correlated with lowered CIC levels (p < 0.05) and DAS28 scores (p < 0.05) at W24 as compared to W0. No significant difference was observed for L-CR1 transcript levels in non-responder group and for L-CD59 transcript levels in responder and non-responder group at W24 as compared to W0. Conclusions: This is the first study to assess the L-CR1 and L-CD59 transcript levels in RA patients. The findings indicate an intimate relation of L-CD35 transcript levels with the disease activity and prognosis in RA patients, and thus suggest L-CD35 transcript as a potential disease marker in RA. Keywords: Rheumatoid arthritis, complement regulatory proteins, Circulating immune complexes, prognosis, disease marker Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Immune-mediated disease pathogenesis Citation: Anand D, Kanjilal M, Kaur S, Kumar U and Das N (2013). Transcript levels of complement regulatory proteins (CD35 and CD59) in rheumatoid arthritis patients and their relationship with disease activity and prognosis. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00379 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 22 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Nibhriti Das, All India Institute of Medical Sciences (AIIMS), Biochemistry, New Delhi, Delhi, 110029, India, nibhriti@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Devyani Anand Maumita Kanjilal Satbir Kaur Uma Kumar Nibhriti Das Google Devyani Anand Maumita Kanjilal Satbir Kaur Uma Kumar Nibhriti Das Google Scholar Devyani Anand Maumita Kanjilal Satbir Kaur Uma Kumar Nibhriti Das PubMed Devyani Anand Maumita Kanjilal Satbir Kaur Uma Kumar Nibhriti Das Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

A systematic review of serum biomarkers anti-cyclic citrullinated Peptide and rheumatoid factor as tests for rheumatoid arthritis.

This systematic review assesses the current status of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) tests in the diagnosis and prognosis of rheumatoid arthritis (RA). We reviewed publications on tests and biomarkers for early diagnosis of RA from English-language MEDLINE-indexed journals and non-MEDLINE-indexed sources. 85 publications were identified and reviewed, including 68 studies from MEDLINE and 17 non-MEDLINE sources. Anti-CCP2 assays provide improved sensitivity over anti-CCP assays and RF, but anti-CCP2 and RF assays in combination demonstrate a positive predictive value (PPV) nearing 100%, greater than the PPV of either of the tests alone. The combination also appears to be able to distinguish between patients whose disease course is expected to be more severe and both tests are incorporated in the 2010 ACR Rheumatoid Arthritis Classification Criteria. While the clinical value of anti-CCP tests has been established, differences in cut-off values, sensitivities and specificities exist between first-, second- and third-generation tests and harmonization efforts are under way. Anti-CCP and RF are clinically valuable biomarkers for the diagnosis and prognosis of RA patients. The combination of the two biomarkers in conjunction with other clinical measures is an important tool for the diagnosis and management of RA patients.

The role of TNF.ALPHA.-induced adipose-related protein (TIARP) in TNF.ALPHA. dependent arthritic model-GPI-induced arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease with a variable disease outcome, and is characterized with synovitis, erosive changes of the joints, pain and functional deficit. Etiology is unknown. In the pathogenesis of rheumatoid arthritis the key role have proinflammatory cytokines, particularly, tumour necrosis factor (TNFalpha). The prognosis of RA patients has improved significantly during recent years, after the introduction of TNFalpha-based therapy. Despite the wide use of these biologics, their precise mechanisms of action in RA remain unclear. In the K/BxN mice, glucose-6-phosphate isomerase (GPI) is an autoantigen recognized by T and B cells. Recombinant GPI immunization to DBA/1 mice also induced acute severe arthritis. This arthritis was clearly controlled by anti-TNFalpha Abs, suggesting similar etiology to RA. In this study, to understand the mechanisms of arthritis that was regulated by TNFalpha, we focused on TNFalpha-induced adipose-related protein (TIARP) in the generation of GPI-induced arthritis.

Interstitial lung disease in rheumatoid arthritis

Interstitial lung disease (ILD) is a frequent manifestation of rheumatoid arthritis (RA), and it has a close bearing on the prognosis of RA patients. Computed tomography (CT) has been shown to be excellent for the diagnosis of diffuse lung disease. In this study chest radiographs and high-resolution CT (HRCT) scans were obtained in 91 patients with RA to evaluate their ILD precisely. By HRCT 43 patients could be diagnosed as having interstitial pneumonitis (IP), and 5 could be diagnosed as having bronchiolitis. The remaining 43 patients were normal by HRCT. Chest radiographic findings were consistent with the HRCT findings in approximately 50% of patients with IP. HRCT was superior to chest radiographs for the detection of early interstitial changes. The histogram of HRCT values might be a useful adjunct to HRCT diagnosis by adding some degree of objectivity. HRCT is useful for the diagnosis of ILD in patients with RA.