Anti-KIF20B autoantibodies are associated with cranial neuropathy in systemic lupus erythematosus.

BACKGROUND: Cranial neuropathies (CN) are a rare neuropsychiatric SLE (NPSLE) manifestation. Previous studies reported that antibodies to the kinesin family member 20B (KIF20B) (anti-KIF20B) protein were associated with idiopathic ataxia and CN. We assessed anti-KIF20B as a potential biomarker for NPSLE in an international SLE inception cohort. METHODS: Individuals fulfilling the revised 1997 American College of Rheumatology (ACR) SLE classification criteria were enrolled from 31 centres from 1999 to 2011 and followed annually in the Systemic Lupus Erythematosus International Collaborating Clinics inception cohort. Anti-KIF20B testing was performed on baseline (within 15 months of diagnosis or first annual visit) samples using an addressable laser bead immunoassay. Logistic regression (penalised maximum likelihood and adjusting for confounding variables) examined the association between anti-KIF20B and NPSLE manifestations (1999 ACR case definitions), including CN, occurring over the first 5 years of follow-up. RESULTS: Of the 1827 enrolled cohort members, baseline serum and 5 years of follow-up data were available on 795 patients who were included in this study: 29.8% were anti-KIF20B-positive, 88.7% female, and 52.1% White. The frequency of anti-KIF20B positivity differed only for those with CN (n=10) versus without CN (n=785) (70.0% vs 29.3%; OR 5.2, 95% CI 1.4, 18.5). Compared with patients without CN, patients with CN were more likely to fulfil the ACR haematological (90.0% vs 66.1%; difference 23.9%, 95% CI 5.0%, 42.8%) and ANA (100% vs 95.7%; difference 4.3%, 95% CI 2.9%, 5.8%) criteria. In the multivariate analysis adjusting for age at baseline, female, White race and ethnicity, and ACR haematological and ANA criteria, anti-KIF20B positivity remained associated with CN (OR 5.2, 95% CI 1.4, 19.1). CONCLUSION: Anti-KIF20B is a potential biomarker for SLE-related CN. Further studies are needed to examine how autoantibodies against KIF20B, which is variably expressed in a variety of neurological cells, contribute to disease pathogenesis.

Systemic lupus in the era of machine learning medicine.

Artificial intelligence and machine learning applications are emerging as transformative technologies in medicine. With greater access to a diverse range of big datasets, researchers are turning to these powerful techniques for data analysis. Machine learning can reveal patterns and interactions between variables in large and complex datasets more accurately and efficiently than traditional statistical methods. Machine learning approaches open new possibilities for studying SLE, a multifactorial, highly heterogeneous and complex disease. Here, we discuss how machine learning methods are rapidly being integrated into the field of SLE research. Recent reports have focused on building prediction models and/or identifying novel biomarkers using both supervised and unsupervised techniques for understanding disease pathogenesis, early diagnosis and prognosis of disease. In this review, we will provide an overview of machine learning techniques to discuss current gaps, challenges and opportunities for SLE studies. External validation of most prediction models is still needed before clinical adoption. Utilisation of deep learning models, access to alternative sources of health data and increased awareness of the ethics, governance and regulations surrounding the use of artificial intelligence in medicine will help propel this exciting field forward.

Anti-SMN autoantibodies in mixed connective tissue disease are associated with a severe systemic sclerosis phenotype.

OBJECTIVES: The survival of motor neuron (SMN) complex has an essential role in the assembly of small nuclear ribonucleoproteins (RNP). Recent reports have described autoantibodies (aAbs) to the SMN complex as novel biomarkers in anti-U1RNP+ myositis patients. The aim of this study was to compare phenotypic features of anti-U1RNP+ mixed connective tissue disease (MCTD) patients with and without anti-SMN aAbs. METHODS: A retrospective MCTD cohort was studied. Addressable laser bead immunoassay was used to detect specific anti-SMN aAbs with <300 mean fluorescence intensity (MFI) as normal reference range, 300-999 MFI as low-titre and ≥1000 MFI as high-titre positivity. Comparison of clinical features between anti-SMN+ and anti-SMN- subgroups used two-tailed Fisher's exact test, and logistic regression analyses. RESULTS: Sixty-six patients were included. Median age at MCTD diagnosis was 40.6 years, and duration of follow-up was 12 years. Based on the highest available titre, 39 (59%) were anti-SMN+: 10 (26%) had low titre and 29 (74%) had high titre. Anti-SMN+ patients had a higher frequency of fingertip pitting scars (anti-SMN+ 23% vs anti-SMN- 4%, p=0.04), lower gastrointestinal (GI) involvement (26% vs 4%, p=0.04), and myocarditis (16% vs 0%, p=0.04). The combined outcome of pitting scars and/or lower GI involvement and/or myositis and/or myocarditis was highest among high-titre anti-SMN+ patients: adjusted OR 7.79 (2.33 to 30.45, p=0.002). CONCLUSIONS: Anti-SMN aAbs were present in 59% of our MCTD cohort. Their presence, especially at high-titres, was associated with a severe systemic sclerosis (scleroderma) phenotype including myositis, myocarditis and lower GI involvement.

Identification of novel clusters of co-expressing cytokines in a diagnostic cytokine multiplex test.

Introduction: Cytokines are mediators of the immune system that are essential for the maintenance, development and resolution of immune responses. Beneficial immune responses depend on complex, interdependent networks of signaling and regulatory events in which individual cytokines influence the production and release of others. Since disruptions in these signaling networks are associated with a wide spectrum of diseases, cytokines have gained considerable interest as diagnostic, prognostic and precision therapy-relevant biomarkers. However, currently individual cytokines testing has limited value because the wider immune response context is often overlooked. The aim of this study was to identify specific cytokine signaling patterns associated with different diseases. Methods: Unbiased clustering analyses were performed on a clinical cytokine multiplex test using a cohort of human plasma specimens drawn from individuals with known or suspected diseases for which cytokine profiling was considered clinically indicated by the attending physician. Results and discussion: Seven clusters of co-expressing cytokines were identified, representing common patterns of immune activation. Common expression profiles of the cytokine clusters and preliminary associations of these profiles with specific diseases or disease categories were also identified. These findings increase our understanding of the immune environments underlying the clinical presentations of patients of inflammatory, autoimmune and neoplastic diseases, which could then improve diagnoses and the identification of evidence-based treatment targets.

Over-the-counter fish oil supplementation and pro-resolving and pro-inflammatory lipid mediators in rheumatoid arthritis.

OBJECTIVE: Little is known about the effects of over-the-counter fish oil (FO) supplements on circulating omega-3 polyunsaturated fatty acid (n-3 PUFA)-derived specialized pro-resolving mediators (SPMs), nor about whether having a chronic inflammatory disease such as rheumatoid arthritis (RA) influences SPM levels. We investigated associations between over-the-counter n-3 PUFA FO supplementation and circulating SPMs among patients with vs. without RA. METHODS: We studied 104 participants: 26 with RA taking FO matched by age and sex to 26 with RA not taking FO, 26 without RA taking FO, and 26 without RA not taking FO. Targeted-liquid chromatography-tandem mass spectroscopy was performed on patient plasma to identify and quantify 27 lipid mediators (including eicosanoids and SPMs). We performed t-tests and then multivariable linear regression analyses to assess whether having RA or taking FO supplements was associated with circulating lipid mediator concentrations, adjusting for age, race, sex, smoking, body mass index, and current medication use (statins, prednisone and immunomodulators among RA cases only). We tested for interactions between FO supplementation and RA status. We also conducted Spearman's correlations between EPA, DHA, and ARA and their downstream metabolites. RESULTS: Among patients who were taking FO compared to those who were not, in multivariable- adjusted analyses, SPM substrates EPA and DHA were both elevated as were several of their pro-resolving bioactive products, including 15- and 18-HEPE from EPA, and 14- and 17-HDHA from DHA, which are substrates for specific SPMs. While E-series and D-series resolvins were present and identified, we did not find statistical elevations of other SPMs. Results were similar among patients with RA and patients without RA, taking vs. not taking FO supplementation (no formal statistical interaction observed). There was a strong positive correlation between EPA and DHA and their immediate downstream SPM precursors (18-HEPE and15-HEPE from EPA; 17-HDHA and 14-HDHA from DHA) among all patients. CONCLUSION: Patients taking FO supplements, regardless of RA status, not only had higher blood levels of EPA and DHA, but also of their enzymatic products 18-HEPE (E-series resolvin precursors), 15-HEPE and 17-HDHA (D-series resolvin and protectin precursors). Patients with RA, an inflammatory autoimmune disease, may be able to augment some SPM precursor reserves, similarly to matched controls without RA, by taking oral FO supplements.

Association of Healthy Lifestyle Behaviors and the Risk of Developing Rheumatoid Arthritis Among Women.

OBJECTIVE: To investigate whether a healthy lifestyle, defined by a healthy lifestyle index score (HLIS), was associated with rheumatoid arthritis (RA) risk, overall and with seropositive/seronegative subtypes. METHODS: We analyzed female nurses in the Nurses' Health Study (NHS, 1986-2016) and NHSII (1991-2017). Lifestyle and medical information were collected on biennial questionnaires. Medical records confirmed incident RA and serostatus. The HLIS index includes 5 modifiable components: smoking, alcohol consumption, body mass index, physical activity, and diet. Cox regression, adjusted for confounders, modeled associations between HLIS and incident RA. The population attributable risk estimated the proportion of incident RA preventable if participants adopted ≥4 healthy lifestyle factors. RESULTS: A total of 1,219 incident RA cases (776 seropositive, 443 seronegative) developed in 4,467,751 person-years. Higher (healthier) HLIS was associated with lower overall RA risk (hazard ratio [HR] 0.86 [95% confidence interval (95% CI) 0.82-0.90]), seropositive RA risk (HR 0.85 [95% CI 0.80-0.91]), and seronegative RA risk (HR 0.87 [95% 0.80-0.94]). Women with 5 healthy lifestyle factors had the lowest risk (HR 0.42 [95% CI 0.22-0.80]). The population attributable risk for adhering to ≥4 lifestyle factors was 34% for RA. CONCLUSION: In this prospective cohort, healthier lifestyle was associated with a lower RA risk. A substantial proportion of RA may be preventable by a healthy lifestyle.

Assessing the Utility of the Montreal Cognitive Assessment in Screening for Cognitive Impairment in Patients With Systemic Lupus Erythematosus.

OBJECTIVE: Screening for cognitive impairment (CI) in systemic lupus erythematosus (SLE) relies on the American College of Rheumatology (ACR) neuropsychological battery (NB). By studying the concurrent criterion validity, our goal was to assess the Montreal Cognitive Assessment (MoCA) as a screening tool for CI compared to the ACR-NB and to evaluate the added value of the MoCA to the Automated Neuropsychological Assessment Metrics (ANAM). METHODS: A total of 285 adult SLE patients were administered the ACR-NB, MoCA, and ANAM. For the ACR-NB, patients were classified as having CI if there was a Z score of ≤-1.5 in ≥2 domains. The area under the curve (AUC) and sensitivities/specificities were determined. A discriminant function analysis was applied to assess the ability of the MoCA to differentiate between CI, undetermined CI, and non-CI patients. RESULTS: CI was not accurately identified by the MoCA compared to the ACR-NB (AUC of 0.66). Sensitivity and specificity were poor at 50% and 69%, respectively, for the cutoff of 26, and 80% and 45%, respectively, for the cutoff of 28. The MoCA had a low ability to identify CI status. The addition of the MoCA to the ANAM led to improvement on the AUC by only 2.5%. CONCLUSION: The MoCA does not have adequate concurrent criterion validity to accurately identify CI in patients with SLE. The low specificity of the MoCA may lead to overdiagnosis and concern among patients. Adding the MoCA to the ANAM does not substantially improve the accuracy of the ANAM. These results do not support using the MoCA as a screening tool for CI in patients with SLE.

Association of mycophenolate and azathioprine use with cognitive function in systemic lupus.

OBJECTIVES: Cognitive dysfunction (CD) is a common manifestation of SLE that can have detrimental consequences for those affected. To date, no treatments have been approved for SLE-CD. This study aims to assess the association of azathioprine (AZA) and mycophenolate (MMF) use with SLE-CD, given that these medications have demonstrated neuroprotective qualities in prior studies. METHODS: Consecutive adult SLE patients presenting to a single healthcare center were considered for participation. The ACR neuropsychological battery for SLE was administered to consenting patients at 0, 6 and 12 months. Scores were compared with age- and sex-matched controls. Primary outcome was CD, defined as a z-score ≤-1.5 in two or more cognitive domains. Mixed-effects logistic regression models were constructed to estimate the odds of CD with respect to AZA and MMF use. RESULTS: A total of 300 participants representing 676 patient visits completed the study; 114 (38%) met criteria for CD at baseline. The cumulative AZA dose (g/kg) was associated with reduced odds of CD [odds ratio (OR) 0.76 (95% CI 0.58, 0.98), P = 0.04]. Years of AZA treatment was also associated with reduced odds of CD [OR 0.72 (95% CI 0.54, 0.97), P = 0.03]. MMF use was not associated with CD. CONCLUSION: AZA use was associated with significantly lower odds of SLE-CD, while MMF use was not. Additional studies are warranted to further investigate the relationship of AZA and SLE-CD.

Systemic lupus erythematosus phenotypes formed from machine learning with a specific focus on cognitive impairment.

OBJECTIVE: To phenotype SLE based on symptom burden (disease damage, system involvement and patient reported outcomes), with a specific focus on objective and subjective cognitive function. METHODS: SLE patients ages 18-65 years underwent objective cognitive assessment using the ACR Neuropsychological Battery (ACR-NB) and data were collected on demographic and clinical variables, disease burden/activity, health-related quality of life (HRQoL), depression, anxiety, fatigue and perceived cognitive deficits. Similarity network fusion (SNF) was used to identify patient subtypes. Differences between the subtypes were evaluated using Kruskal-Wallis and χ2 tests. RESULTS: Of the 238 patients, 90% were female, with a mean age of 41 years (s.d. 12) and a disease duration of 14 years (s.d. 10) at the study visit. The SNF analysis defined two subtypes (A and B) with distinct patterns in objective and subjective cognitive function, disease burden/damage, HRQoL, anxiety and depression. Subtype A performed worst on all significantly different tests of objective cognitive function (P < 0.03) compared with subtype B. Subtype A also had greater levels of subjective cognitive function (P < 0.001), disease burden/damage (P < 0.04), HRQoL (P < 0.001) and psychiatric measures (P < 0.001) compared with subtype B. CONCLUSION: This study demonstrates the complexity of cognitive impairment (CI) in SLE and that individual, multifactorial phenotypes exist. Those with greater disease burden, from SLE-specific factors or other factors associated with chronic conditions, report poorer cognitive functioning and perform worse on objective cognitive measures. By exploring different ways of phenotyping SLE we may better define CI in SLE. Ultimately this will aid our understanding of personalized CI trajectories and identification of appropriate treatments.

Anti-Valosin-Containing Protein (VCP/p97) Autoantibodies in Inclusion Body Myositis and Other Inflammatory Myopathies.

OBJECTIVE: The rationale for this study was based on reports that valosin-containing protein (VCP) mutations are found in hereditary inclusion body myositis (IBM) and VCP was detected in rimmed vacuoles of sporadic IBM (sIBM) muscle biopsies. Autoantibodies to VCP have not been reported in sIBM or other inflammatory myopathies (IIMs). The aim of this study was to determine the frequency and clinical significance of anti-VCP antibodies in sIBM and other IIMs. METHODS: Sera were collected from 73 patients with sIBM and 383 comparators or controls, including patients with IIM (n = 69), those with juvenile dermatomyositis (JDM) (n = 67), those with juvenile idiopathic arthritis (JIA) (n = 47), those with primary biliary cholangitis (PBC) (n = 105), controls that were age matched to patients with sIBM (similarly aged controls [SACs]) (n = 63), and healthy controls (HCs) (n = 32). Immunoglobulin G antibodies to VCP were detected by addressable laser bead immunoassay using a full-length recombinant human protein. RESULTS: Among patients with sIBM, 26.0% (19/73) were positive for anti-VCP. The frequency in disease controls was 15.0% (48/320). Among SACs, the frequency was 1.6% (1/63), and in HCs 0% (0/32). Frequencies were 17.5% (11/63) for IIM, 25.7% (27/105) for PBC, 3.0% (2/67) for JDM, and 17.0% (8/47) for JIA. The sensitivity, specificity, positive predictive value, and negative predictive value of anti-VCP for sIBM were 26.0%, 87.2%, 28.4%, and 85.9%, respectively. Of patients with sIBM, 15.1% (11/73) were positive for both anti-VCP and anti-cytosolic 5'-nucleotidase 1A (NT5c1A). Eleven percent of patients (8/73) were positive for anti-VCP, but negative for anti-NT5c1A. CONCLUSION: Anti-VCP has low sensitivity and moderate specificity for sIBM but may help fill the seronegative gap in sIBM. Further studies are needed to determine whether anti-VCP is a biomarker for a clinical phenotype that may have clinical value.

Association of Sleep Deprivation and the Risk of Developing Systemic Lupus Erythematosus Among Women.

OBJECTIVE: Sleep deprivation has been associated with risk of autoimmune diseases. Using the Nurses' Health Study (NHS) (1986-2016) and NHSII (1989-2017) cohorts, we aimed in the present study to investigate whether sleep deprivation was associated with risk of developing systemic lupus erythematosus (SLE). METHODS: Average sleep duration in a 24-hour period was reported in the NHS (1986-2014) and NHSII (1989-2009). Lifestyle, exposure, and medical information was collected on biennial questionnaires. Adjusted Cox regression analyses modeled associations between cumulative average sleep duration (categorical variables) and incident SLE. Interactions between sleep duration and shiftwork, bodily pain (using the Short Form 36 [SF-36] questionnaire), and depression were examined. RESULTS: We included 186,072 women with 187 incident SLE cases during 4,246,094 person-years of follow-up. Chronic low sleep duration (≤5 hours/night versus reference >7-8 hours) was associated with increased SLE risk (adjusted hazard ratio [HRadj ] 2.47 [95% confidence interval (95% CI) 1.29, 4.75]), which persisted after the analysis was lagged (4 years; HRadj 3.14 [95% CI 1.57, 6.29]) and adjusted for shiftwork, bodily pain, and depression (HRadj 2.13 [95% CI 1.11, 4.10]). We detected additive interactions between low sleep duration and high bodily pain (SF-36 score <75) with an attributable proportion (AP) of 64% (95% CI 40%, 87%) and an HR for SLE of 2.97 (95% CI 1.86, 4.75) for those with both risk factors compared to those with neither. Similarly, there was an interaction between low sleep duration and depression, with an AP of 68% (95% CI 49%, 88%) and an HR for SLE of 2.82 (95% CI 1.64, 4.85). CONCLUSION: Chronic low sleep duration was associated with higher SLE risk, with stronger effects among those with bodily pain and depression, highlighting the potential role of adequate sleep in disease prevention.

Risk prediction models for incident systemic lupus erythematosus among women in the Nurses' health study cohorts using genetics, family history, and lifestyle and environmental factors.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a severe multisystem autoimmune disease that predominantly affects women. Its etiology is complex and multifactorial, with several known genetic and environmental risk factors, but accurate risk prediction models are still lacking. We developed SLE risk prediction models, incorporating known genetic, lifestyle and environmental risk factors, and family history. METHODS: We performed a nested case-control study within the Nurses' Health Study cohorts (NHS). NHS began in 1976 and enrolled 121,700 registered female nurses ages 30-55 from 11 U.S. states; NHSII began in 1989 and enrolled 116,430 registered female nurses ages 25-42 from 14 U.S. states. Participants were asked about lifestyle, reproductive and environmental exposures, as well as medical information, on biennial questionnaires. Incident SLE cases were self-reported and validated by medical record review (Updated 1997 American College of Rheumatology classification criteria). Those with banked blood samples for genotyping (∼25% of each cohort), were selected and matched by age (± 4 years) and race/ethnicity to women who had donated a blood sample but did not develop SLE. Lifestyle and reproductive variables, including smoking, alcohol use, body mass index, sleep, socioeconomic status, U.S. region, menarche age, oral contraceptive use, menopausal status/postmenopausal hormone use, and family history of SLE or rheumatoid arthritis (RA) were assessed through the questionnaire prior to SLE diagnosis questionnaire cycle (or matched index date). Genome-wide genotyping results were used to calculate a SLE weighted genetic risk score (wGRS) using 86 published single nucleotide polymorphisms (SNPs) and 10 classical HLA alleles associated with SLE. We compared four sequential multivariable logistic regression models of SLE risk prediction, each calculating the area under the receiver operating characteristic curve (AUC): 1) SLE wGRS, 2) SLE/RA family history, 3) lifestyle, environmental and reproductive factors and 4) combining model 1-3 factors. Models were internally validated using a bootstrapped estimate of optimism of the AUC. We also examined similar sequential models to predict anti-dsDNA positive SLE risk. RESULTS: We identified and matched 138 women who developed incident SLE to 1136 women who did not. Models 1-4 yielded AUCs 0.63 (95%CI 0.58-0.68), 0.64 (95%CI 0.59-0.68), 0.71(95% CI 0.66-0.75), and 0.76 (95% CI 0.72-0.81). Model 4 based on genetics, family history and eight lifestyle and environmental factors had best discrimination, with an optimism-corrected AUC 0.75. AUCs for similar models predicting anti-dsDNA positive SLE risk, were 0.60, 0.63, 0.81 and 0.82, with optimism corrected AUC of 0.79 for model 4. CONCLUSION: A final model including SLE weighted genetic risk score, family history and eight lifestyle and environmental SLE risk factors accurately classified future SLE risk with optimism corrected AUC of 0.75. To our knowledge, this is the first SLE prediction model based on known risk factors. It might be feasibly employed in at-risk populations as genetic data are increasingly available and the risk factors easily assessed. The NHS cohorts include few non-White women and mean age at incident SLE was early 50s, calling for further research in younger and more diverse cohorts.

Serum S100A8/A9 and MMP-9 levels are elevated in systemic lupus erythematosus patients with cognitive impairment.

Objective: Cognitive impairment (CI) is one of the most common manifestations of Neuropsychiatric Systemic Lupus Erythematosus (NPSLE). Despite its frequency, we have a limited understanding of the underlying immune mechanisms, resulting in a lack of pathways to target. This study aims to bridge this gap by investigating differences in serum analyte levels in SLE patients based on their cognitive performance, independently from the attribution to SLE, and exploring the potential for various serum analytes to differentiate between SLE patients with and without CI. Methods: Two hundred ninety individuals aged 18-65 years who met the 2019-EULAR/ACR classification criteria for SLE were included. Cognitive function was measured utilizing the adapted ACR-Neuropsychological Battery (ACR-NB). CI was defined as a z-score of ≤-1.5 in two or more domains. The serum levels of nine analytes were measured using ELISA. The data were randomly partitioned into a training (70%) and a test (30%) sets. Differences in the analyte levels between patients with and without CI were determined; and their ability to discriminate CI from non-CI was evaluated. Results: Of 290 patients, 40% (n=116) had CI. Serum levels of S100A8/A9 and MMP-9, were significantly higher in patients with CI (p=0.006 and p=0.036, respectively). For most domains of the ACR-NB, patients with CI had higher S100A8/A9 serum levels than those without. Similarly, S100A8/A9 had a negative relationship with multiple CI tests and the highest AUC (0.74, 95%CI: 0.66-0.88) to differentiate between patients with and without CI. Conclusion: In this large cohort of well-characterized SLE patients, serum S100A8/A9 and MMP-9 were elevated in patients with CI. S100A8/A9 had the greatest discriminatory ability in differentiating between patients with and without CI.

Health information use by patients with systemic lupus erythematosus (SLE) pre and during the COVID-19 pandemic.

OBJECTIVE: We conducted an international survey of patients with SLE to assess their access, preference and trust in various health information sources pre-COVID-19 and during the COVID-19 pandemic. METHODS: Patients with SLE were recruited from 18 observational cohorts, and patients self-reporting SLE were recruited through five advocacy organisations. Respondents completed an online survey from June 2020 to December 2021 regarding the sources of health information they accessed in the 12 months preceding (pre-11 March 2020) and during (post-11 March 2020) the pandemic. Multivariable logistic regressions assessed factors associated with accessing news and social media post-11 March 2020, and self-reporting negative impacts from health information accessed through these sources. RESULTS: Surveys were completed by 2111 respondents; 92.8% were female, 76.6% had postsecondary education, mean (SD) age was 48.8 (14.0) years. Lupus specialists and family physicians were the most preferred sources pre-11 March 2020 and post-11 March 2020, yet were accessed less frequently (specialists: 78.5% pre vs 70.2% post, difference -8.3%, 95% CI -10.2% to -6.5%; family physicians: 57.1% pre vs 50.0% post, difference -7.1%, 95% CI -9.2% to -5.0%), while news (53.2% pre vs 62.1% post, difference 8.9%, 95% CI 6.7% to 11.0%) and social media (38.2% pre vs 40.6% post, difference 2.4%, 95% CI 0.7% to 4.2%) were accessed more frequently post-11 March 2020 vs pre-11 March 2020. 17.2% of respondents reported negative impacts from information accessed through news/social media. Those outside Canada, older respondents or with postsecondary education were more likely to access news media. Those in Asia, Latin America or younger respondents were more likely to access social media. Those in Asia, older respondents, males or with postsecondary education in Canada, Asia or the USA were less likely to be negatively impacted. CONCLUSIONS: Physicians, the most preferred and trusted sources, were accessed less frequently, while news and social media, less trusted sources, were accessed more frequently post-11 March 2020 vs pre-11 March 2020. Increasing accessibility to physicians, in person and virtually, may help reduce the consequences of accessing misinformation/disinformation.

Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis.

OBJECTIVES: To determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis. METHODS: Adult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration. RESULTS: Fourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis. CONCLUSIONS: Baseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.

Development of an interdisciplinary early rheumatoid arthritis care pathway.

BACKGROUND: To develop an interdisciplinary care pathway for early rheumatoid arthritis (RA) including referral triage, diagnosis, and management. METHODS: Our process was a four-phase approach. In Phase 1, an anonymous survey was electronically distributed to division rheumatologists. This provided data to a small interprofessional working group of rheumatology team members who drafted an initial care pathway informed by evidence-based practice in Phase 2. In Phase 3, an education day was held with approximately 40 physicians (rheumatologists and rheumatology residents), members of our interprofessional team, and two clinic managers to review the proposed care elements through presentations and small group discussions. The care pathway was revised for content and implementation considerations based on feedback received. Implementation of the care pathway and development of strategies for evaluation is ongoing across multiple practice sites (Phase 4). RESULTS: Our care pathway promotes an approach to patient-centered early RA care using an interdisciplinary approach. Care pathway elements include triage processes, critical diagnostics, pre-treatment screening and vaccinations, and uptake of suggested RA pharmacologic treatment using shared decision-making strategies. Pathway implementation has been facilitated by nursing protocols and evaluation includes continuous monitoring of key indicators. CONCLUSION: The 'Calgary Early RA Care Pathway' emphasizes a patient-centered and interdisciplinary approach to early RA identification and treatment. Implementation and evaluation of this care pathway is ongoing to support, highest quality care for patients.

Understanding the Concept of Pre-Clinical Autoimmunity: Prediction and Prevention of Systemic Lupus Erythematosus: Identifying Risk Factors and Developing Strategies Against Disease Development.

There is growing evidence that preceding the diagnosis or classification of systemic lupus erythematosus (SLE), patients undergo a preclinical phase of disease where markers of inflammation and autoimmunity are already present. Not surprisingly then, even though SLE management has improved over the years, many patients will already have irreversible disease-related organ damage by time they have been diagnosed with SLE. By gaining a greater understanding of the pathogenesis of preclinical SLE, we can potentially identify patients earlier in the disease course who are at-risk of transitioning to full-blown SLE and implement preventative strategies. In this review, we discuss the current state of knowledge of SLE preclinical pathogenesis and propose a screening and preventative strategy that involves the use of promising biomarkers of early disease, modification of lifestyle and environmental risk factors, and initiation of preventative therapies, as examined in other autoimmune diseases such as rheumatoid arthritis and type 1 diabetes.

Prevalence and titres of antinuclear antibodies in juvenile idiopathic arthritis: A systematic review and meta-analysis.

BACKGROUND: Antinuclear antibodies (ANA) detected in juvenile idiopathic arthritis (JIA) sera are considered to be a biomarker for JIA-related uveitis. There is an unclear consensus on the screening dilutions of ANA as detected by the HEp-2 indirect immunofluorescence assay (IFA) that should be used when predicting the risk of uveitis in JIA. The primary aim of this systematic review and meta-analysis was to summarize the evidence regarding ANA prevalence and performance in JIA and JIA-associated uveitis. METHODS: A search of five databases identified 1766 abstracts, using the search terms juvenile idiopathic arthritis; pediatric; sensitivity or diagnostic; and ANA. Studies that met inclusion/exclusion criteria were analyzed for the proportion of JIA patients with a positive ANA. Forest plots and pooled estimates were generated for the proportion of JIA patients and those with uveitis who were positive for ANA stratified by screening dilution. Study heterogeneity was also assessed. RESULTS: Twenty-eight studies met inclusion criteria yielding 6250 unique patients; 5902 had JIA and 348 were healthy controls or were known to have other autoimmune diseases. The most reported IFA serum screening dilution was ≥1:80, representing 41.9% of patients and this screening dilution had the highest proportion of JIA ANA positivity (41.0%; 95% CI 25.0%-57.0%). ANA screening for JIA uveitis had a sensitivity and specificity of ANA at ≥1:40 of 75% (95% CI 46%-100%) and 66% (95% CI 39%-93%), respectively. There was significant study heterogeneity across both JIA subtypes and ANA titres. CONCLUSIONS: Although there was a large variation of ANA IFA screening dilutions used for investigation of JIA, the most common dilution was 1:80. The current literature has several important deficiencies that are identified in this review requiring additional studies to inform the ANA screening dilutions of clinical value in JIA and JIA-associated uveitis.