Browse

Search for: rheumatoid arthritis    methotrexate    autoimmune disease    biomarker    gene expression    GWAS    HLA genes    non-HLA genes   

ID PMID Title PublicationDate abstract
25631308 A validation study of a new classification algorithm to identify rheumatoid arthritis usin 2015 Jan 28 OBJECTIVES: To develop and validate a new algorithm to identify patients with rheumatoid arthritis (RA) and estimate disease prevalence using administrative health databases (AHDs) of the Italian Lombardy region. DESIGN: Case-control and cohort diagnostic accuracy study. METHODS: In a randomly selected sample of 827 patients drawn from a tertiary rheumatology centre (training set), clinically validated diagnoses were linked to administrative data including diagnostic codes and drug prescriptions. An algorithm in steps of decreasing specificity was developed and its accuracy assessed calculating sensitivity/specificity, positive predictive value (PPV)/negative predictive value, with corresponding CIs. The algorithm was applied to two validating sets: 106 patients from a secondary rheumatology centre and 6087 participants from the primary care. Alternative algorithms were developed to increase PPV at population level. Crude and adjusted prevalence estimates taking into account algorithm misclassification rates were obtained for the Lombardy region. RESULTS: The algorithms included: RA certification by a rheumatologist, certification for other autoimmune diseases by specialists, RA code in the hospital discharge form, prescription of disease-modifying antirheumatic drugs and oral glucocorticoids. In the training set, a four-step algorithm identified clinically diagnosed RA cases with a sensitivity of 96.3 (95% CI 93.6 to 98.2) and a specificity of 90.3 (87.4 to 92.7). Both external validations showed highly consistent results. More specific algorithms achieved >80% PPV at the population level. The crude RA prevalence in Lombardy was 0.52%, and estimates adjusted for misclassification ranged from 0.31% (95% CI 0.14% to 0.42%) to 0.37% (0.25% to 0.47%). CONCLUSIONS: AHDs are valuable tools for the identification of RA cases at the population level, and allow estimation of disease prevalence and to select retrospective cohorts.
27149469 Association of Rheumatoid Arthritis and Hepatitis B Infection: A Nationwide Nested Case-Co 2016 May Rheumatoid arthritis (RA) is a disorder with altered immunologic function and increased risks of infection, while the association between HBV and RA remains largely unknown.To determine the prevalence and risk of HBV infection in patients with RA, 2 cohort datasets were sourced from Taiwan's National Health Insurance Research Database to capture National Health Insurance claims data between 1999 and 2009. One set was a specially requested RA subject's dataset extracted from the whole 23 million beneficiaries, and a total of 38,969 aged ≧18 years RA subjects were identified (RA cohort). The other one was a randomly selected 1 million patients' longitudinal dataset, and from which an additional 701,476 aged ≧18 years non-RA subjects were identified (non-RA cohort). An epidemiological approach was used to compare the prevalence and risk for HBV infection between RA and non-RA subjects.During the followed interval between 1999 and 2009, 3260 in RA cohort and 63,588 in non-RA cohort had a diagnosis of HBV infection. The annual age- and sex-standardized prevalence of HBV infection in the RA cohort was generally higher than that in the non-RA cohort. The RA patients had a higher HBV period prevalence than did the non-RA subjects (RA vs. non-RA = 69.9 vs. 60.1 cases per 1000 subjects). Compared with the non-RA cohort, the RA cohort had an increased risk of HBV infection after adjustment for potential prognostic factors (1.13, 95% CIs: 1.08-1.17).RA patients are characterized by an increased risk of HBV infection than non-RA subjects.
27182695 PADI4 Polymorphisms in Iranian Patients with Rheumatoid Arthritis. 2016 Oct AIM: Rheumatoid arthritis (RA) is a chronic autoimmune disease which affects many tissues and organs, but majorly attacks synovial joints. Beyond the major histocompatibility complex (MHC) genes, Peptidyl arginine deiminase type IV (PADI4) has been suggested to be associated with RA susceptibility. Evidence regarding the association of PADI4 single nucleotide polymorphisms (SNP) and RA is controversial, thus we conducted this large-scale case-control study to assess the association of rs874881 and rs11203367 PADI4 SNPs with susceptibility to RA. MATERIALS AND METHODS: Study population (including 665 RA patients and 392 sex-, age-, and ethnicity-matched healthy controls) were enrolled from Rheumatology Research Center of Tehran University of Medical Sciences, Shariati hospital. RESULTS: Allele or genotype frequencies of the investigated PADI4 SNPs were not different between RA patients and healthy subjects; genotypes (expressed as odds ratios) of rs11203367 [TT 0.98 (0.68-1.4), CT 0.93 (0.71-1.24), P value > 0.05] and rs874881 [CC 1.02 (0.71-1.46), CG (0.70-1.39), p value > 0.05] did not affect RA risk. Disease severity score DAS28, RF and anti-CCP antibodies of RA patients were not different between various genotypes of PADI4 SNPs. CONCLUSIONS: These findings were similar for haplotypes and diplotypes of rs11203367 and rs874881 PADI4 SNPs. In conclusion, in this case-control study with sufficient sample size to detect associations, we observed that PADI4 SNPS rs11203367 and rs874881 do not significantly determine RA susceptibility; which is in line with studies of some European populations. It seems RA pathogenesis might be different among various ethnicities, which encourage us to consider these differences in developing therapeutic interventions for management of patients.
25311255 Analysis of associations between polymorphisms within genes coding for tumour necrosis fac 2015 Mar INTRODUCTION: Despite the fact that therapy with TNF-α inhibitors constitutes a breakthrough in rheumatoid arthritis management, no improvement is still achieved in approximately 30% of cases. The aim of the study was to evaluate whether single nucleotide polymorphisms (SNPs) within the TNF-α and TNF receptor encoding genes affect the efficacy of therapy with TNF-α inhibitors in patients with RA. METHODS: Five SNPs within the TNF-α and TNF receptor encoding genes (TNFA: G-308A, G-238A, C-857T; TNFR1A G36A; TNFR1B T676G) were determined in 280 RA patients who had been treated with TNF-α inhibitors for at least 6 months or they stop therapy because of adverse events. The association between the relative change in DAS28 and SNP genotypes was tested by linear regression. RESULTS: At week 24, low disease activity or remission was achieved by 45% of the patients. After 6 months remission of the disease or low disease activity were more frequently observed among patients homozygous for the TNFR1A 36A allele than among those who were GG homozygotes (52% vs. 34%, P=0.04). At week 24 DAS28 was significantly lower in the subgroup of patients homozygous for the TNFA-857T variant compared to the C allele carriers (P=0.045). The other polymorphisms were not found to be significantly associated with EULAR response at week 12 and 24 of the anti-TNF treatment. CONCLUSIONS: Homozygosity for the TNFR1A 36A allele and the TNFA-875T variant could act as a genetic factor associated with better response to anti-TNF treatment.
25822296 First diagnosis of rheumatoid arthritis in a patient with temporomandibular disorder: a ca 2015 Mar Rheumatoid arthritis (RA) is a chronic disease of unknown etiology, characterized by synovitis of the diarthroidal joints, gradual bone erosion, and cartilage destruction. Temporomandibular joint (TMJ) arthritis is frequent in patients with RA, but it is seldom the first joint to be affected. This report presents a case of a female patient with undiagnosed RA who first presented with signs and symptoms of the disease in the TMJs. It highlights the importance of professional awareness and provides a roadmap for clinical and radiologic examination followed by biochemical and genetic monitoring for early diagnosis of RA.
27729062 Screening for peptides targeted to IL-7Rα for molecular imaging of rheumatoid arthritis s 2016 Oct 12 BACKGROUND: Interleukin-7 receptor alpha (IL-7Rα) represents a biomarker with potential applications in rheumatoid arthritis (RA) diagnosis and therapy. We have therefore searched by phage display potential IL-7Rα specific peptides with the primary goal being to develop in vivo molecular imaging tools. METHODS: IL-7Rα-targeted peptides were searched within a disulfide-constrained combinatorial phage displayed library of random linear heptapeptides. The apparent dissociation constant (K(d)) and half maximal inhibition constant (IC(50)) were estimated for phage clones and synthesized peptides by ELISA. We used 5-Aza-2'-deoxycytidine (ADC)-stimulated Jurkat cells and human synovial tissue from patients with RA for in vitro characterization of peptides. For molecular imaging studies performed by magnetic resonance imaging (MRI), experimental arthritis was induced in DBA/1 male mice by immunization with an emulsion of complete Freund's adjuvant and type II collagen from chicken sternal cartilage. RESULTS: After several steps of phage display and peptide screening, two IL-7Rα-specific heptapeptides (P258 and P725) were selected from the initial library, based on their affinity for the target (extracellular domain of IL-7Rα, which contains a fibronectin type III repeat-like sequence). P258 (a linear peptide obtained by removing the Cys-constraint) had the lowest affinity for fibronectin itself and was therefore proposed for molecular imaging. After grafting to ultra-small superparamagnetic particles of iron oxide (USPIO), P258 produced a strong negative contrast on MRI in mice with collagen-induced arthritis (CIA), even at 2 hours post injection. The co-localization of USPIO-P258 with IL-7Rα-expressing cells in the synovial tissue from CIA mice and its ability to discriminate the level of IL-7R expression and the disease severity confirmed its efficacy as an in vivo IL-7Rα imaging agent. Interestingly, the cyclic peptide (P725), which was less adequate for molecular imaging because of higher affinity for fibronectin, had a strong ability to compete with IL-7 for the IL-7Rα binding sites, making it a potential candidate for blocking applications. Accordingly, P725 prevented the signal transducer and activator of transcription 5 (STAT5) activation induced by IL-7 in ADC-stimulated Jurkat cells. CONCLUSIONS: The two peptides identified in this work demonstrate that IL-7Rα targeting in RA presents potential applications for in vivo molecular imaging and putative blocking purposes.
26276965 Longterm Safety of Rituximab: Final Report of the Rheumatoid Arthritis Global Clinical Tri 2015 Oct OBJECTIVE: Final evaluation of the longterm safety of rituximab (RTX) in rheumatoid arthritis (RA) up to 11 years. METHODS: Pooled observed case analysis of data from patients with moderate to severe, active RA in a global clinical trial program. RESULTS: As of September 2012, 3595 patients received a mean of 4 courses (range 1-20) of RTX over 11 years [14,816 patient-years (PY)]. Of these, 1246 patients had > 5 years of followup (8970 PY). A pooled placebo population (n = 818) was included in the analysis. The overall serious infection event (SIE) rate was 3.76/100 PY (2.71/100 PY in patients observed for > 5 yrs) and comparable with rates reported previously at 9.5 years (3.94/100 PY and 3.26/100 PY, respectively). SIE rates continued to be similar before and during/after development of low immunoglobulin levels, and serious opportunistic infections remained rare. Rates of cardiac events remained consistent with previous analysis and with rates in the general RA population. No increased risk of malignancy over time was observed. CONCLUSION: This final report demonstrates that RTX remains well tolerated over time and multiple courses. No new safety risks were identified and there was no increase in the rate of any types of adverse events with prolonged exposure to RTX during 11 years of observation.
26242470 Subcutaneous nodules are associated with cardiovascular events in patients with rheumatoid 2015 Oct Subcutaneous nodules are the most common conspicuous extra-articular manifestation of rheumatoid arthritis (RA). Cardiovascular disease (CVD) is the leading cause of death in patients with RA. The objective of this study is to examine the possibility of a relationship between subcutaneous nodules and "first ever" cardiovascular disease event, i.e., myocardial infarction (MI), stroke, or cardiovascular death in a large registry-cohort of patients with RA. Patient information was collected from the CORRONA registry from October 2001 to September 2011. A total of 26,042 patients with RA were studied for the presence or absence of subcutaneous nodules. Cox proportional hazards regression models were constructed to estimate the hazard ratios (HR) for CVD events in relation to subcutaneous nodules at baseline. Three statistical models were used to examine the association between subcutaneous nodules and CVD: Model A adjusted for age and sex associated risk, model B adjusted for traditional CV risk factors, and model C adjusted for factors in models A and B plus underlying RA-specific measures. The definition of primary exposure was "subcutaneous nodules at baseline." A total of 3908 patients had subcutaneous nodules at baseline. Of the 566 total composite CVD events, 138 occurred in the group that had SCN at baseline. Incidence rate-ratio values (patients with subcutaneous nodules at baseline vs. no subcutaneous nodules at baseline) for composite CVD events, MI, stroke, and cardiovascular death were 1.55, 1.65, 1.37, and 1.68, respectively. Adjusted HR values (95 % CI) for composite CVD events based on "subcutaneous nodules-status at baseline" (primary exposure) were as follows: 1.35 (1.11-1.63) for model A, 1.25 (1.03-1.52) for model B, and 1.03 (0.831-1.277) for model C. Subcutaneous nodules were associated with increased CVD events in RA. This association persisted after adjusting for age, sex, and traditional CV risk factors.
26453102 Influence of CD94 and NKG2A variants on susceptibility to rheumatoid arthritis and efficac 2016 Jan OBJECTIVES: The present study aimed to investigate relationships between the CD94 and NKG2A gene polymorphisms and the risk of rheumatoid arthritis (RA) development as well as their association with the response to anti-TNF therapy. METHODS: A total of 284 patients with RA receiving anti-TNF therapy and 124 healthy subjects were enrolled to the study. Genotypings for CD94 (rs2302489) and NKG2A (rs7301582, rs2734440, rs2734414) polymorphisms were performed using a polymerase chain reaction (PCR) amplification employing LightSNiP assays (TIB-MolBiol, Berlin, Germany). Clinical response was evaluated at 12th and 24th week after initiation of the therapy according to the EULAR response criteria. RESULTS: The frequency of the CD94 AA genotype was significantly decreased in RA patients compared to controls (OR=0.44; P=0.016). The CD94 AA homozygotes were also more common among patients negative to anti-cyclic citrullinated peptide (anti-CCP) antibodies (OR=11.28; P=0.001) as compared to anti-CCP-positive patients and the presence of the CD94 allele A was associated with lack of anti-CCP antibodies (OR=5.00; P=0.0005). The CD94 rs2302489 TT genotype was over-represented in patients exhibiting worse EULAR response at 12th week (OR=3.33; P=0.017). Furthermore, the lack of response after 12 weeks was more frequent among patients carrying the NKG2A rs7301582C allele (OR=3.68; P=0.019) or the CC genotype (OR=3.58; P=0.035) in comparison to allele T or CT/TT genotypes, respectively. CONCLUSIONS: These results indicate that CD94 and NKG2A polymorphisms may contribute to genetic susceptibility to RA or affect the response to anti-TNF therapy in patients of Caucasian origin.
25903822 Red cell distribution width: a measure of cardiovascular risk in rheumatoid arthritis pati 2015 Jun This study aims to evaluate if myocardial infarction (MI) is more frequent in rheumatoid arthritis (RA) patients with elevated levels of red cell distribution width (RDW). Utilizing a secure cloud based platform, Explorys, we searched de-identified US patient data between 1999 and 2014. RA patients were identified by serologic positivity and ICD9 diagnosis code. Patients were stratified into high (≥15.6 %) RDW and low (<13.5 %) RDW groups (and excluding any patient with prior episode of RDW >15.6 %). The proportion of patients with diagnosis of MI in each RDW group was collected. For comparison, patients were divided into high and low CRP groups (≥2.5 and ≤0.8 mg/dL) and high and low ESR groups (≥50 and ≤30 mm/h), and MI data were collected. Statistical comparison between high and low laboratory test groups was performed with chi-square test, and odds ratios were calculated. The patient population included 20,810 patients with RA. The proportion of RA patients with MI was significantly increased in the high compared to low RDW, ESR, and CRP groups (p < 0.001 for each). The odds ratios of MI were greater in the high than in the low group for each parameter: RDW (OR1.5, 95 % CI 1.3 to 1.6); ESR (OR2.0, 95 % CI 1.8-2.3); and CRP (OR1.9, 95 % CI 1.7 to 2.2). These data from a large unselected population suggest that elevated RDW levels in RA patients should prompt physicians to aggressively screen and treat their patients for modifiable cardiovascular (CVS) risk factors, in addition to treating RA inflammation.
23614783 Expectations of new treatment in rheumatoid arthritis: developing a patient-generated ques 2015 Oct BACKGROUND: Service-user partnerships in research exist in mental health, but there have been few advances in other disciplines, apart from cancer. OBJECTIVES: To develop a patient-generated expectancy measure for new treatments in rheumatoid arthritis (RA), using a participatory method. METHOD: Stage 1: three repeated focus groups and two expert panels with patients with RA conducted by a patient researcher to generate items for the draft questionnaire. Stage 2: feasibility study of draft scale with consecutive outpatient attendees. RESULTS: Patients identified 21 dimensions of new treatment expectations, grouped into (i) physical, (ii) psycho-social and (iii) expectations relating to the impact of treatment. This resulted in a draft instrument assessed in a feasibility study. DISCUSSION AND CONCLUSION: The participatory research method was useful in involving patients actively in research and to produce collaboratively a feasible, valid and acceptable measure in RA. The scale will be included in a longitudinal observational study, with newly diagnosed patients, to assess (i) whether the new scale demonstrates sensitivity to change for expectations when receiving new treatment and (ii) participants' completion rate of the new scale compared with five instruments included in the future study.
26081876 Characteristics of regulatory B10 cells in patients with rheumatoid arthritis with differe 2015 Sep In the present study, the frequency and function of B10 cells in patients with rheumatoid arthritis (RA) was examined. A total of 24 healthy controls and 97 patients with RA were enrolled in the present study. Among the 75 patients with an active disease status, 51 patients received either no treatment or were treated with non‑steroidal anti‑inflammatory drugs (NSAIDs) only, while 24 patients underwent a disease relapse. Flow cytometry was used to assess the frequency of CD19(+)CD24(hi)CD38(hi) interleukin (IL)‑10(+) cells stimulated by lipopolysaccharide plus CD40L for 48 h, followed by re‑stimulation with phorbol myristate acetate and ionomycin for 5 h. The correlation of CD19(+)CD24(hi)CD38(hi)IL‑10(+)‑cell frequency with clinical/laboratory characteristics and with levels of inflammatory cytokines were assessed along with the effects of CD19(+)CD24(hi)CD38(hi) cells on the proliferation and tumor necrosis factor α expression of CD3+ T cells. The median frequency of IL‑10‑competent cells among the CD19+ B cells was significantly increased among patients with RA with active disease. However, a sub‑group of patients with a high disease status that received no treatment/NSAIDs exhibited a significantly lower frequency (≤1% IL‑10+ B cells). These patients exhibited longer symptom duration, a greater number of tender and swollen joints and a higher patient global visual analogue scale and disease activity score in 28 joints‑C reactive protein. Functional assays further demonstrated that B10 cells from the sub‑group with ≤1% IL‑10+ B cells secreted significantly lower levels of IL‑10 and exerted a significantly decreased suppressive effect on CD3+ T-cell proliferation and tumor necrosis factor‑α production. The frequency and functional heterogeneity of B10 cells in patients with RA at different disease stage suggested that further investigation on the underlying mechanism of the generation and function of B10 cells in patients with RA is required prior to use in clinical practice.
27698637 Extensor Indicis Proprius Tenodesis to Correct Finger Ulnar Drift Deformity in Rheumatoid 2016 Sep Background: The most frequent deformity of the hand occurring in patients with RA affects the metacarpophalangeal (MCP) joint and it is characterized by a volar subluxation of the proximal phalanges and ulnar drift of the fingers. Methods: The Extensor Indicis Proprius (EIP) tenodesis for correction of ulnar deviation of fingers (II to V) was performed in 10 hands (40 fingers and 5 patients). Results: There was complete correction of the subluxation or dislocation and almost complete correction of the ulnar drift of the metacarpophalangeal joints at the initial postoperative evaluation (three to four months after surgery). However, at final evaluation (eight to twelve months after the operation), all of the digits had some recurrence of ulnar deviation. Conclusion: The EIP tenodesis provides a correct forces vector to maintain the fingers in proper alignment following correction of ulnar deviation.
26787370 IFI44L promoter methylation as a blood biomarker for systemic lupus erythematosus. 2016 Nov OBJECTIVE: Systemic lupus erythematosus (SLE) is a clinically heterogeneous disease with limited reliable diagnostic biomarkers. We investigated whether gene methylation could meet sensitivity and specificity criteria for a robust biomarker. METHODS: IFI44L promoter methylation was examined using DNA samples from a discovery set including 377 patients with SLE, 358 healthy controls (HCs) and 353 patients with rheumatoid arthritis (RA). Two independent sets including 1144 patients with SLE, 1350 HCs, 429 patients with RA and 199 patients with primary Sjögren's syndrome (pSS) were used for validation. RESULTS: Significant hypomethylation of two CpG sites within IFI44L promoter, Site1 (Chr1: 79 085 222) and Site2 (Chr1: 79 085 250; cg06872964), was identified in patients with SLE compared with HCs, patients with RA and patients with pSS. In a comparison between patients with SLE and HCs included in the first validation cohort, Site1 methylation had a sensitivity of 93.6% and a specificity of 96.8% at a cut-off methylation level of 75.5% and Site2 methylation had a sensitivity of 94.1% and a specificity of 98.2% at a cut-off methylation level of 25.5%. The IFI44L promoter methylation marker was also validated in an European-derived cohort. In addition, the methylation levels of Site1 and Site2 within IFI44L promoter were significantly lower in patients with SLE with renal damage than those without renal damage. Patients with SLE showed significantly increased methylation levels of Site1 and Site2 during remission compared with active stage. CONCLUSIONS: The methylation level of IFI44L promoter can distinguish patients with SLE from healthy persons and other autoimmune diseases, and is a highly sensitive and specific diagnostic marker for SLE.
27857093 Rheumatoid arthritis - an update for general dental practitioners. 2016 Nov 18 Rheumatoid arthritis (RA) is a common chronic inflammatory autoimmune disorder which significantly impacts patients' lives and can lead to permanent disability. Inflammation in RA not only affects joints; but can affect organs including the heart and lungs. Early diagnosis, initiation of intensive drug therapy, and a multidisciplinary care approach have vastly improved the long-term prognosis for those living with the condition. However, RA patients often present with co-morbidities which add to the complexity of clinical management. Orofacial conditions associated with RA which dental professionals need to be aware of include periodontal disease, temporomandibular dysfunction and salivary gland dysfunction. In this article, we provide information on RA, oral health in RA and guidance on how best to manage patients with RA in general dental practice.
25173349 Economic evaluation of a brief education, self-management and upper limb exercise training 2015 Feb OBJECTIVE: The aim of this study was to conduct a cost-utility analysis of the Education, Self-management and Upper Limb Exercise Training in People with RA (EXTRA) programme compared with usual care. METHODS: A within-trial incremental cost-utility analysis was conducted with 108 participants randomized to either the EXTRA programme (n = 52) or usual care (n = 56). A health care perspective was assumed for the primary analysis with a 36 week follow-up. Resource use information was collected on interventions, medication, primary and secondary care contacts, private health care and social care costs. Quality-adjusted life years (QALYs) were calculated from the EuroQol five-dimension three-level (EQ-5D-3L) questionnaire responses at baseline, 12 and 36 weeks. RESULTS: Compared with usual care, total QALYs gained were higher in the EXTRA programme, leading to an increase of 0.0296 QALYs. The mean National Health Service (NHS) costs per participant were slightly higher in the EXTRA programme (by £82), resulting in an incremental cost-effectiveness ratio of £2770 per additional QALY gained. Thus the EXTRA programme was cost effective from an NHS perspective when assessed against the threshold of £20 000-£30 000/QALY gained. Overall, costs were lower in the EXTRA programme compared with usual care, suggesting it was the dominant treatment option from a societal perspective. At a willingness-to-pay of £20 000/QALY gained, there was a 65% probability that the EXTRA programme was the most cost-effective option. These results were robust to sensitivity analyses accounting for missing data, changing the cost perspective and removing cost outliers. CONCLUSION: The physiotherapist-led EXTRA programme represents a cost-effective use of resources compared with usual care and leads to lower health care costs and work absence. TRIAL REGISTRATION: International Standard Randomized Controlled Trial Number Register; http://www.controlled-trials.com/isrctn/ (ISRCTN14268051).
26227989 Local Joint inflammation and histone citrullination in a murine model of the transition fr 2015 Nov OBJECTIVE: Anti-citrullinated protein antibodies (ACPAs) are characteristic of rheumatoid arthritis (RA). However, their presence years before the onset of clinical RA is perplexing. Although multiple putative citrullinated antigens have been identified, no studies have demonstrated the specific capacity of these antigens to initiate inflammatory arthritis. This study was undertaken to recapitulate the transition from preclinical to clinical RA and to demonstrate the capacity of local citrullination to facilitate this transition. METHODS: We performed proteomic analysis of activated human neutrophils to identify citrullinated proteins, including those targeted as part of the RA immune response. Using enzyme-linked immunosorbent assay, we compared RA and osteoarthritis synovial fluid for levels of citrullinated histone H2B and its immune complex. Using macrophage activation assays, we assessed the effect of histone citrullination on immunostimulatory capacity and evaluated the stimulatory capacity of native and citrullinated H2B immune complexes. Finally, we assessed the potential for anti-citrullinated H2B antibodies to mediate arthritis in vivo. RESULTS: We identified robust targeting of neutrophil-derived citrullinated histones by the ACPA immune response. More than 90% of the RA patients had anti-citrullinated H2B antibodies. Histone citrullination increased innate immunostimulatory capacity, and immune complexes containing citrullinated histones activated macrophage cytokine production and propagated neutrophil activation. Finally, we demonstrated that immunization with H2B was arthritogenic, but only in the setting of underlying articular inflammation. CONCLUSION: Our findings indicate that citrullinated histones, specifically citrullinated H2B, are an antigenic target of the ACPA immune response. Furthermore, local generation of citrullinated antigen during low-grade articular inflammation provides a mechanistic model for the conversion from preclinical autoimmunity to inflammatory arthritis.
27655512 Cytokine genotype distribution in patients with periodontal disease and rheumatoid arthrit 2016 Jul The association between oral and systemic health has highlighted the importance of periodontal health and treatment, with the consequence that dental assessment and attention to oral hygiene have assumed an increasingly important part in the clinical management of patients with diabetes mellitus and rheumatoid arthritis. The aim of this work was to assess genotype frequencies in polymorphisms of genes of IL-1α-889 and IL-1β-511 in a case-controlled study population of patients affected by periodontal disease and rheumatoid arthritis or diabetes mellitus.
26339445 Wild-type ATTR amyloidosis of the ureter in a 56-year-old woman with rheumatoid arthritis 2015 We present a case of acute pyelonephritis with right hydronephrosis in a middle-aged woman, who had suffered from rheumatoid arthritis and Sjögren's syndrome. She had successfully treated with antibiotics, however, ureteral stenosis sustained. She underwent ureteroscopy and stenting of right ureter. Biopsy specimen revealed submucosal amyloid deposition in the interstitium overlying a benign urothelium. Amyloid protein was positive for transthyretin (TTR) by immunohistochemistry and amyloid deposition was not demonstrated in other organs. The patient's TTR genes were wild type and she was diagnosed with wild-type ATTR (ATTR wt) amyloidosis. This is the first report about symptomatic ATTR wt amyloidosis, which was also called 'systemic senile amyloidosis (SSA)' in the ureter. We should aware that SSA can occur at younger age and cause symptomatic ureteral stenosis. Further investigation is needed to clarify the association of autoimmune diseases to develop ATTR wt amyloidosis.
26258819 Habitual Physical Activity, Sedentary Behaviour and Bone Health in Rheumatoid Arthritis. 2015 Nov Associations between habitual physical activity levels and bone health in rheumatoid arthritis (RA) were assessed. Twenty nine female patients with RA were assessed for bone mineral density (BMD), and classified as having low or normal hip BMD. Habitual physical activity levels were assessed using accelerometry, and disease activity was assessed using the Clinical Disease Activity Index (CDAI). Twenty one patients had normal bone mass, while 8 had low bone mass. There was no difference in age in the normal bone mass group (51(8)) compared to the low bone mass group (57(12)), p=0.19. Patients with normal bone mass spent on average 2 h less per day in sedentary activity (65(4)% vs. 73(2)%, p<0.01), over 70 min more time in light activity (23(1)% vs. 18(2)%, p<0.01), and over 50 min more in moderate activity per day (12(3)% vs. 8(2)%, p<0.01) than did patients with low bone mass, independently of disease activity or duration. Patients with normal bone mass broke up their sedentary time more frequently per day (72(21) vs. 53(18) times per day, p=0.03). The results of this study indicate that higher habitual activity levels may be protective of bone health in patients with RA, and should be encouraged.