Search for: rheumatoid arthritis methotrexate autoimmune disease biomarker gene expression GWAS HLA genes non-HLA genes
ID | PMID | Title | PublicationDate | abstract |
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27542839 | The effects of dopamine receptor 2 expression on B cells on bone metabolism and TNF-α lev | 2016 Aug 19 | BACKGROUND: Dopamine receptor 2 (DR2) expressions on B cells from Rheumatoid arthritis (RA) patients has been found to be negatively correlated with disease activity and can potentially predict the response to treatment. This study aimed to investigate the role of B cell DR2 expression on bone remodeling in RA. METHODS: Patients with RA (n = 14) or osteoarthritis (OA; n = 12), and healthy controls (n = 12) were recruited for this study. Dopamine receptor (DR) 2 expression was assessed using flow cytometry. Pro-inflammatory cytokines, including interleuin(IL)-1β, IL-6, IL-17, and tumor necrosis factor(TNF)-α, and bone turnovers, including osteocalcin (OC),serum procollagen type I N propeptide (PINP), C-terminal telopeptide of type I collagen (β-CTX), collagen type I cross-linked telopeptide (ICTP), as well as matrix metalloproteinase-3 (MMP-3) and osteoprotegerin (OPG) were measured by electrochemiluminescence, chemiluminescence, or enzyme-linked immunosorbent assay. DR2 expression on synovial B cells from 4 RA patients and 3 OA patients was detected by immunofluorescence. RESULTS: There were more DR2(+)CD19(+) B cells in synovial tissues from RA patients than in those from OA patients. The frequency of peripheral B cells that expressed DR2 was positively correlated with plasma TNF-α level. Levels of ICTP and MMP-3 were significantly higher, and OPG were lower in RA patients compared to those in the OA group and healthy controls (all P < 0.05). CONCLUSION: The frequency of B cells that expressed DR2 showed a correlation with levels of the pro-inflammatory cytokine TNF-α. DR2(+)CD19(+) B cells in synovial tissues might have a role in bone metabolism and TNF-α production. | |
27981813 | B cell autoimmunity and bone damage in rheumatoid arthritis. | 2016 Dec 16 | Rheumatoid arthritis (RA) is a chronic immune-inflammatory disease associated with significant bone damage. Pathological bone remodeling in RA is primarily driven by persistent inflammation. Indeed, pro-inflammatory cytokines stimulate the differentiation of bone-resorbing osteoclasts and, in parallel, suppress osteoblast function, resulting in net loss of bone. Abating disease activity thus remains the major goal of any treatment strategy in patients with RA. Autoantibody-positive patients, however, often show a rapidly progressive destructive course of the disease, disproportionate to the level of inflammation. The epidemiological association between RA-specific autoantibodies, in particular anti-citrullinated protein autoantibodies, and poor structural outcomes has recently found mechanistic explanation in the multiple roles that B cells play in bone remodeling. In this review, we will summarize the substantial progress that has been made in deciphering how B cells and autoantibodies negatively impact on bone in the course of RA, through both inflammation-dependent and independent mechanisms. | |
27080399 | Cost-effectiveness of adalimumab for rheumatoid arthritis in Germany. | 2016 Dec | BACKGROUND: In Germany, the clinical use of TNF-α inhibitors in the therapy of rheumatoid arthritis (RA) grew from 2 % of treated patients in 2000 to 20 % in 2008. In 2012, adalimumab was the bestselling drug in the statutory health insurance system with net expenditure of € 581 mio. OBJECTIVES: We aim to analyze the cost-effectiveness of adalimumab for the treatment of RA in Germany. METHODS: We set up an individual patient sampling lifetime model to simulate 10,000 hypothetical patients. The patients' functional status improves according to American College of Rheumatology response criteria. In each 6‑month cycle, treatment might be discontinued due to loss of efficacy or adverse events. RESULTS: In the base case, patients gain 7.07 quality-adjusted life years (QALYs) with conventional synthetic therapy and 9.92 QALYs if adalimumab combination therapy is added to the treatment algorithm. The incremental cost-utility ratio (ICUR) is € 24,492 based on German list prices. After deducting mandatory rebates and taxes, the ICUR is € 17,277, comparing favorably to analyses in other countries. Adalimumab combination therapy lowers indirect costs from € 162,698 to € 134,363. The ICUR based on total costs is € 14,550 (€ 7,335 after deducting taxes and rebates). Sensitivity analysis shows that adalimumab combination therapy becomes a dominant treatment option for younger baseline populations, i. e. adalimumab is both more effective and less expensive for baseline age 30 due to savings in indirect costs. CONCLUSIONS: Our complex probabilistic model shows that estimation of cost-effectiveness for RA relies on the incorporation of indirect costs and a sufficiently long simulation horizon to capture the complete range of possible outcomes and the associated long-term benefits of biological treatment. | |
30299018 | [Comorbidity in rheumatoid arthritis: A focus on cardiovascular diseases]. | 2016 | Cardiovascular diseases (CVD) in patients with rheumatoid arthritis (RA) are ranked first in the structure of comorbidity and mortality. This review includes recent data on common pathogenic mechanisms of inflammation and atherosclerosis, the impact of traditional and specific risk factors, biomarkers of CVD in RA patients. Variants of CVD in RA, the possible pathogenic mechanisms of their development and methods of diagnosis and prevention are described. | |
27028097 | The relation between ischemia modified albumin levels and carotid intima media thickness i | 2019 Jan | BACKGROUND: Cardiovascular diseases, among which atherosclerotic heart disease, are known to be one of the most important mortality and morbidity causes in patients with rheumatoid arthritis (RA). Ischemia modified albumin (IMA) is a potential marker that can be used to assess atherosclerosis-related myocardial ischemia. Another frequently used marker for the assessment of atherosclerotic lesions is the carotid intima media thickness (CIMT). AIM: To evaluate the role that IMA has on atherosclerosis development and its clinical usability in patients with RA, by assessing the values of IMA and CIMT. METHODS AND MATERIALS: Our prospective study was conducted between June 2012 and March 2013 at the Rheumatology Department of Necmettin Erbakan Meram Medical School, Turkey. Fifty-two RA patients, diagnosed according to the 1987 criteria of the American College of Rheumatology, and an age- and sex-matched control group of 46 healthy subjects were included in this study. RESULTS: No significant difference was detected between the groups with respect to age, sex and body mass index. In the patient group the IMA and CIMT values were found to be 0.37 ± 0.12 absorbance units (ABSU) and 0.80 ± 0.22 mm, respectively, while in the control group they were 0.31 ± 0.11 ABSU and 0.51 ± 0.18 mm, respectively. The IMA and CIMT values were significantly higher in the patient group (P = 0.022 and P < 0.0001, respectively). A positive correlation was found between IMA, CIMT and Disease Activity Score of 28 joints (P = 0.016 and P = 0.002, respectively). CONCLUSION: Since the values of IMA were higher in the patient group compared to controls and because of its correlation with CIMT, we suggest the use of IMA as an early marker of atherosclerosis in RA patients. | |
26166492 | Signs of forefeet joint synovitis have a limited impact on patient's perception of rheumat | 2016 | OBJECTIVES: To determine the prevalence and distribution of signs of synovitis in the residual joints in remission defined by the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) rheumatoid arthritis (RA) remission criteria and the role of their components in preventing misclassification due to reduced joint count. METHODS: The cross-sectional observational data of RA patients including full joint counts were analyzed. Definitions of remission used were the ACR/EULAR RA remission criteria and their modifications using full joint counts with the same thresholds of the items and the calculated results. RESULTS: A total of 304 RA patients with 3,149 observations could be analyzed. Patients in remission according to the ACR/EULAR remission criteria can still show residual disease activity in the feet in up to 27% of the population with a 28-joint count remission. Residual disease activity has no impact on patient's global assessment for current disease activity, when signs of concomitant ankle joint synovitis were absent. CONCLUSIONS: RA patients in remission according to the ACR/EULAR definitions can still show signs of synovitis mostly in the forefeet joints. Acute-phase reactants and patient's global assessment for current disease activity have little impact in mitigating the limitation of reduced joint count. | |
26138387 | Risk factors for the rapid increase in risk of acute coronary events in patients with new- | 2015 Nov | OBJECTIVE: To investigate risk factors for acute coronary syndrome (ACS) in patients with new-onset rheumatoid arthritis (RA). METHODS: We performed a nested case-control study of patients with incident RA included in the Epidemiological Investigation of RA study. Cases with ACS were identified using Swedish national health registers and matched with up to 5 controls without ACS, based on incidence density-based sampling. Information on potential exposures (clinical disease activity, serologic features, genetic markers, comorbidities, pharmacotherapies, and sick leave) was collected from medical charts and register-based sources. RESULTS: We identified 138 cases and 624 controls. Smoking, history of myocardial infarction, and >50 days of sick leave the year following RA onset were associated with an increased risk of ACS. Area under the curve measurements of C-reactive protein level, erythrocyte sedimentation rate, Disease Activity Score in 28 joints (DAS28), and global health in the upper tertile during the first year and the complete followup period were both strongly associated with an increased risk of ACS. Treatment with disease-modifying antirheumatic drugs did not alter the ACS risk, nor did the presence of rheumatoid factor (RF) or shared epitope alleles, whereas high anti-citrullinated protein antibody (ACPA) levels were borderline significantly associated with ACS risk. CONCLUSION: In this study of risk factors for ACS in incident RA, clinical markers of inflammatory activity, disease activity, and total number of days of sick leave and disability pension during the first year following RA onset were identified as ACS risk factors. We found no association with RF, which was previously linked to cardiovascular disease risk in RA, but there was a borderline significant association with high ACPA levels. | |
26466969 | Immunological evaluation of rheumatoid arthritis patients treated with itolizumab. | 2016 | Rheumatoid arthritis is an autoimmune disease characterized by joint inflammation that affects approximately 1% of the general population. Itolizumab, a monoclonal antibody specific for the human CD6 molecule mainly expressed on T lymphocytes, has been shown to inhibit proliferation of T cells and proinflammatory cytokine production in psoriasis patients. We have now assessed the immunological effect of itolizumab in combination with methotrexate in rheumatoid arthritis by analyzing clinical samples taken from 30 patients enrolled in a clinical trial. T and B cell subpopulations were measured at different time points of the study. Plasma cytokine levels and anti-idiotypic antibody response to itolizumab were also evaluated. The combined treatment of itolizumab and methotrexate led to a reduction in the frequency of T cell subpopulations, and plasma levels of proinflammatory cytokines showed a significant decrease up to at least 12 weeks after treatment ended. No anti-idiotypic antibody response was detected. These results support the relevance of the CD6 molecule as a therapeutic target for the treatment of this disease. | |
30512577 | [Psoriatic arthritis, a difficult diagnosis due to clinical polymorphism]. | 2016 May | Psoriatic arthritis, a difficult diagnosis due to clinical polymorphism. Psoriatic arthritis (PsA) is a chronic inflammatory spondyloarthritis that occurs in combination with psoriasis. The prevalence is similar to rheumatoid arthritis. The diagnosis is difficult because the disease is heterogeneous, involving skin, nails and different musculoskeletal structures. There are no pathognomonic serological marker. Psoriasis usually appears 5-10 years before PsA, although some patients presents with PsA without psoriasis. TNF inhibitors (tumor necrosis factor: biological agents) have revolutionized therapy for PsA; there are effective against all disease characteristics, however not all patients achieve clinically meaningful responses and some may respond initially but lose treatment responses over time. With a better understanding of immunological mechanisms underlying psoriasis and PsA, new therapies have been developed to target specific components of the inflammatory pathway. IL17-17A and IL23 inhibitors agents (Th 17-IL17A pathway) has been shown to be efficacious. PsA is associated with a premature mortality, increased cardio vascular morbidity, obesity, metabolic syndrome. Collaboration between rheumatologist, dermatologist and general practitioner for the evaluation of morbidities, is be necessary in managing patients with PsA. | |
27919205 | Achieving simplified disease activity index remission in patients with active rheumatoid a | 2017 Sep | OBJECTIVE: To verify predictive validity of simplified disease activity index (SDAI) remission for subsequent functional and structural outcomes in real-world clinical settings under a treat-to-target strategy (T2T). METHODS: In this multicenter, prospective cohort study, T2T was implemented in rheumatoid arthritis (RA) patients with moderate-to-high disease activity. SDAI or clinical disease activity index (CDAI) was assessed every 12 weeks, and treatment was adjusted to achieve clinical remission or low disease activity (LDA). Multivariate logistic regression models were used to examine the associations of SDAI remission (≤3.3) at week 24 with the health assessment questionnaire-disability index (HAQ-DI) ≤ 0.5 or with the delta van der Heijde-modified total Sharp score (ΔvdH-mTSS)  | |
25800214 | Clocking in: chronobiology in rheumatoid arthritis. | 2015 Jun | Circadian rhythms are of crucial importance for cellular and physiological functions of the brain and body. Chronobiology has a prominent role in rheumatoid arthritis (RA), with major symptoms such as joint pain and stiffness being most pronounced in the morning, possibly mediated by circadian rhythms of cytokine and hormone levels. Chronobiological principles imply that tailoring the timing of treatments to the circadian rhythm of individual patients (chronotherapy) could optimize results. Trials of NSAID or methotrexate chronotherapy for patients with RA suggest such an approach can improve outcomes and reduce adverse effects. The most compelling evidence for RA chronotherapy, however, is that coordinating the timing of glucocorticoid therapy to coincide with the nocturnal increase in blood IL-6 levels results in reduced morning stiffness and pain compared with the same glucocorticoid dose taken in the morning. Aside from optimizing relief of the core symptoms of RA, chronotherapy might also relieve important comorbid conditions such as depression and sleep disturbances. Surprisingly, chronobiology is not mentioned in official guidelines for conducting RA drug registration trials. Given the imperative to achieve the best value with approved drugs and health budgets, the time is ripe to translate the 'circadian concept' in rheumatology from bench to bedside. | |
25295921 | Preference of surgical procedure for the forefoot deformity in the rheumatoid arthritis pa | 2015 May | OBJECTIVES: The deformed rheumatoid forefoot may be treated with resection of lesser metatarsal heads combined with arthrodesis or resection of the first metatarsophalangeal joint. Recurrent hallux valgus deformity has been reported by resection. We performed a prospective, randomized, internal-controlled study to compare results between arthrodesis and resection. METHODS: We resected the lesser metatarsal heads bilaterally and performed arthrodesis of the first metatarsophalangeal joint on one side and resection on the opposite side. We investigated 26 patients (52 feet) who were followed at least one year. Patients were assessed for clinical score, hallux valgus angle (HVA), angle between first and second metatarsals, and angle between first and fifth metatarsals preoperatively, postoperatively and at final follow-up. We evaluated callosities, claw toes, recurrences, and procedure preferences. RESULTS: The mean follow-up period was 4.1 years. No significant differences between arthrodesis and resection were seen, with the exception of HVA. That was significantly less on arthrodesis side (11.5°) than on resection side (17.0°, p < 0.05). Seven callosities on resection side and four on arthrodesis side were observed. On resection side, hallux valgus deformity often recurred (15.3%). Patients expressed a significant preference for arthrodesis over resection (p = 0.008). CONCLUSIONS: Arthrodesis provides better results for maintaining HVA. | |
26829377 | Unfolded protein response gene GADD34 is overexpressed in rheumatoid arthritis and related | 2016 | Growth arrest and DNA damage-inducible gene 34 (GADD34) is an inducible cofactor of protein phosphatase 1, which has an important role in the unfolded protein response. GADD34 has been shown to be necessary for type I interferon and proinflammatory cytokine production in response to viral infection in murine models. We investigate the expression of GADD34 in rheumatoid arthritis (RA), in which proinflammatory cytokines have an important pathogenic role. The objective of this study was to evaluate the potential of GADD34 expression as a biomarker in RA patients. We report a case-control study on GADD34 gene expression in peripheral blood mononuclear cells of patients (n = 75) with RA and age- and sex-matched healthy controls (n = 25). The study was approved by the relevant local ethics committees. GADD34 gene expression level in peripheral blood mononuclear cells was measured by quantitative PCR and analyzed with Mann-Whitney test. The relation between GADD34 gene overexpression and clinical or biological characteristics was analyzed with univariate and multivariate analysis. GADD34 gene expression was significantly higher in RA patients compared with healthy controls (p ≤ 0.001). Interestingly, GADD34 overexpression in PBMC of patients was related to the presence of circulating anti-citrullinated protein antibodies (p = 0.030). Data of this study strengthen the evidence of an unfolded protein response during the course of RA and provide an insight of the potential interest in GADD34 as a relevant marker for RA. | |
25155859 | Indicators of walking speed in rheumatoid arthritis: relative influence of articular, psyc | 2015 Jan | OBJECTIVE: To explore the contributions from and interactions between articular swelling and damage, psychosocial factors, and body composition characteristics on walking speed in rheumatoid arthritis (RA). METHODS: RA patients underwent the timed 400-meter long-corridor walk. Demographics, self-reported levels of depressive symptoms and fatigue, RA characteristics, and body composition (using whole-body dual X-ray absorptiometry, and abdominal and thigh computed tomography) were assessed and their associations with walking speed explored. RESULTS: A total of 132 RA patients had data for the 400-meter walk, among whom 107 (81%) completed the full 400 meters. Significant multivariable indicators of slower walking speed were older age, higher depression scores, higher reported pain and fatigue, higher swollen and replaced joint counts, higher cumulative prednisone exposure, nontreatment with disease-modifying antirheumatic drugs, and worse body composition. These features accounted for 60% of the modeled variability in walking speed. Among specific articular features, slower walking speed was primarily correlated with large/medium lower-extremity joint involvement. However, these articular features accounted for only 21% of the explainable variability in walking speed. Having any relevant articular characteristic was associated with a 20% lower walking speed among those with worse body composition (P < 0.001), compared with only a 6% lower speed among those with better body composition (P = 0.010 for interaction). CONCLUSION: Psychosocial factors and body composition are potentially reversible contributors to walking speed in RA. Relative to articular disease activity and damage, nonarticular indicators were collectively more potent indicators of an individual's mobility limitations. | |
27638722 | Genetic markers as therapeutic target in rheumatoid arthritis: A game changer in clinical | 2016 Nov | Rheumatoid arthritis (RA) is a chronic, inflammatory, multi-systemic autoimmune disease unremitted by genetic and environmental factors. The factors are crucial but inadequate in the development of disease; however, these factors can be representative of potential therapeutic targets and response to clinical therapy. Insights into the contribution of genetic risk factors are currently in progress with studies querying the genetic variation, their role in gene expression of coding and non-coding genes and other mechanisms of disease. In this review, we describe the significance of genetic markers architecture of RA through genome-wide association studies and meta-analysis studies. Further, it also reveals the mechanism of disease pathogenesis investigated through the mutual findings of functional and genetic studies of individual RA-associated genes, which includes HLA-DRB1, HLA-DQB1, HLA-DPB1, PADI4, PTPN22, TRAF1-C5, STAT4 and C5orf30. However, the genetic background of RA remains to be clearly depicted. Prospective efforts of the post-genomic and functional genomic period can travel toward real possible assessment of the genetic effect on RA. The discovery of novel genes associated with the disease can be appropriate in identifying potential biomarkers, which could assist in early diagnosis and aggressive treatment. | |
27060082 | Identification of citrullinated peptides in the synovial fluid of patients with rheumatoid | 2016 Sep | The objective of the study is to investigate potential citrullinated autoantigens as targets of anti-citrullinated protein antibodies (ACPAs) response in synovial fluids (SFs) of patients with rheumatoid arthritis (RA). SFs from six RA patients and six osteoarthritis (OA) patients as controls were collected. The citrullinated proteins in SFs were extracted by immunoprecipitation with rabbit anti-citrulline antibodies. Matrix-assisted laser desorption/ionization time of flight mass spectrometry/time of flight mass spectrometry (MALDI-TOF/TOF) mass spectrometry was subsequently performed to discover a characteristic neutral loss to finally determine citrullinated autoantigens. A total of 182 citrullinated peptides and 200 citrullinated sites were identified in RA SFs, while 3 citrullinated peptides and 4 citrullinated sites were identified in OA SFs. The 182 citrullinated peptides from RA SFs and the 3 citrullinated peptides from OA SFs were derived from 83 and 3 autoantigens, respectively. Eighty-three autoantigens except protein-arginine deiminase type-2 (PADI2) and protein-arginine deiminase type-2 (PADI4) were over-citrullinated compared with controls, and the citrullinated sites of PADI2 and PADI4 were different in two groups. Interestingly, citrullinated histone H3.3 (H3F3A) was found in OA controls, but not in RA groups. The differential citrullinated proteins identified in RA SFs suggested potential autoantigens were targeted for ACPAs response and might contribute to the induction and perpetuation of complement activation and joint inflammation in RA. | |
27080123 | Self-reported flares are predictors of radiographic progression in rheumatoid arthritis pa | 2016 Apr 14 | BACKGROUND: Disease flares are common in rheumatoid arthritis (RA) and are related to structural damage. However, few data on the impact of flares reported by patients on radiographic progression are available. Our aim was to investigate whether overall flares (OF), self-reported flares (SRF) and short flares assessed at the visit (SF) predict radiographic progression in RA patients in DAS28 (28-joint disease activity score) remission. METHODS: We reviewed the records of RA patients included in our database. We considered all patients who had a period of at least 24 months in remission (DAS28 < 2.6), stable biologic and synthetic disease-modifying anti-rheumatic drug treatment, no missing follow-up visits and hands and feet radiographs at the start and at the end of the 24-month follow up. Radiographic progression was considered as an increase in the van der Heijde modified total Sharp score >0. Patients were assessed every 3 months and flares were recorded. We defined SRF as any worsening of the disease reported by patients occurring in the time between visits and SF as an increase in DAS28 ≥ 2.6 or >0.6 from the previous visit assessed by the physician in one isolated visit. The impact of SRF, SF and OF on radiographic progression was assessed through multivariate regression analysis. RESULTS: One hundred forty-nine patients were included. The median number (interquartile range) of OF was 1.00/year (0.50; 1.38), of SRF was 0.50/year (0.14; 1.00), and of SF was 0.34/year (0; 0.50). Eighteen patients (12.1 %) experienced a progression of radiographic damage. OF and SRF were significant predictors of radiographic progression: OR 3.27, 95 % CI 1.30, 8.22 and OR 3.63, 95 % CI 1.16, 11.36, respectively. CONCLUSIONS: OF and SRF are predictors of structural damage. Flares assessed at the visit, SF, do not impact on radiographic progression as they might underestimate the actual number of flares. | |
26394529 | Calciphylaxis associated with rheumatoid arthritis: Communication of another case. | 2016 May | Calciphylaxis has been defined as tissue sensitivity to calcification, described mainly in patients with chronic renal insufficiency, renal transplant, or parathyroid dysfunction. There are few cases described in patients with rheumatoid arthritis that do not suffer from renal failure or hyperparathyroidism. Another case is presented of calciphylaxis in a woman with inactive rheumatoid arthritis. | |
26375339 | Evaluation of central and peripheral corneal thicknesses in patients with rheumatoid arthr | 2015 Jul | PURPOSE: To evaluate central corneal thickness (CCT) and peripheral corneal thickness (PCT) in patients with rheumatoid arthritis (RA) and to assess the relationships among the corneal parameters, dry eye disease, and clinical variables of RA. METHODS: A total of 58 RA patients and 58 control subjects participated in this study. A detailed ophthalmological examination was performed on each subject. Dry eye evaluation was performed using Schirmer's test, tear break-up time (TBUT), corneal fluorescein staining, and Ocular Surface Disease Index (OSDI). Corneal thickness at the apex point, the center of the pupil, the thinnest point, and PCT (3 mm from the apex to the superior, inferior, nasal, and temporal locations) were evaluated using Scheimpflug imaging (Pentacam®). Additionally, the relative peripheral index (RPI) was calculated by dividing the PCT by the CCT. The disease severity and quality of life were evaluated with DAS28 and HAQ, respectively. The laboratory evaluation comprised ESR and CRP. RESULTS: The mean corneal thicknesses at the apex point, the center of the pupil, the thinnest point, and the superior, inferior, nasal, and temporal points were significantly thinner in RA patients than controls. Schirmer's test scores and TBUT were significantly lower, and corneal staining and OSDI scores were significantly higher in RA patients. There were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests. CONCLUSION: The CCT and PCT were thinner in RA patients compared to those in control subjects. However, there were no significant correlations between the corneal parameters and the clinical variables of RA or dry eye tests. | |
27038800 | Carbamylated vimentin represents a relevant autoantigen in Latin American (Cuban) rheumato | 2016 Jun | Smoking produces substances that activate proinflammatory, prothrombotic and vasoconstrictive mediators via posttranslational carbamylation of proteins. As a new consequence of carbamylation, induction of anti-carbamylated autoantibodies were observed in rheumatoid arthritis (RA) patients, sometimes prior to onset of the disease. The overall aim of this study was to characterize the reactivity of different isotypes of autoantibodies against carbamylated antigens of vimentin in relation to established rheumatoid factor (RF), anti-citrullinated protein antibodies (ACPA) and markers of disease activity in a so far largely uncharacterized population of Latin American (Cuban) patients with RA. Antigenic properties of carbamylated vimentin as well as vimentin peptides were analyzed in 101 patients with RA, 50 disease controls and 51 healthy controls. The diagnostic performance was compared with established commercial ELISA rheumatoid factor, anti-cyclic citrullinated peptide antibodies of second generation (anti-CCP2) and anti-mutated citrullinated vimentin (anti-MCV) antibodies. Prevalence of anti-MCV IgG (86 %), anti-carbamylated vimentin (carbVIM) IgG (77 %) and anti-carbamylated MCV (carbMCV) IgG antibodies (65 %) was higher than the classical RF IgM (60 %) and anti-CCP2 IgG (52 %) in this RA cohort. Of note, smoking status was associated with positive IgG antibody reactivity against CCP2 in 75.0 % and against MCV in 90 % of patients. Furthermore, IgM antibody response against carbMCV and carbVIM was observed in 80 and 90.0 % of smokers, respectively. Due to a high sensitivity of the IgM antibody isotype of anti-carbVIM of 85.2 %, the combination of ACPA with anti-carbVIM IgM provided the best diagnostic performance so far achieved in a RA cohort of this ethnic origin. We demonstrate a high prevalence of anti-carbVIM antibodies and correlation with smoking in Latin American (Cuban) RA patients. Anti-carbVIM IgM represents an useful marker in ACPA-negative patients and, in combination with ACPA IgG assays, optimizes the strategy for autoantibody testing. |