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ID PMID Title PublicationDate abstract
23190565 Demographics, clinical characteristics and predictive factors for total knee or hip replac 2013 Mar OBJECTIVES: This paper aims to study the prevalence of total knee and hip replacements in Greek patients with rheumatoid arthritis (RA) and to identify possible predictive factors for future total hip or knee replacement. METHODS: A retrospective medical record review was performed in 750 RA patients who were recruited during 1994 to 2008 in a single Greek medical centre. Of the reviewed patients, 489 with a minimum follow-up duration of 1 year were enrolled in the study. The occurrence of total hip or knee replacement was used as the primary outcome variable in the predictive analysis. RESULTS: Total hip or knee replacement associated with RA was performed in 21 patients (4.3%). Total disease duration was the most significant factor associated with increased likelihood of total joint replacement. Erythrocyte sedimentation rate (ESR) at baseline examination was positively associated with subsequent knee or hip joint replacement (OR=1.023, 95%CI 1.005-1.04). Inadequate response to treatment was associated with a 3.12-times higher likelihood of joint replacement (95%CI, 1.28-7.58). The patients who underwent total hip or knee replacement had significantly higher ESRs and DAS 28 levels (p<0.046 and p<0.002, respectively) after the first year of follow-up. CONCLUSIONS: The identification of factors associated with total joint hip or knee replacement can improve pharmacological treatment to maintain function and prevent destruction of the affected joints. Longer disease duration and inadequate response to treatment after the first year of follow-up increases the likelihood ratio for total joint replacement during the course of disease in Greek RA patients.
25336464 Depletion of B-cells with rituximab improves endothelial function and reduces inflammation 2014 Oct 21 BACKGROUND: Individuals with rheumatoid arthritis (RA) are at increased risk for cardiovascular disease, partly due to systemic inflammation and endothelial dysfunction. B-cells play an important pathogenic role in the inflammatory process that drives RA disease activity. Rituximab, a chimeric murine/human monoclonal antibody that depletes B-cells, is an effective therapy for RA. The purpose of this study was to determine whether B-cell depletion with rituximab reduces systemic inflammation and improves macrovascular (brachial artery flow-mediated dilation, FMD) and microvascular (reactive hyperemia) endothelial function in RA patients. METHODS AND RESULTS: RA patients received a single course of rituximab (1000 mg IV infusion at baseline and on day 15). FMD, reactive hyperemia, inflammatory markers, and clinical assessments were performed at baseline, week 12, and week 24. Twenty patients (95% female, median age 54 years) completed the study. Following treatment, FMD improved from a baseline of 4.5±0.4% to 6.4±0.6% at 12 weeks (mean±SE; P<0.0001), followed by a decline at week 24; a similar pattern was observed for hyperemic velocity. Significant decreases in RA disease scores, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, and circulating CD19+ B-cells were sustained through week 24. Cholesterol and triglycerides became significantly although modestly elevated during the study. CONCLUSIONS: Depletion of B-cells with rituximab improved macrovascular and microvascular endothelial function and reduced systemic inflammation, despite modest elevation in lipids. Given these results, rituximab should be evaluated in the future for its possible role in reducing excess cardiovascular risk in RA. CLINICAL TRIAL REGISTRATION: URL http://ClinicalTrials.gov. Unique identifier: NCT00844714.
25287961 Effects of adalimumab treatment on endothelial cell activation markers in the skeletal mus 2014 Nov OBJECTIVES: Patients with rheumatoid arthritis (RA), particularly those with severe disease, have increased risk of cardiovascular disease (CVD). Previous studies suggest that endothelial cell activation may contribute to this co-morbidity, and that treatment with tumour necrosis factor (TNF) inhibitors could reduce the risk of CVD in these patients. The aim of this study was to investigate endothelial cell activation markers in muscle tissue of patients after adalimumab treatment. METHODS: Patients with active RA who started treatment with adalimumab 40 mg every two weeks were included. Muscle biopsies taken before and 3 months after start of treatment were available from 11 patients (9 females, mean age 54.2 years, median disease duration 6.5 years, 91% anti-CCP positive, 7 on methotrexate [median dose 20 mg/week]). None of the patients had clinical signs of myopathy. IL-1α and HLA-DQ were investigated by immunohistochemistry. Quantification was performed by computer assisted image analysis. RESULTS: Disease activity, measured by DAS28 decreased (mean 5.5 vs. 4.1; p=0018). A good or moderate EULAR response was seen in 6/11 patients. HLA-DQ was mainly expressed in endothelial cells in capillaries, whereas IL-1α was mainly seen in larger vessels. HLA-DQ expression decreased significantly after treatment (p=0.041). There was a similar trend for IL-1α, in particlar in EULAR good/moderate responders. CONCLUSIONS: Adalimumab treatment was associated with decreased expression of endothelial markers previously associated with severe systemic inflammation in RA. Our findings indicate a reduced endothelial activation in patients treated with anti-TNF drugs, which might contribute to a lower risk of cardiovascular co-morbidity.
25474157 Fears and beliefs in rheumatoid arthritis and spondyloarthritis: a qualitative study. 2014 OBJECTIVES: To explore beliefs and apprehensions about disease and its treatment in patients with rheumatoid arthritis and spondyloarthritis. METHODS: 25 patients with rheumatoid arthritis and 25 with spondyloarthritis participated in semi-structured interviews about their disease and its treatment. The interviews were performed by trained interviewers in participants' homes. The interviews were recorded and the main themes identified by content analysis. RESULTS: Patients differentiated between the underlying cause of the disease, which was most frequently identified as a hereditary or individual predisposition. In patients with rheumatoid arthritis, the most frequently cited triggering factor for disease onset was a psychological factor or life-event, whereas patients with spondyloarthritis tended to focus more on an intrinsic vulnerability to disease. Stress and overexertion were considered important triggering factors for exacerbations, and relaxation techniques were frequently cited strategies to manage exacerbations. The unpredictability of the disease course was a common source of anxiety. Beliefs about the disease and apprehensions about the future tended to evolve over the course of the disease, as did treatment expectations. CONCLUSIONS: Patients with rheumatoid arthritis and spondyloarthritis hold a core set of beliefs and apprehensions that reflect their level of information about their disease and are not necessarily appropriate. The physician can initiate discussion of these beliefs in order to dispel misconceptions, align treatment expectations, provide reassurance to the patient and readjust disease management. Such a dialogue would help improve standards of care in these chronic and incapacitating diseases.
23940212 Ultrasound definition of tendon damage in patients with rheumatoid arthritis. Results of a 2014 Nov OBJECTIVE: To develop the first ultrasound scoring system of tendon damage in rheumatoid arthritis (RA) and assess its intraobserver and interobserver reliability. METHODS: We conducted a Delphi study on ultrasound-defined tendon damage and ultrasound scoring system of tendon damage in RA among 35 international rheumatologists with experience in musculoskeletal ultrasound. Twelve patients with RA were included and assessed twice by 12 rheumatologists-sonographers. Ultrasound examination for tendon damage in B mode of five wrist extensor compartments (extensor carpi radialis brevis and longus; extensor pollicis longus; extensor digitorum communis; extensor digiti minimi; extensor carpi ulnaris) and one ankle tendon (tibialis posterior) was performed blindly, independently and bilaterally in each patient. Intraobserver and interobserver reliability were calculated by κ coefficients. RESULTS: A three-grade semiquantitative scoring system was agreed for scoring tendon damage in B mode. The mean intraobserver reliability for tendon damage scoring was excellent (κ value 0.91). The mean interobserver reliability assessment showed good κ values (κ value 0.75). The most reliable were the extensor digiti minimi, the extensor carpi ulnaris, and the tibialis posterior tendons. An ultrasound reference image atlas of tenosynovitis and tendon damage was also developed. CONCLUSIONS: Ultrasound is a reproducible tool for evaluating tendon damage in RA. This study strongly supports a new reliable ultrasound scoring system for tendon damage.
22580587 Evaluating joint destruction in rheumatoid arthritis: is it necessary to radiograph both h 2013 Mar BACKGROUND: Radiological damage is an important outcome measure in rheumatoid arthritis (RA), both for research and clinical purposes. Depending on the setting, both hands and feet are radiographed, or only a part of these. It is unknown whether radiographing part of the four extremities gives comparable information to radiographing both hands and feet. This study therefore aimed to compare the radiological information obtained both when evaluating single time point radiographs and progression over time, in early and advanced RA. METHODS: 6261 sets of hands and feet x-rays of 2193 RA patients from Leiden, Groningen (both from The Netherlands) and North America were studied. Correlations between joint damage at different regions were compared (unilateral vs bilateral and hands vs feet). Analyses were done at single time points (cross-sectional) and for progression over time (longitudinal), both for continuous severity measures (Sharp/van der Heijde score; SHS) and binomial measures of erosiveness. RESULTS: When studying single time points, the severity of joint damage (SHS) is highly correlated between left and right, but weakly correlated between hands and feet. Correlation coefficients were higher in advanced than early RA. These findings were comparable in the three datasets. When evaluating erosiveness using only unilateral x-rays or hands without feet, 19.3% and 24.0-40.4% are incorrectly classified as non-erosiveness. Similarly, when evaluating disease progression by imaging only unilateral x-rays or only hand x-rays, progression would have been missed in 11.6-16.2% and 21.2-31.0% of patients. CONCLUSION: Performing x-rays of both hands and feet yields additive information compared with imaging only a part of these.
24741597 Sonic hedgehog signaling drives proliferation of synoviocytes in rheumatoid arthritis: a p 2014 Sonic hedgehog (Shh) signaling controls many aspects of human development, regulates cell growth and differentiation in adult tissues, and is activated in a number of malignancies. Rheumatoid arthritis (RA) is characterized by chronic synovitis and pannus formation associated with activation of fibroblast-like synoviocytes (FLS). We investigated whether Shh signaling plays a role in the proliferation of FLS in RA. Expression of Shh signaling related components (Shh, Ptch1, Smo, and Gli1) in RA synovial tissues was examined by immunohistochemistry (IHC) and in FLS by IHC, immunofluorescence (IF), quantitative RT-PCR, and western blotting. Expression of Shh, Smo, and Gli1 in RA synovial tissue was higher than that in control tissue (P < 0.05). Cyclopamine (a specific inhibitor of Shh signaling) decreased mRNA expression of Shh, Ptch1, Smo, and Gli1 in cultured RA FLS, Shh, and Smo protein expression, and significantly decreased FLS proliferation. Flow cytometry analysis suggested that cyclopamine treatment resulted in cell cycle arrest of FLS in G1 phase. Our data show that Shh signaling is activated in synovium of RA patients in vivo and in cultured FLS form RA patients in vitro, suggesting a role in the proliferation of FLS in RA. It may therefore be a novel therapeutic target in RA.
25149988 TNF inhibitors - Mechanisms of action, approved and off-label indications. 2014 Oct Tumor necrosis factor inhibitors (TNFi) belong to the group of biologic drugs, holding presently top positions on lists of most profitable products for pharmaceutical companies. Although current indications for TNFi include only selected diseases with an established role of immune dysfunction in their pathogenesis, studies on new indications are being carried out all over the world. The most important aspect of TNFi therapy is a targeted therapeutic approach, allowing to avoid a wide range of side effects associated with treatment with nonspecific immunosuppressive agents. Results of the trials on TNFi in the approved indications are widely accessible and analyzed elsewhere, both in primary publications as well as in systematic reviews and meta-analyses. Here we aim to discuss their mechanisms of action, and approved, as well as off-label indications of TNFi. In addition, we present comprehensive evidence on TNFi in treatment of rheumatoid arthritis (RA); the first authorized and probably most extensively developed indication for the majority of TNFi.
24183223 Rheumatoid arthritis and erythema multiforme: a possible pathogenetic link for T-cell-medi 2013 We present a case of a woman with a 14-year history of rheumatoid arthritis, who showed simultaneously and gradually appearing, annular, erythematous, itchy patches and exacerbation of the joint symptoms, of one month duration, after pregnancy. Clinical and histologic features led us to the diagnosis of erythema multiforme. While it is not possible to exclude that the co-occurrence of the two conditions is coincidental, our case suggests the possibility that erythema multiforme is a sign of an ample alteration of the immune system that may occur in patients with systemic immune diseases as a consequence of the action of various triggering factors, such as molecular mimicry between endogenous and exogenous antigens or pregnancy, which is notoriously a period of complex and still largely unexplored alterations in the immune system reactivity.
24745172 Vascular endothelium--role in chronic inflammatory disease. 2013 The vascular endothelial lining of blood vessels plays a key 'target-effector' role in vivo, integrating the body's response to inflammatory cytokines, chemokines and growth factors (derived from both endothelial cells themselves and from other cells such as leukocytes and fibroblasts), to allow leukocyte activation, adhesion and extravasation from the flowing blood into underlying tissue. Endothelial proliferation, through the process of angiogenesis, results in an increased cell surface area for these events to occur, and further functions to deliver oxygen and nutrients, and to remove waste products. In addition to playing an important role in physiology, the endothelium is thus an active participant in inflammatory pathologies. One of the best understood diseases in which inflammation and angiogenesis play a part is rheumatoid arthritis (RA). Blockade of the inflammatory cascade in RA has significant consequences for the vasculature, highlighting the links between reducing endothelial activation and therapeutic benefit in chronic inflammatory disorders.
25442297 Criterion validity of the International Physical Activity Questionnaire Short Form (IPAQ-S 2015 Jun OBJECTIVES: The International Physical Activity Questionnaire Short Form (IPAQ-SF) is a self-report questionnaire commonly used in patients with rheumatoid arthritis (RA) to measure physical activity. However, despite its frequent use in patients with RA, its validity has not been ascertained in this population. The aim of this study was to examine the criterion validity of energy expenditure from physical activity recorded with the IPAQ-SF in patients with RA compared with the objective criterion measure, the SenseWear Armband (SWA) which has been validated previously in this population. DESIGN: Cross-sectional criterion validation study. SETTING: Regional hospital outpatient setting. PARTICIPANTS: Twenty-two patients with RA attending outpatient rheumatology clinics. INTERVENTIONS: Subjects wore an SWA for 7 full consecutive days and completed the IPAQ-SF. MAIN OUTCOME MEASURES: Energy expenditure from physical activity recorded by the SWA and the IPAQ-SF. RESULTS: Energy expenditure from physical activity recorded by the IPAQ-SF and the SWA showed a small, non-significant correlation (r=0.407, P=0.60). The IPAQ-SF underestimated energy expenditure from physical activity by 41% compared with the SWA. This was corroborated using Bland and Altman plots, as the IPAQ-SF was found to overestimate energy expenditure from physical activity in nine of the 22 individuals, and underestimate energy expenditure from physical activity in the remaining 13 individuals. CONCLUSION: The IPAQ-SF has limited use as an accurate and absolute measure for estimating energy expenditure from physical activity in patients with RA.
24743261 Anti-cyclic citrullinated Peptide antibody is associated with interstitial lung disease in 2014 OBJECTIVE: Patients with rheumatoid arthritis (RA) are at risk to develop RA-associated interstitial lung disease (RA-ILD). This retrospective study aimed to investigate the potential association of the positivity of serum anti-cyclic citrullinated peptide antibody (anti-CCP2) and rheumatoid factor (RF) with RA-ILD in RA patients. METHODS: A total of 285 RA patients were recruited at the inpatient service of Peking Union Medical College Hospital in China between 2004 and 2013. Individual patients were evaluated for the evidence of ILD. The concentrations of serum anti-CCP2 and RF in individual patients were measured. The potential risk factors for ILD in RA patients were assessed by univariate and multivariate models. RESULTS: There were 71 RA patients with RA-ILD, accounting for 24.9% in this population. The positive rates of anti-CCP2 and RF in the patients with RA-ILD were significantly higher than that in the patients with RA-only (88.7% vs. 67.3%, p<0.001; 84.5% vs. 70.6%, p = 0.02, respectively). Univariate and multivariate logistic regression analysis revealed that RA patients with positive serum anti-CCP2, but not RF, were associated with an increased risk of ILD (crude odds ratio [cOR] 3.83, 95% confidence interval [CI] 1.74-8.43, p<0.001; adjusted odds ratio [aOR] 3.50, 95% CI 1.52-8.04, p<0.001). CONCLUSION: Our findings suggest that positive serum anti-CCP2, but not RF, may be associated with RA-ILD in RA patients.
22580581 Autoantibodies to citrullinated fibrinogen compared with anti-MCV and anti-CCP2 antibodies 2013 Mar OBJECTIVES: To compare the performance of anticitrullinated peptides/protein antibodies (ACPA) detected by three immunoassays in the French ESPOIR cohort of patients with early rheumatoid arthritis (RA) and undifferentiated arthritis (UA) and to study the relationship between ACPA and disease activity. METHODS: A diagnosis of RA (1987 American College of Rheumatology (ACR) criteria) was established at baseline in 497 patients and after a 2-year follow-up in 592 patients. At baseline, antibodies to citrullinated fibrinogen (AhFibA), antimutated citrullinated vimentin (anti-MCV) and anticyclic citrullinated peptide (anti-CCP2) were assayed and the individual and combined diagnostic sensitivities and predictive values of the tests were determined. Relationships between ACPA positivity and the 28-joint disease activity score and Health Assessment Questionnaire scores were analysed. RESULTS: At a diagnostic specificity of at least 98%, the three tests exhibited similar diagnostic sensitivities (47-48.5%). When considering as positive patients with at least one positive test, the sensitivity increased to 53.5% with a probable loss of specificity. Among the patients classified as having UA at baseline, 30% were positive for one ACPA, the positive predictive values for RA of the three tests ranging from 73% to 80% but increasing when two tests were associated. Whatever the test used, the addition of ACPA positivity to the 1987 criteria enhanced their sensitivity by 6%, close to that of the 2010 ACR/European League Against Rheumatism (EULAR) criteria. CONCLUSIONS: In early arthritis, AhFibA, anti-MCV and anti-CCP2 showed similar diagnostic sensitivity with a high diagnostic specificity and a similar high positive predictive value for RA. Adding ACPA to the 1987 ACR criteria significantly increased the number of patients classified as having RA, confirming the validity of the recent inclusion of the serological criterion in the ACR/EULAR criteria.
24366391 Circulating anti-cyclic citrullinated peptide antibody in patients with rheumatoid arthrit 2014 Jul Anti-cyclic citrullinated peptide (anti-CCP) antibody is highly specific for diagnosing rheumatoid arthritis (RA). Cigarette smoking is a lifestyle and environmental factor associated with anti-CCP production and is strongly associated with chronic obstructive pulmonary disease (COPD). This study assessed levels of anti-CCP antibodies and rheumatoid factor (RF) among patients with RA and COPD. The study sample comprised 63 patients with RA and 70 patients with COPD, all of whom underwent assessment of anti-CCP antibody and RF levels. Testing revealed that 54.2% of RA patients and 0% of COPD patients were positive for anti-CCP antibodies. Additionally, 82.5% of RA patients and 42% of COPD patients were positive for RF. Among RA patients, levels of anti-CCP antibodies were higher among smokers than among nonsmokers (242.7 ± 128.3 vs. 68.1 ± 112.1, P < 0.001). COPD patients had low titers of RF but were negative for anti-CCP antibodies. The presence of anti-CCP antibodies was a reliable serologic marker in RA diagnosis and was associated with cigarette smoking.
24106520 Increased IL-33 in synovial fluid and paired serum is associated with disease activity and 2013 OBJECTIVES: IL-33, a newly found cytokine which is involved in joint inflammation, could be blocked by a decoy receptor-sST2. The expression and correlation of IL-33 and sST2 in rheumatoid arthritis (RA) are of great interest. METHODS: Synovial fluid (SF) was obtained from 120 RA and 30 osteoarthritis (OA) patients, and paired sera were collected from 54 of these RA patients. The levels of IL-33 and sST2 were measured by ELISA. RESULTS: SF IL-33 was significantly higher in RA than in OA, which was correlated with disease activity score 28, erythrocyte sedimentation rate, rheumatoid factor (RF)-IgM, RF-IgG, glucose phosphate isomerase (GPI), and immunoglobulin. Serum IL-33 was correlated positively with SF IL-33 in RA. Furthermore, it was correlated with RF-IgM and GPI. sST2 was partly detectable in RA (13 out of 54, 24.1%), while not in OA. Serum sST2 in RA had no significant correlation with serum IL-33 or SF IL-33. However, SFs from both RA and OA patients did not express sST2. CONCLUSIONS: This study supported that IL-33 played an important role in the local pathogenesis of RA. Considering the tight correlation between IL-33 and clinical features, it may become a new target of local treatment.
25427393 [Application of radiological imaging in rheumatoid arthritis]. 2014 Advancement in technology and development in the field of radiological equipment provides us with a variety of diagnostic possibilities. Once diagnosed, further grading of pathologic condition is needed in order to monitor the changes of affected joints, either progression due to the course of the disease or remission due to the applied therapy. Different methods used in imaging of musculoskeletal system are discussed, including use of standard radiography, computed tomography, magnetic resonance, ultrasound and Color Doppler imaging. Bone mineral density results add much additional data so densitometry scanning is performed routinely.
24686780 Molecular imaging with macrophage CRIg-targeting nanobodies for early and preclinical diag 2014 May An accurate and noninvasive tracer able to detect molecular events underlying the development of rheumatoid arthritis (RA) would be useful for RA diagnosis and drug efficacy assessment. A complement receptor of the Ig superfamily (CRIg) is expressed on synovial macrophages of RA patients, making it an interesting target for molecular imaging of RA. We aim to develop a radiotracer for the visualization of CRIg in a mouse model for RA using radiolabeled single-domain variable antibody VHH fragments (Nanobodies). METHODS: Quantitative polymerase chain reaction was used to locate CRIg expression in mice with collagen-induced arthritis (CIA). A Nanobody, NbV4m119, was generated to specifically target CRIg. Flow cytometry, phosphorimaging, and confocal microscopy were used to confirm NbVm119 binding to CRIg-positive cells. SPECT (SPECT/CT) was used to image arthritic lesions in the inflamed paws of 29 mice using (99m)Tc-NbV4m119 Nanobody. RESULTS: CRIg is constitutively expressed in the liver and was found to be upregulated in synovial tissues of CIA mice. SPECT/CT imaging revealed that (99m)Tc-NbV4m119 specifically targeted CRIg-positive liver macrophages in naïve wild-type but not in CRIg(-/-) (CRIg knockout) mice. In CIA mice, (99m)Tc-NbV4m119 accumulation in arthritic lesions increased according to the severity of the inflammation. In the knees of mice with CIA, (99m)Tc-NbV4m119 was found to accumulate even before the onset of macroscopic clinical symptoms. CONCLUSION: SPECT/CT imaging with (99m)Tc-NbV4m119 visualizes joint inflammation in CIA. Furthermore, imaging could predict which mice will develop clinical symptoms during CIA. Consequently, imaging of joint inflammation with CRIg-specific Nanobodies offers perspectives for clinical applications in RA patients.
24647982 Prevalence of metabolic syndrome in patients with rheumatoid arthritis in Morocco: a cross 2014 Nov Rheumatoid arthritis (RA) is associated with an increased risk for cardiovascular disease (CVD). The prevalence of metabolic syndrome (MetS)-a major contributor to CVD-in RA seems to be increased, suggesting that systemic inflammation and antirheumatic therapy may contribute to its presence. We aimed to determine the prevalence of MetS in RA, to identify the potential factors associated with its presence, and to evaluate the influence of antirheumatic drugs on the occurrence of MetS in a cohort of Moroccan patients with RA. The prevalence of MetS was assessed cross-sectionally in 179 patients with RA over a period of 17 months (July 2011-December 2012). Three definitions of MetS were used (National Cholesterol Education Program/Adult Treatment Panel III 2005, International Diabetes Federation 2005, and American Association of Clinical Endocrinologists 2003). All statistical analyses were done using the SPSS software version 18.0. Multivariate logistic regression model was constructed to identify independent predictors of MetS in patients with RA. The prevalence of MetS in RA varied from 24.6 to 30.7 % according to the definitions used. In a multivariate logistic regression model, the severity of RA and less methotrexate use were identified as significant independent predictors of the presence of MetS in RA patients. Our study suggests that MetS is common among Moroccan patients with severe RA. Methotrexate therapy was identified as an independent factor associated with a reduced risk of having MetS in these patients, suggesting a drug-specific mechanism and making methotrexate a first-line disease-modifying antirheumatic drug in RA patients who are at high risk of developing MetS.
25042612 Rheumatic diseases and the microbiome. 2014 Jun Every human is intimately associated with a large and diverse population of microorganisms living on the skin and mucous membranes. These commensal organisms are known as the microbiome, or microbiota, and are acquired in young childhood. The microbiome is critically important in establishing a fully function immune system. For example, Th17 T helper cells are not present in a germ-free environment. The relationship of the microbiome to autoimmune disease is being explored actively. Mechanisms by which the microbiome may influence these diseases include, but are not limited to, molecular mimicry as well as induction and regulation of both Th17 and regulatory T cells. There are ample data that a specific oral microbe, Porphyromonas gingivalis, the only bacteria with the enzyme peptidylarginine deiminase, is involved in the pathogenesis of rheumatoid arthritis. Connection between other rheumatic autoimmune diseases and the microbiome remains to be made.
23574525 Tyrosine kinase inhibitors for the treatment of rheumatoid arthritis. 2013 Tyrosine kinases (TK) are enzymes capable of transferring phosphate groups to tyrosine residues in cytoplasmic proteins or the intracellular domains of transmembrane receptors. TK play critical roles in diverse biological functions including cellular processes such as adhesion, motility, proliferation, cell cycle control, cell death, as well as biological functions at the whole-organism level such as growth and development, metabolism or immune defense. TK inhibitors including spleen TK (fostamatinib) and Janus kinases (tofacitinib) inhibitors are two novel oral therapies that have demonstrated short-term good clinical responses in active rheumatoid arthritis patients with and inadequate responses to methotrexate or other traditional (non-biologic) disease-modifying antirheumatic drugs (DMARDs). Those responses are comparable to responses rates from pivotal trials of TNF inhibitors. TK inhibitors are generally well tolerated but not free of adverse effects. Several side effects had been described including gastrointestinal symptoms, neutropenia, hypertension, elevated liver function test and lipid alterations among others. Owing to the limited duration of follow-up of patients treated with TK inhibitors, the long term safety profile of these drugs are unknown.