Beyond the visual analog scale: results from a multimodal pain assessment pilot study in first-degree relatives of patients with rheumatoid arthritis.
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ABSTRACT:
SUBMITTER: McDougall C
PROVIDER: S-EPMC9746659 | biostudies-literature | 2022 Dec
REPOSITORIES: biostudies-literature
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Beyond the visual analog scale: results from a multimodal pain assessment pilot study in first-degree relatives of patients with rheumatoid arthritis.
McDougall Cairistin C Wiens Dana D Smolik Irene I Lee Yvonne C YC El-Gabalawy Hani S HS O'Neil Liam J LJ
ACR open rheumatology 20221018 12
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Project description:ObjectivesThere is increasing interest in prediction and prevention of RA. It is important to understand the views of those at risk to inform the development of effective approaches. First-degree relatives (FDRs) of RA patients are at increased risk of RA. This study assessed predictors of their interest in predictive testing for RA.MethodsQuestionnaires were completed by RA patients (provided with their questionnaire by a healthcare professional) and their FDRs (provided with their questionnaire by their RA proband). FDR surveys assessed interest in taking a predictive test, demographic variables, perceived RA risk, attitudes about predictive testing, autonomy preferences, illness perceptions, avoidance coping and health anxiety. Patient surveys included demographic variables, disease impact, RA duration and treatment. Ordinal logistic regression examined the association between FDRs' characteristics and their interest in predictive testing. Generalized estimating equations assessed associations between patient characteristics and FDRs' interest in predictive testing.ResultsThree hundred and ninety-six FDRs responded. Paired data from the RA proband were available for 292. The proportion of FDRs interested in predictive testing was 91.3%. Information-seeking preferences, beliefs that predictive testing can increase empowerment over health and positive attitudes about risk knowledge were associated with increased interest. Beliefs that predictive testing could cause psychological harm predicted lower interest. Patient characteristics of the proband were not associated with FDRs' interest.ConclusionsFDRs' interest in predictive testing for RA was high, and factors associated with interest were identified. These findings will inform the development of predictive strategies and informational resources for those at risk.
| S-EPMC9348622 | biostudies-literature
Project description:Background: Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. Methods: We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ≥ 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the ‘high risk autoantibody profile (HRP)’ as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines/chemokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. Results: In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1b in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p=0.04) and a 26% lower IL-1b (p=0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p=0.0006, p=0.006, p=0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations. Conclusions: Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity may occur systemically, rather than at the joint, which may provide insight into the systemic effects of RA-related autoantibodies and inflammation in the absence of clinically apparent RA.
2018-07-01 | GSE114043 | GEO
Project description:ObjectivePhysical activity (PA) in preclinical rheumatoid arthritis (RA) is associated with lower RA risk and disease severity. As joint signs and symptoms of inflammatory arthritis serve as a barrier to PA in RA, it is important to consider whether they affect PA in the time prior to RA. Therefore, we investigated whether joint swelling, stiffness or pain were associated with PA in first-degree relatives (FDRs) of patients with RA, a population at higher risk for future RA.DesignProspective study design.SettingWe recruited FDRs of patients with RA from academic centres, Veterans' hospitals and rheumatology clinics or through responses to advertising from six sites across the USA.ParticipantsWe evaluated associations of joint stiffness, joint swelling and joint pain with PA time in 268 FDRs with ≥2 visits over an average 1.2 years. Clinicians confirmed joint swelling. Participants self-reported joint stiffness and/or pain.Primary outcome measuresPA during a typical 24-hour day was quantified via questionnaire, weighted to reflect metabolic expenditure, where 24 hours was the minimum PA time. Linear mixed models evaluated associations between symptoms and change in PA over time, adjusting for age, sex, race, body mass index, smoking and RA-related autoantibodies.ResultsAverage weighted PA time was 37±7 hours. In the cross-sectional analysis, PA time was 1.3±0.9 hours higher in FDRs reporting joint pain (p=0.15); and 0.8±1.6 and 0.4±1 hours lower in FDRs with joint swelling (p=0.60) and stiffness (p=0.69), respectively. Longitudinally, adjusting for baseline PA time, baseline symptoms were not significantly associated with changes in PA time. However, on average over time, joint stiffness and pain were associated with lower PA time (pinteraction=0.0002, pinteraction=0.002), and joint swelling was associated with higher PA time (pinteraction <0.0001).ConclusionBaseline symptoms did not predict future PA time, but on average over time, joint symptoms influenced PA time.
| S-EPMC8442039 | biostudies-literature
Project description: Not available
| S-EPMC10913638 | biostudies-literature
Project description:We present the rationale, design features, and protocol of the Personalized Risk Estimator for Rheumatoid Arthritis (PRE-RA) Family Study (ClinicalTrials.gov NCT02046005). The PRE-RA Family Study is an NIH-funded prospective, randomized controlled trial designed to compare the willingness to change behaviors in first-degree relatives of rheumatoid arthritis (RA) patients without RA after exposure to RA risk educational programs. Consented subjects are randomized to receive education concerning their personalized RA risk based on demographics, RA-associated behaviors, genetics, and biomarkers or to receive standard RA information. Four behavioral factors associated with RA risk were identified from prior studies for inclusion in the risk estimate: cigarette smoking, excess body weight, poor oral health, and low fish intake. Personalized RA risk information is presented through an online tool that collects data on an individual's specific age, gender, family history, and risk-related behaviors; presents genetic and biomarker results; displays relative and absolute risk of RA; and provides personalized feedback and education. The trial outcomes will be changes in willingness to alter behaviors from baseline to 6 weeks, 6 months, and 12 months in the three intervention groups. The design and the execution of this trial that targets a special population at risk for RA, while incorporating varied risk factors into a single risk tool, offer distinct challenges. We provide the theoretical rationale for the PRE-RA Family Study and highlight particular design features of this trial that utilize personalized risk education as an intervention.
| S-EPMC4175164 | biostudies-literature
Project description:BACKGROUND:Extra-articular manifestations of rheumatoid arthritis (RA), potentially due to systemic inflammation, include cardiovascular disease and sarcopenic obesity. Adiponectin, an adipose-derived cytokine, has been implicated in inflammatory processes in RA, but little is known regarding its association with inflammation in a pre-clinical period. Therefore, we investigated whether adiponectin was associated with inflammatory markers in individuals at risk for RA, and whether RA-related autoimmunity modifies these associations. METHODS:We analyzed samples from 144 first-degree relatives (FDRs) of RA probands, of whom 23 were positive for anti-cyclic citrullinated peptide antibody and/or ≥ 2 rheumatoid factor isotypes (IgM, IgG or IgA). We called this phenotype the 'high risk autoantibody profile (HRP)' as it has been shown in prior work to be >96% specific for future RA. We measured adiponectin, cytokines, and high-sensitivity C-reactive protein (hsCRP). Using linear mixed effects models, we evaluated interaction between HRP positivity and adiponectin on inflammatory markers, adjusting for age, sex, ethnicity, body mass index, pack-years smoking, and use of cholesterol-lowering medications. RESULTS:In everyone, adiponectin concentration was inversely associated with hsCRP and IL-1β in adjusted models, where a 1% higher adiponectin was associated with a 26% lower hsCRP (p = 0.04) and a 26% lower IL-1β (p = 0.04). Significant interactions between HRP and adiponectin for associations with GM-CSF, IL-6, and IL-9 were detected in fully adjusted models (p = 0.0006, p = 0.006, p = 0.01, respectively). In HRP positive FDRs but not HRP negative FDRs, a 1% higher adiponectin was associated with 97% higher GM-CSF, 73% higher IL-6, and 54% higher IL-9 concentrations. CONCLUSIONS:Adiponectin associates with inflammatory markers, and these associations differ in individuals with a high-risk autoantibody profile compared with those without. The interaction between adiponectin and autoimmunity warrants further investigation into the potential systemic effects of RA-related autoantibodies and adiponectin on inflammation in the absence of clinically apparent RA.
| S-EPMC6016921 | biostudies-literature
Project description:BackgroundDespite immune cell dysregulation being an important event preceding the onset of rheumatoid arthritis (RA), the phenotype of T and B cells in preclinical RA is less understood. The aim of this study was to characterize T and B cell populations in RA patients and their autoantibody (aAb) negative and positive first-degree relatives (FDR).MethodsCryopreserved peripheral blood mononuclear cells (PBMCs) collected at scheduled visits from aAb-(n=25), and aAb+ FDR (n=10) and RA patients (n=13) were thawed and stained using optimized antibody cocktails as per a specific 13-color T or B cell panel. Immunophenotyping was performed using a Cytoflex LX (Beckman-Coulter) flow cytometer and FlowJo software was used for analyzing the frequency of immune cell populations.ResultsMulticolor flow cytometry experiments identified an increased TIGIT expression in circulating lymphocytes of aAb+ FDR and RA patients, relative to aAb- FDR (P<0.01). These TIGIT+ T cells exhibited a memory phenotype and expressed high levels of PD-1, ICOS, HLA-DR, CXCR3 and CXCR5. Moreover, increased TIGIT+ CD4 T cell frequency correlated with the frequency of PD-1+ CD4 T cells (r = 0.4705: P = 0.0043) and circulating levels of ACPA and RF. We also identified a decreased frequency of CD27+IgD- switched memory B cells in RA patients (P < 0.01), while increased frequency of TIGIT+ CD4 T cells in FDR correlated with the frequency of PD1+PTEN+ B cells (r = 0.6838, P = 0.0004) and autoantibody positivity (P = 0.01).ConclusionWe demonstrate TIGIT as a distinct CD4 T cell marker for differentiating aAb- FDR from aAb+FDR and might play a critical role in regulating T and B cell crosstalk in preclinical RA.
| S-EPMC9366176 | biostudies-literature
Project description:The aim of this study was to evaluate secretory antibodies to citrullinated proteins (ACPA) in plasma and immunoglobulin (Ig)A ACPA in saliva from patients with rheumatoid arthritis (RA) and their unaffected first-degree relatives (FDRs). Patients with RA (n = 194) and first-degree relatives unaffected by RA (n = 191) were recruited for analysis of secretory antibodies to second-generation cyclic citrullinated peptides (anti-CCP) in plasma. From a subpopulation (25 RA patients, 21 first-degree relatives and 11 controls), saliva samples were obtained for IgA anti-CCP analysis. The presence of secretory ACPA was compared between subject categories, and related to genetic and environmental risk factors. Secretory ACPA occurred in 37 (19%) plasma samples from patients with RA, but only in two (1%) of FDRs. IgA ACPA in saliva was found in three of 25 (12%) patients with RA, but not in any of the 21 FDRs (< 5%). No significant associations were seen between the presence of secretory ACPA and SE or smoking, either among RA patients or among FDRs. Despite occurring in 19% of RA plasma, secretory ACPA was rare in both saliva and plasma among FDRs, even among those positive for conventional ACPA of non-mucosal origin. Longitudinal studies are warranted to determine whether circulating secretory ACPA occurs before or in parallel with the development of clinical arthritis.
| S-EPMC6954678 | biostudies-literature
Project description:The study of complex genetics in autoimmune diseases has progressed at a tremendous pace over the last 4 years, as a direct result of the enormous gains made by genome wide association studies (GWAS). Novel genetic findings are continuously being reported alongside the rapid development of genetic technologies, sophisticated statistical analysis, and larger sample collections. It is now becoming clear that multiple genes contribute to disease risk in many complex genetic disorders including rheumatoid arthritis (RA) and that there are common genetic risk factors that underlie a spectrum of autoimmune diseases. This review details the current genetic landscape of RA, and describes what GWAS has taught us in terms of missing heritability, subsets of disease, existence of genetic heterogeneity, and shared autoimmune risk loci. Finally, this review addresses the initial challenges faced in translating the wealth of genetic findings into determining the biological mechanisms that contribute to the relationship between genotype and phenotype. Unraveling the mechanism of how genes directly influence the cause of RA will lead to a better understanding of the disease and will ultimately have a direct clinical impact, informing the development of new therapies that can be utilized in the treatment of RA.
| S-EPMC5074784 | biostudies-literature
Project description:Introduction: The aim of this study was to characterize infection events in a longitudinal cohort of first-degree relatives (FDR) of probands with rheumatoid arthritis (RA) and explore their associations with RA development. To this end, newly diagnosed RA patients (n = 283), unaffected related FDR and age-matched healthy women were ascertained from the Caucasian triple women prospective Tatarstan cohort. Methods: In this cohort initiated in 1997, 26/283 (9.2%) FDR developed RA (incidence: 9.1 cases/1,000/year). At baseline and during the follow-up, information regarding infectious events (prevalence) and their incidence and duration per year were collected from all individuals. Results: Results reveal in the unaffected FDR developing RA subgroup: (i) a higher prevalence and/or incidence at baseline of upper respiratory infections (URI), otitis, tonsillitis, herpes reactivation, and skin infections; (ii) Mycoplasma sp detection was increased during pregnancy; (iii) a peak of infections started in the 3 years preceding RA onset, and thereafter decreased following RA diagnosis and treatment initiation with disease-modifying anti-rheumatic drugs (DMARDs) when considering URI, and acute tonsillitis; (iv) herpes virus reactivation, at baseline, was associated with a higher report of morning stiffness and arthralgia while independent from rheumatoid factors and anti-citrullinated peptide (CCP)2 Ab positivity; and (v) infection events represent an independent environmental factor associated with RA development. Conclusion: In conclusion, an annual increase of respiratory tract infections was found at the pre-clinical stage of RA. This could be due to alterations in the immune system that result in susceptibility to infection, controlled by DMARDs, or that the infectious events predispose to RA.
| S-EPMC6281887 | biostudies-literature