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ID PMID Title PublicationDate abstract
28115292 Cadherin-11 as a therapeutic target in chronic, inflammatory rheumatic diseases. 2017 Mar Cadherin-11 has been identified as a key regulator of synovial architecture mediating contact between Fibroblast-like Synoviocytes and organization in the lining layer. A central role for cadherin-11 has also been suggested in the formation of the rheumatoid pannus. Therapeutic targeting of cadherin-11 results in amelioration of autoimmune experimental arthritis, as well as of experimental fibrosis. In addition, cadherin-11 expression is upregulated in the synovium of patients with chronic inflammatory arthritis, whereas detection of cadherin-11 mRNA transcripts in the peripheral blood has been associated with more severe disease phenotypes in two prototypic conditions of chronic joint inflammation and fibrosis, namely, rheumatoid arthritis and systemic sclerosis, respectively. Currently, a monoclonal antibody against cadherin-11 is in early phases of clinical trials in patients with rheumatoid arthritis. Herein, we review the current knowledge regarding the potential role of cadherin-11 in pathogenesis, as well as a biomarker and therapeutic target in chronic inflammatory rheumatic diseases.
28507187 Measuring Disease Exacerbation and Flares in Rheumatoid Arthritis: Comparison of Commonly 2017 Aug OBJECTIVE: To evaluate and compare the utility of commonly used outcome measures for assessing disease exacerbation or flare in patients with rheumatoid arthritis (RA). METHODS: Data from the Dutch Potential Optimalisation of (Expediency) and Effectiveness of Tumor necrosis factor-α blockers (POET) study, in which 462 patients discontinued their tumor necrosis factor-α inhibitor, were used. The ability of different measures to discriminate between those with and without physician-reported flare or medication escalation at the 3-month visit (T2) was evaluated by calculating effect size (ES) statistics. Responsiveness to increased disease activity was compared between measures by standardizing change scores (SCS) from baseline to the 3-month visit. Finally, the incremental validity of individual outcome measures beyond the Simplified Disease Activity Score was evaluated using logistic regression analysis. RESULTS: The SCS were greater for disease activity indices than for any of the individual measures. The 28-joint Disease Activity Score, Clinical Disease Activity Index, and Simplified Disease Activity Index performed similarly. Pain and physician's (PGA) and patient's global assessment (PtGA) of disease activity were the most responsive individual measures. Similar results were obtained for discriminative ability, with greatest ES for disease activity indices followed by pain, PGA, and PtGA. Pain was the only measure to demonstrate incremental validity beyond SDAI in predicting 3-month flare status. CONCLUSION: These results support the use of composite disease activity indices, patient-reported pain and disease activity, and physician-reported disease activity for measuring disease exacerbation or identifying flares of RA. Physical function, acute-phase response, and the auxiliary measures fatigue, participation, and emotional well-being performed poorly.
28688467 Prediction of Response to Targeted Treatment in Rheumatoid Arthritis. 2017 Jul Rheumatoid arthritis is an autoimmune syndrome presenting with chronic inflammation of the joints. Patients with the same diagnosis can present with different phenotypes. In some patients severe joint inflammation and early joint destruction are observed, whereas a milder phenotype can be seen in others. Conversely, patients with the same signs and symptoms may exhibit different immunological and molecular abnormalities. Since the introduction of early treatment in clinical practice, the treat to target principle, and new medicines such as biologic disease-modifying antirheumatic drugs, clinical remission can be achieved early in the disease course, albeit not in all patients. The clinical response and efficacy of biologic disease-modifying antirheumatic drugs vary among different individuals. Therefore, there is a need to develop a more personalized approach toward treatment to achieve rapid remission in every patient to prevent disability and restore and maintain quality of life, without unnecessary adverse effects, in a cost-effective manner. The latest data from explorative studies of predictive markers of response are discussed here, together with a preliminary treatment algorithm based on currently available knowledge.
28085997 Association Between Menopausal Factors and the Risk of Seronegative and Seropositive Rheum 2017 Nov OBJECTIVE: To investigate whether menopausal factors are associated with the development of serologic rheumatoid arthritis (RA) phenotypes. METHODS: Data were analyzed from the Nurses' Health Studies (NHS; 1976-2010 and NHSII 1989-2011). A total of 120,700 female nurses ages 30-55 years in the NHS, and a total of 116,430 female nurses ages 25-42 years in the NHSII, were followed via biennial questionnaires on lifestyle and disease outcomes. In total, 1,096 incident RA cases were confirmed by questionnaire and chart review. Seropositive RA was defined as rheumatoid factor positive (RF) or antibodies to citrullinated protein antigen (ACPA) positive, and seronegative RA was defined as RF negative and ACPA negative. We used Cox proportional hazards models to obtain multivariable-adjusted hazard ratios (HRs) with 95% confidence intervals (95% CIs) of seropositive/seronegative RA associated with menopausal status, age at menopause, type of menopause, ovulatory years, and postmenopausal hormone therapy (PMH) use. RESULTS: Postmenopausal women had a 2-fold increased risk of seronegative RA, compared with premenopausal women (NHS: HR 1.8 [95% CI 1.1-3.0], NHSII: HR 2.4 [95% CI 1.4-3.9], and pooled HR 2.1 [95% CI 1.4-3.0]). Natural menopause at early age (≤44 years) was associated with an increased risk of seronegative RA (pooled HR 2.4 [95% CI 1.5-4.0]). None of the menopausal factors was significantly associated with seropositive RA. We observed no association between PMH use and the risk of seronegative or seropositive RA, except that PMH use of ≥8 years was associated with increased risk of seropositive RA (pooled HR 1.4 [95% CI 1.1-1.9]). CONCLUSION: Postmenopause and natural menopause at an early age were strongly associated with seronegative RA, but only marginally with seropositive RA, suggesting potential differences in the etiology of RA subtypes.
28952205 Characterization of neutrophil-to-lymphocyte ratio as a measure of inflammation in rheumat 2017 Oct OBJECTIVES: The neutrophil to lymphocyte ratio (NLR) is one of the well-recognized sensitive measures of inflammation. This cross-sectional observational study was aimed at characterizing the relationship of NLR with the inflammatory markers erythrocyte sedimentation rate (ESR), C-reative protein (CRP), Disease Activity Score of 28 joints (DAS28)-CRP(3), joint counts and quality measures of rheumatoid arthritis (RA). MATERIALS AND METHODS: Patients with RA were recruited in two phases. The following were assessed for all patients: joint count, pain by visual analogue scale (VAS), complete blood count, ESR, CRP and quality index assessment using the Short Form health survey (SF-36) questionnaire. A subgroup analysis was also performed to evaluate the association between NLR and cytokines. RESULTS: Four hundred and eighty-nine subjects were recruited. Distribution of NLR values corresponded with DAS28-CRP(3) rather than CRP and ESR. A significant difference in VAS, swollen joint counts (SJC-28), inflammatory parameters and general health outcome measures was observed among the NLR groups. A weak correlation was observed between NLR and RA disease measures. It had least bias at lower ranges with DAS28-CRP(3) than CRP and ESR. The NLR cut-off value of 1.4 classified the patients in deep remission with 90% specificity, 24% sensitivity, likelihood ratio positive (LR+) 2.46 and likelihood ratio negative (LR-) 0.84. CRP was a significant baseline predictor of NLR. A significant influence of interleukin-6 on CRP was noted. CONCLUSION: In contrast to the traditional markers, NLR may serve as a less expensive and effective measure of inflammation in RA. Its efficacy is comparable to that of CRP and it is not impacted by the cytokines influencing CRP and ESR.
28364628 Human adipose tissue-derived mesenchymal stem cells in rheumatoid arthritis: Regulatory ef 2017 Jun BACKGROUND AND OBJECTIVES: Mesenchymal stem cells (MSCs) are multipotent adult stem cells with immunomodulatory properties. The mechanisms by which MSCs inhibit the proliferation of pro-inflammatory T cells have not been fully elucidated yet. It is assumed that pro-inflammatory T-cells play an important role in the development of autoimmune diseases. We investigated the potential therapeutic effects of human adipose tissue derived (Ad)-MSCs on the peripheral blood mononuclear cells (PBMCs) of rheumatoid arthritis (RA) patients and healthy individuals, with a particular focus on Th17-associated cytokines. MATERIALS AND METHODS: PBMCs from RA patients and healthy donors were co-cultured with Ad-MSCs and HeLa with or without Phytohemagglutinin (PHA). Finally, IL-6, IL-17, IL-21, IL-23 and TGF-β levels were determined by ELISA and quantitative real-time RT-PCR on co-culture supernatants and PBMCs, respectively. RESULTS: In co-culture interaction, Ad-MSCs inhibited IL-17 secretion by PBMCs compared to unstimulated PBMCs cultured alone. In addition, IL-21 expressions in PBMCs of the patient group, and IL-17 and IL-21 in healthy group were inhibited by Ad-MSCs compared to PBMCs cultured alone. TGF-β expression in healthy individuals remarkably increased in both MSC-treated groups with and without PHA in comparison to PHA-stimulated and -unstimulated PBMCs. CONCLUSIONS: This study demonstrates that human Ad-MSCs act as key regulators of immune tolerance by inhibiting the inflammation. Therefore, they can be attractive candidates for immunomodulatory cell-based therapy in RA.
27989589 Efficacy of triple association methotrexate, sulfasalazine and hydroxychloroquine in early 2017 Oct OBJECTIVES: To evaluate the efficacy of the triple synthetic Disease Modifying Anti-Rheumatic Drugs (sDMARD) combination methotrexate, sulfasalazine and hydroxychloroquine versus a biologic DMARD (bDMARD) in the treatment of early rheumatoid arthritis. METHODS: A systematic literature search was performed using the PubMed and Cochrane databases, and abstracts presented at rheumatology scientific meetings until December 2013. Randomized controlled trials comparing the efficacy and the safety of biologic DMARD with the triple combination were included. Outcome measures were Van der Heijde modified Sharp score (SHS), remission rate, ACR criteria response, adverse events. RESULTS: A total of 1225 abstracts were screened. We extracted data from 5 trials including patients (515 in the triple combination group and 710 in the bDMARD group). We showed higher ACR70 response (OR=1.79, 95% CI [1.17, 2.72]) in patients treated with bDMARDs, whereas radiological progression was not different from patient with triple combination (OR=1.10, 95% CI [-0.04, 0.28]). At year 2, ACR70 response and remission rate, the results were similar in both groups with respectively OR=1.44 (95% CI [0.86, 2.43]) and SMD=0.45 (95% CI [0.17, 0.72]). The proportion of serious adverse events was similar in both groups OR=1.02 (95% CI [0.68, 1.52], P=0.92, I(2)=0%). Gastro-intestinal adverse events were higher in the triple combination group (OR=1.75, 95% CI [0.73, 4.21], P=0.21, I(2)=75%). Infectious adverse events were more frequent in the bDMARD group (OR=0.50, 95% CI [0.35, 0.70], P<0.0001, I(2)=36%). CONCLUSION: Biological treatment seems to be more efficient than triple combination in terms of radiological progression in RA with inadequate response to methotrexate.
29061443 Outcomes of lupus and rheumatoid arthritis patients with primary dengue infection: A seven 2018 Apr OBJECTIVE: We described the clinical profile and outcomes of patients with SLE and RA diseases reported to the Brazilian Health Information System with primary dengue infection. METHODS: Databases from the Brazilian Public Health Informatics System (SUS) were linked as the source of information. Three databases comprising different longitudinal information of lupus or rheumatoid arthritis (RA) patients under treatment and care through the Brazilian Health System were linked. Patients who had lupus ICD-9 code or RA ICD-9 code and their treatment approved by SUS were included in the study. In Study 1, we described the clinical characteristics of RA/lupus patients who had dengue infection. In Study 2, we compared RA/lupus patients with or without dengue for hospitalization rates after index dengue diagnosis for dengue-exposed or matching date for dengue-unexposed. RESULTS: We included 69 SLE and 301 RA patients with dengue. In the RA/lupus with dengue case series, hospitalization was found in 24.6% of lupus subjects and of 11.2% of RA subjects. It differed by geographic region (p = 0.03), gender (p = 0.05) and the use of azathioprine (p = 0.02). Dengue was the most frequent reason for hospitalization reported (43.0%). Hospitalization due to dengue was noted in 12 (42.9%) dengue-exposed patients (p = 0.02), while rheumatoid arthritis was reported as the cause of hospitalization in 22.2% of dengue-unexposed (p = 0.005). Five deaths were reported among the dengue-exposed and none among dengue-unexposed. Bacterial infection was the most frequent cause of death. We found that the dengue exposure was associated with an increased risk of hospitalization outcome in RA and lupus patients (RR = 6.2; 95% CI: 2.99-12.94). SUMMARY: We found that when comparing RA/lupus patients with or without dengue, dengue-exposed patients had an increased rates of hospitalization and death.
27932359 Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) case presentation 2017 Mar 1 Remitting seronegative symmetrical synovitis with pitting oedema (RS3PE) syndrome mainly affects elderly men and responds well to steroids. Since this syndrome can resemble other diseases, its diagnosis is a significant challenge. Through the following paper, we hope to improve the diagnosis of RS3PE by presenting a table comparing RS3PE to two other common polyarthritic conditions affecting the elderly.
28619088 Chemokine signals are crucial for enhanced homing and differentiation of circulating osteo 2017 Jun 15 BACKGROUND: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy. Receptors for osteoclastogenic factors (CD115 and receptor activator of nuclear factor-κB [RANK]) and selected chemokines (CC chemokine receptor 1 [CCR1], CCR2, CCR4, CXC chemokine receptor 3 [CXCR3], CXCR4) were determined in an OCP-rich subpopulation (CD3(-)CD19(-)CD56(-)CD11b(+)CD14(+)) by flow cytometry. In parallel, levels of CC chemokine ligand 2 (CCL2), CCL3, CCL4, CCL5, CXC chemokine ligand 9 (CXCL9), CXCL10, and CXCL12 were measured using cytometric bead array or enzyme-linked immunosorbent assay. Sorted OCPs were stimulated in culture by macrophage colony-stimulating factor and receptor activator of nuclear factor-κB ligand, and they were differentiated into mature osteoclasts that resorb bone. Selected chemokines (CCL2, CCL5, CXCL10, and CXCL12) were tested for their osteoclastogenic and chemotactic effects on circulatory OCPs in vitro. RESULTS: The OCP population was moderately enlarged among PB cells in RA and correlated with levels of tumor necrosis factor-α (TNF-α), rheumatoid factor, CCL2, and CCL5. Compared with PB, the RANK(+) subpopulation was expanded in SF and correlated with the number of tender joints. Patients with PsA could be distinguished by increased RANK expression rather than total OCP population. OCPs from patients with arthritis had higher expression of CCR1, CCR2, CCR4, CXCR3, and CXCR4. In parallel, patients with RA had increased levels of CCL2, CCL3, CCL4, CCL5, CXCL9, and CXCL10, with significant elevation in SF vs PB for CXCL10. The subset expressing CXCR4 positively correlated with TNF-α, bone resorption marker, and rheumatoid factor, and it was reduced in patients treated with disease-modifying antirheumatic drugs. The CCR4(+) subset showed a significant negative trend during anti-TNF treatment. CCL2, CCL5, and CXCL10 had similar osteoclastogenic effects, with CCL5 showing the greatest chemotactic action on OCPs. CONCLUSIONS: In our study, we identified distinct effects of selected chemokines on stimulation of OCP mobilization, tissue homing, and maturation. Novel insights into migratory behaviors and functional properties of circulatory OCPs in response to chemotactic signals could open ways to new therapeutic targets in RA.
29212384 Articular and subcutaneous adipose tissues of rheumatoid arthritis patients represent equa 2017 Dec Adipose-derived mesenchymal stem cells (ASCs) have immunoregulatory properties, but their activity is dependent on signals provided by the local microenvironment. It is likely that highly inflammatory milieu of rheumatoid joint affects ASCs activity. To test this hypothesis, the function of rheumatoid ASCs derived from articular adipose tissue (AT-ASCs) and ASCs derived from subcutaneous adipose tissue (Sc-ASCs) has been analysed. Articular adipose tissue (infrapatellar fat pad) and subcutaneous adipose tissue (from the site of skin closure with sutures) were obtained from rheumatoid arthritis (RA) patients undergoing total knee joint replacement surgery. ASCs were isolated accordingly to the routinely applied procedure, expanded and treated or not with IFNγ and TNF (10 ng/ml). To evaluate immunomodulatory properties of AT- and Sc-ASCs, co-cultures with peripheral blood mononuclear cells (PBMCs) from healthy donors have been set. Proliferation of activated PBMCs ((3)H-thymidine incorporation method), secretion of IL-10 and IL-17A in co-culture supernatants (specific ELISA tests) and T regulatory FoxP3(+) cells (Tregs) percentage have been evaluated (flow cytometry). Performed experiments demonstrated that ASCs from both sources have comparable properties. They suppress proliferation of activated PBMCs to the similar extent, induce IL-10 secretion by resting PBMCs and moderately induce generation of FoxP3(+) Treg cells. Interestingly, both AT-ASCs and Sc-ASCs cause increase of IL-17A secretion by activated PBMCs as well as induce up-regulation of IL-6 concentration in co-culture supernatants. We demonstrated that AT-ASCs and Sc-ASCs obtained from RA patients possess similar immunomodulatory properties despite different localization and distinct cytokine milieu of tissue of origin. Our results indicate that ASCs derived from rheumatoid adipose tissues are not strongly immunosuppressive in vitro and that they may contribute to the pathogenesis of RA due to IL-17A secretion enhancement.
29204683 Wide difference in biologics usage and expenditure for the treatment of patients with rheu 2018 Apr To analyze the biologics usage and expenditure for the treatment of patients with rheumatoid arthritis (RA) in each prefecture throughout Japan using the national open database, the Ministry of Health, Labour and Welfare of Japan disclosed; in Oct 2016, the data of the top 30 most-frequently prescribed drugs during a 1-year period from April 2014 to March 2015 in each prefecture in Japan, along with the patients' age and sex. Seldom-used drugs were excluded. We picked up only biologics for the present study. The total expenditure on biologics used in each prefecture was correlated with the population thereof. However, there was a big difference, up to ~ twofold, in the average expenditure used for an RA patient: highest in Toyama and lowest in Wakayama. There was also a big difference, ~ 4.5-fold, in the number of rheumatologists/1000 RA patients, highest in Kyoto and lowest in Aomori. The average expenditure used for an RA patient was correlated with the number of rheumatologists in the western part of Japan. Etanercept seemed to be used most frequently to Japanese RA patients followed closely by infliximab. Abatacept was used more frequently to the elderly than other biologics. There was a big difference in the number of rheumatologists and expenditure on biologics for the treatment of an RA patient among prefectures in fiscal 2014. Factors that brought this unevenness need to be scrutinized for universal implementation of good RA care throughout Japan, where there are uniform health insurance system and free access to rheumatologists.
29105312 Acute effect of a resistance exercise session on markers of cartilage breakdown and inflam 2017 Nov AIM: To assess the acute effect of resistance exercise (RE) on circulating biomarkers of cartilage breakdown and inflammation in women with rheumatoid arthritis (RA). METHODS: Thirty-four volunteers (17 with and 17 without RA), participated in a 25 min RE session (knee extension, knee flexion, hip abduction and hip adduction) with one set of 12 repetitions at 50% of one repetition maximum (1RM) and one set of eight repetitions at 75% of 1RM. Blood samples were collected 30 and 5 min before, immediately after and 1, 2 and 24 h after the session. We used analysis of variance for repeated-measures with Bonferroni adjustments to assess differences between groups over time. RESULTS: In both groups we found significant changes in interleukin (IL)-1 beta (P = 0.045), IL-1 receptor antagonist (IL-1ra) (P < 0.001), IL-10 (P = 0.004), IL-6 (P < 0.001) and cartilage oligomeric matrix protein (COMP) P < 0.001) in response to exercise, but no changes in tumor necrosis factor-alpha and C-reactive protein levels. We found no differences in the responses of the two groups to the session, except for COMP levels, which are more sensitive to exercise and rest effects in RA patients. CONCLUSION: Women with and without RA have similar changes in response to a RE session in levels of inflammation biomarkers, but not of cartilage breakdown. IL-10 and IL-1ra increased after the RE session, indicating that RE may have an acute anti-inflammatory effect. Additional studies are necessary to clarify if repeated RE sessions can have long-term anti-inflammatory effects and the possible clinical repercussions of this cartilage breakdown characteristic in response to exercise in RA patients.
28505104 Identification and Validation of SAA4 as a Rheumatoid Arthritis Prescreening Marker by Liq 2017 May 14 Rheumatoid arthritis (RA) is a chronic autoimmune disease that progresses into systemic inflammation and joint deformity. RA diagnosis is a complicated procedure, and early diagnostic methods are insufficient. Therefore, in this study, we attempted to identify new markers to improve the accuracy of RA prescreening. e identified differentially expressed proteins (DEPs) by using liquid chromatography tandem-mass spectrometry in health-prescreening sera with high rheumatoid factor (RF) values, and compared the findings with those from sera with normal RF values. We identified 93 DEPs; of these, 36 were upregulated, and 57 were downregulated in high-RF sera. Pathway analysis revealed that these DEPs were related to immune responses. Additionally, four DEPs were statistically analyzed by proteomic analysis; of these, SAA4 was significantly validated in individual enzyme-linked immunosorbent assays. Moreover, SAA4 was significantly upregulated in RA patients (n = 40, 66.43 ± 12.97 ng/mL) compared with normal controls (n = 40, 4.79 ± 0.95 ng/mL) and had a higher area under the curve than C-reactive protein. Thus, we identified SAA4 as a protein that was positively correlated with RF and RA. SAA4 may represent a novel prescreening marker for the diagnosis of RA.
28742266 p-Coumaric acid, a dietary polyphenol ameliorates inflammation and curtails cartilage and 2017 Sep 10 This study was designed to explore the underlying mechanism of p-coumaric acid (CA), a dietary polyphenol in adjuvant-induced arthritis (AIA) rat model with reference to synovitis and osteoclastogenesis. Celecoxib (COX-2 selective inhibitor) (5 mg/kg b.wt) was used as a reference drug. CA remarkably suppressed the paw edema, body weight loss and inflammatory cytokine and chemokine levels (TNF-α, IL-1β, IL-6, and MCP-1) in serum and ankle joint of arthritic rats. Consistently, CA reduced the expression of osteoclastogenic factors (RANKL and TRAP), pro-inflammatory cytokines (TNF-α, IL-1β, IL-6, and IL-17), and inflammatory enzymes (iNOS and COX-2) in arthritic rats. However, OPG expression was found elevated. Besides, the abundance of transcription factors (NF-κB-p65, and p-NF-κB-p65, NFATc-1, and c-Fos) and MAP kinases (JNK, p-JNK, and ERK1/2) expression was alleviated in CA administered arthritic rats. In addition, CA truncated osteoclastogenesis by regulating the RANKL/OPG imbalance in arthritic rats and suppressing the RANKL-induced NFATc-1 and c-Fos expression in vitro. Radiological (CT and DEXA scan) and histological assessments authenticated that CA inhibited TRAP, bone destruction and cartilage degradation in association with enhanced bone mineral density. Taken together, our findings suggest that CA demonstrated promising anti-arthritic effect and could prove useful as an alternative drug in RA therapeutics. © 2017 BioFactors, 43(5):698-717, 2017.
28053322 VAV1 regulates experimental autoimmune arthritis and is associated with anti-CCP negative 2017 Jan Rheumatoid arthritis (RA) patients can be stratified into two subgroups defined by the presence or absence of antibodies against citrullinated circular peptides (anti-CCP) with most of the genetic association found in anti-CCP positive RA. Here we addressed the role of VAV1, previously associated to multiple sclerosis (MS), in the pathogenesis of RA in experimental models and in a genetic association study. Experimental arthritis triggered by pristane or collagen type II was induced in DA rats and in the DA.BN-R25 congenic line that carries a polymorphism in Vav1. Difference in arthritis severity was observed only after immunization with pristane. In a case-control study, 34 SNPs from VAV1 locus were analyzed by Immunochip genotyping in 11475 RA patients (7573 anti-CCP positive and 3902 negative) and 15,870 controls in six cohorts of European Caucasians. A combination of the previous MS-associated haplotype and two additional SNPs was associated with anti-CCP negative RA (alleles G-G-A-A of rs682626-rs2546133-rs2617822-rs12979659, OR=1.13, P=1.27 × 10(-5)). The same markers also contributed to activity of RA at baseline with the strongest association in the anti-CCP negative group for the rs682626-rs12979659 G-A haplotype (β=-0.283, P=0.0048). Our study suggests a role for VAV1 and T-cell signaling in the pathology of anti-CCP-negative RA.
27125521 How well do ACPA discriminate and predict RA in the general population: a study based on 1 2017 Jan OBJECTIVE: Anti-citrullinated protein antibodies (ACPA) are highly specific for rheumatoid arthritis (RA), but the diagnostic accuracy of ACPA in the general population has not been thoroughly assessed. We aimed to assess the diagnostic accuracy of ACPA for RA in the general population and to further characterise the citrullinated peptide recognition pattern. METHODS: Serum samples from a large population-representative twin cohort consisting of 12 590 individuals were analysed for the presence of ACPA using anti-CCP2 ELISA. All ACPA-positive samples were further tested on ELISAs for four peptide-specific ACPA. RA cases were identified by linkage to the Swedish National Patient Register at inclusion and after a median follow-up of 37 months (IQR 31-49). RESULTS: 350 out of 12 590 individuals had a positive anti-CCP2 test, measuring ACPA. Of these, 103 had an RA diagnosis at the time of blood donation and inclusion. During a median follow-up of 3 years, an additional 21 of the remaining 247 ACPA-positive individuals developed RA. Overall, a positive anti-CCP2 test had a positive predictive value of 29% for prevalent RA at inclusion (negative predictive value of 99.6%). High titres (>3× cut-off) of anti-CCP2 increased the positive predictive value to 48% (negative predictive value of 99.5%). ACPA-positive individuals without RA had lower anti-CCP2 titres and fewer peptide-specific ACPA than ACPA-positive patients with RA and higher C reactive protein levels than ACPA-negative individuals without RA. CONCLUSION: Presence of ACPA and especially high titres of anti-CCP2 have a high diagnostic accuracy for an RA diagnosis in a population setting.
27723275 Subfertility in Women With Rheumatoid Arthritis and the Outcome of Fertility Assessments. 2017 Aug OBJECTIVE: Subfertility is frequently encountered among female rheumatoid arthritis (RA) patients and has been associated with disease activity and antirheumatic drugs. However, little is known about the results of the fertility assessments in these women. Our aim was to study the outcome of fertility assessments in subfertile women with RA. METHODS: A cross-sectional study was performed in a nationwide cohort of female RA patients who were pregnant or trying to conceive between 2002 and 2010 (Pregnancy-Induced Amelioration of Rheumatoid Arthritis Study). Patients who had given consent for future contact (n = 260) received a questionnaire on reproductive history, fertility examinations, and fertility treatments. Medical files were obtained from attending gynecologists. RESULTS: A completed questionnaire was returned by 178 women (68%), of whom 96% had ended their efforts to conceive. Eighty-two subjects (46%) had at least 1 subfertile episode, and for 61 women a diagnosis for subfertility was available. Unexplained subfertility (48%) and anovulation (28%) were the most common gynecologic diagnoses, and both occurred more often in RA patients than reported in the general population. Women with unexplained subfertility more often used nonsteroidal antiinflammatory drugs (NSAIDs) during the periconceptional period. Seventeen percent of all pregnancies were conceived after fertility treatments. Fertility treatments had equal or higher pregnancy rates in RA compared to other subfertile populations. CONCLUSION: Unexplained subfertility is more often diagnosed in subfertile female RA patients than in the general population, and is related to periconceptional NSAID use. Despite the higher incidence of subfertility in women with RA, the outcome of fertility treatments in these women appears favorable.
28273146 Evaluation of an automated connective tissue disease screening assay in Korean patients wi 2017 This study aimed to evaluate the diagnostic utilities of the automated connective tissues disease screening assay, CTD screen, in patients with systemic rheumatic diseases. A total of 1093 serum samples were assayed using CTD screen and indirect immunofluorescent (IIF) methods. Among them, 162 were diagnosed with systemic rheumatic disease, including rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), and mixed connective tissue disease (MCT). The remaining 931 with non-systemic rheumatic disease were assigned to the control group. The median ratios of CTD screen tests were significantly higher in the systemic rheumatic disease group than in the control group. The positive likelihood ratios of the CTD screen were higher than those of IIF in patients with total rheumatic diseases (4.1 vs. 1.6), including SLE (24.3 vs. 10.7). The areas under the receiver operating characteristic curves (ROC-AUCs) of the CTD screen for discriminating total rheumatic diseases, RA, SLE, and MCT from controls were 0.68, 0.56, 0.92 and 0.80, respectively. The ROC-AUCs of the combinations with IIF were significantly higher in patients with total rheumatic diseases (0.72) and MCT (0.85) than in those of the CTD screen alone. Multivariate analysis indicated that both the CTD screen and IIF were independent variables for predicting systemic rheumatic disease. CTD screen alone and in combination with IIF were a valuable diagnostic tool for predicting systemic rheumatic diseases, particularly for SLE.
29054459 Lymphocyte subset analysis in QuantiFERON-TB Gold Plus and T-Spot.TB for latent tuberculos 2018 Feb Rheumatoid arthritis (RA) is an immune mediated inflammatory disorder, and immune suppressive drugs are prescribed. RA patients receiving treatments are in a kind of immunosuppressive condition that presents increased risk of developing active tuberculosis. Accurate diagnosis of latent tuberculosis infection (LTBI) is recommended for RA. QuantiFERON(®)-TB Gold Plus (QFT-Plus), a novel IGRA, has two tubes (TB1 and TB2). TB2 is designed to elicit both CD4 and CD8 T-cell responses, with expected increased sensitivity. We conducted a cross-sectional study to compare two IGRAs, QFT-Plus and T-SPOT(®).TB (TSPOT), in RA. One hundred fifty-two RA patients (median age: 66.5 yrs) were enrolled. QFT-Plus and TSPOT were concurrently conducted. Lymphocyte subsets (CD4 T-cell and CD8 T-cell) were also measured. The positivity rates of QFT-Plus and TSPOT were 9.7% and 4.5%, respectively, with the difference being significant (P < 0.01). The positivity rates in TB1 and TB2 were 9.1% and 7.1%, respectively; the difference was not significant (P = 0.18). Patients with CD4 T-cell ≥650/μL and CD8 T-cell ≥400/μL had significantly higher positivity rates in both QFT-Plus and TSPOT in comparison with other groups (P < 0.01 and P < 0.05, respectively). QFT-plus demonstrated a higher positivity rate than TSPOT. However, there was little additional effect for detecting LTBI by TB2. Lymphocyte subsets were strongly associated with immune response in both QFT-Plus and TSPOT. LTBI should not be ruled out even with a negative IGRA result in patients with CD4 T-cell <650/μL or CD8 T-cell <400/μL.