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Background Transplacental fetal treatment of immune-mediated fetal heart disease, including third-degree atrioventricular block (AVB III) and endocardial fibroelastosis, is controversial. Methods and Results To study the impact of routine transplacental fetal treatment, we reviewed 130 consecutive cases, including 108 with AVB III and 22 with other diagnoses (first-degree/second-degree atrioventricular block [n=10]; isolated endocardial fibroelastosis [n=9]; atrial bradycardia [n=3]). Dexamethasone was started at a median of 22.4 gestational weeks. Additional treatment for AVB III included the use of a β-agonist (n=47) and intravenous immune globulin (n=34). Fetal, neonatal, and 1-year survival rates with AVB III were 95%, 93%, and 89%, respectively. Variables present at diagnosis that were associated with perinatal death included an atrial rate

Objective: Our objective was to evaluate the development of a systemic autoimmune rheumatic disease (SARD) in undifferentiated and asymptomatic individuals with antinuclear antibodies (ANAs). We comparatively evaluated those who did and did not develop a SARD and fulfillment of classification criteria. Methods: We conducted a cohort study of undifferentiated and asymptomatic patients with ANAs who were assessed for the development of a SARD. The primary outcome was a diagnosis of a SARD over a two‐year period. We assessed fulfillment of classification criteria. Risk ratios (RRs) were used to evaluate differences among those who did and did not progress to a SARD. Results: We evaluated 207 asymptomatic ANA‐positive or undifferentiated patients, of whom 23 (11%) progressed to a SARD, whereas 187 (89%) did not progress. Progressors developed systemic lupus erythematosus (SLE) (n = 11 [48%]), Sjögren disease (n = 5 [22%]), systemic sclerosis (n = 3 [13%]), rheumatoid arthritis (n = 1 [4%]), and from ANA‐positive to undifferentiated connective tissue disease (n = 3 [13%]). Fever (RR 0.89, 95% confidence interval [CI] 0.8–0.93) and antiphospholipid antibodies (RR 0.89, 95% CI 0.87–0.93) occurred less frequently, whereas arthritis (RR 1.74, 95% CI 1.20–2.55) occurred more frequently in progressors. Progressors to SLE had arthritis (91%), whereas none developed delirium, psychosis, or nephritis. Among patients with SLE, 100% fulfilled the EULAR/American College of Rheumatology (ACR) SLE criteria (sensitivity 91.7%, specificity 100%), whereas 73% fulfilled the 1997 ACR SLE criteria (sensitivity 81.8%, specificity 98.9%). Conclusion: Most undifferentiated/asymptomatic individuals with ANA do not progress to a SARD over a two‐year period. SLE progressors appear to have mild disease in the short term. The EULAR/ACR SLE criteria have improved ability to identify those who develop SLE. [ABSTRACT FROM AUTHOR]

ObjectiveParticipants in the Atherosclerosis Prevention in Paediatric Lupus Erythematosus (APPLE) trial were randomised to placebo or atorvastatin for 36 months. The primary endpoint, reduced carotid intima medial thickness (CIMT) progression, was not met but atorvastatin-treated participants showed a trend of slower CIMT progression. Post-hoc analyses were performed to assess subgroup benefit from atorvastatin therapy.MethodsSubgroups were prespecified and defined by age (> or ≤15.5 years), systemic lupus erythematosus (SLE) duration (> or ≤24 months), pubertal status (Tanner score≥4 as post-pubertal or

Abstract Introduction The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). Methods We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. Results There were 1020 patients aged

INTRODUCTION: The aim of this study was to assess cancer incidence in childhood-onset systemic lupus erythematosus (SLE). METHODS: We ascertained cancers within SLE registries at 10 pediatric centers. Subjects were linked to cancer registries for the observational interval, spanning 1974 to 2009. The ratio of observed to expected cancers represents the standardized incidence ratio (SIR) or relative cancer risk in childhood-onset SLE, versus the general population. RESULTS: There were 1020 patients aged

Objectives Genome-wide association studies (GWAS) have identified loci associated with estimated glomerular filtration rate (eGFR). Few LN risk loci have been identified to date. We tested the association of SLE and eGFR polygenic risk scores (PRS) with repeated eGFR measures from children and adults with SLE. Methods Patients from two tertiary care lupus clinics that met ≥4 ACR and/or SLICC criteria for SLE were genotyped on the Illumina MEGA or Omni1-Quad arrays. PRSs were calculated for SLE and eGFR, using published weighted GWA-significant alleles. eGFR was calculated using the CKD-EPI and Schwartz equations. We tested the effect of eGFR- and SLE-PRSs on eGFR mean and variance, adjusting for age at diagnosis, sex, ancestry, follow-up time, and clinical event flags. Results We included 1158 SLE patients (37% biopsy-confirmed LN) with 36 733 eGFR measures over a median of 7.6 years (IQR: 3.9–15.3). LN was associated with lower within-person mean eGFR [LN: 93.8 (s. d. 26.4) vs non-LN: 101.6 (s. d. 17.7) mL/min per 1.73 m2 ; P  < 0.0001] and higher variance [LN median: 157.0 (IQR: 89.5, 268.9) vs non-LN median: 84.9 (IQR: 46.9, 138.2) (mL/min per 1.73 m2)2; P  < 0.0001]. Increasing SLE-PRSs were associated with lower mean eGFR and greater variance, while increasing eGFR-PRS was associated with increased eGFR mean and variance. Conclusion We observed significant associations between SLE and eGFR PRSs and repeated eGFR measurements, in a large cohort of children and adults with SLE. Longitudinal eGFR may serve as a powerful alternative outcome to LN categories for discovery of LN risk loci. [ABSTRACT FROM AUTHOR]

Objectives Cardiac involvement in neonatal lupus erythematosis (NLE) can present as myocarditis/endocardial fibroelastosis (EFE). It is unknown whether high-sensitivity cardiac troponin T (hs-cTnT) is useful in identifying subclinical myocardial inflammation in infants exposed prenatally to anti-Ro antibodies. This study reports hs-cTnT levels in infants exposed to anti-Ro antibodies with/without cardiac NLE and reports cardiac MRI (CMR) findings in a subset of these children. Methods The study included 45 consecutive infants exposed prenatally to anti-Ro antibodies with (n  = 7) or without (n  = 38) cardiac NLE, who were seen at the SickKids NLE Clinic between 2012 and 2014. Hs-cTnT levels were measured at least once, and those infants with values of ≥30 ng/l were offered the opportunity to undergo CMR. Descriptive statistics were performed. Results Of 38 infants without cardiac NLE, 25 had a hs-cTnT level of ≥30 ng/l (including 1 of >113 ng/l); of these, 8 underwent CMR (all without myocarditis/EFE). All 7 infants with cardiac NLE had at least one hs-cTnT level of ≥30 ng/l, but only 2/7 had a level of >113 ng/l; 4/7 infants with cardiac NLE had CMR (all without myocarditis/EFE); 6/7 infants with cardiac NLE had their steroid treatment adjusted based on the trend in their hs-cTnT levels. Conclusion Only 3/45 anti-Ro antibodies–exposed infants had hs-cTnT values outside the reference range reported in healthy infants. None of 12 infants who had CMR had subclinical myocarditis/EFE. Routine measurement of hs-cTnT in every anti-Ro antibody–exposed infant is not indicated. Further studies are needed to define the role of hs-cTnT as a biomarker for cardiac NLE. [ABSTRACT FROM AUTHOR]

Objective: Anti‐Ro antibody–positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti‐Ro antibody titers and fetal CNL. Methods: Antibody‐positive mothers referred since 2018 for fetal echocardiography at risk of CNL (group 1; n = 240) or with CNL (group 2; n = 18) were included. Maternal antibody titers were measured with a chemiluminescent immunoassay (CIA). Additional testing on diluted serum samples was used to quantify anti–Ro 60 antibody titers above the analytical measuring range (AMR) of the standard CIA (≥1,375 chemiluminescent units [CU]). Results: Among 27 total mothers with a fetal diagnosis of CNL, all displayed anti–Ro 60 antibody titers that exceeded the AMR of the CIA at least 10‐fold. Of 122 mothers in group 1 who underwent additional anti–Ro 60 antibody testing, event rates of CNL (n = 9) were 0% (0 of 45) among mothers with anti–Ro 60 antibody titers from 1,375–10,000 CU, 5% (3 of 56) among mothers with titers from 10,000–50,000 CU, but 29% (6 of 21) among mothers with titers >50,000 CU (odds ratio 13.1, P = 0.0008). Of mothers in group 2 with a primary diagnosis of CNL, 0% (0 of 18 mothers) had anti–Ro 60 antibody titers <10,000 CU, 44% (8 of 18 mothers) had titers from 10,000–50,000 CU, and 56% (10 of 18 mothers) had titers >50,000 CU. Conclusion: CNL is associated with substantially higher anti‐Ro antibody titers than are obtained using a standard CIA. Enhancing the assay measuring range allows an improved specificity of identifying pregnancies at risk of CNL. [ABSTRACT FROM AUTHOR]

Objectives Genetics plays an important role in SLE risk, as well as osteonecrosis (ON), a significant and often debilitating complication of SLE. We aimed to identify genetic risk loci for ON in people with childhood-onset (cSLE) and adult-onset (aSLE) SLE. Methods We enrolled participants from two tertiary care centres who met classification criteria for SLE. Participants had prospectively collected clinical data and were genotyped on a multiethnic array. Un-genotyped single nucleotide polymorphisms (SNPs) were imputed, and ancestry was inferred using principal components (PCs). Our outcome was symptomatic ON confirmed by imaging. We completed time-to-ON and logistic regression of ON genome-wide association studies (GWASs) with covariates for sex, age of SLE diagnosis, five PCs for ancestry, corticosteroid use and selected SLE manifestations. We conducted separate analyses for cSLE and aSLE and meta-analysed results using inverse-variance weighting. Genome-wide significance was P  < 5 × 10−8. Results The study included 940 participants with SLE, 87% female and 56% with cSLE. ON was present in 7.6% (n  = 71). Median age of SLE diagnosis was 16.9 years (interquartile range [IQR]: 13.5, 29.3), with median follow-up of 8.0 years (IQR: 4.2, 15.7). Meta-GWAS of cSLE and aSLE time-to-ON of 4 431 911 SNPs identified a significant Chr.2 SNP, rs34118383 (minor allele frequency = 0.18), intronic to WIPF1 (hazard ratio = 3.2 [95% CI: 2.2, 4.8]; P  = 1.0 × 10−8). Conclusion We identified an intronic WIPF1 variant associated with a 3.2 times increased hazard for ON (95% CI: 2.2, 4.8; P   =  1.0 × 10−8) during SLE follow-up, independent of corticosteroid exposure. The effect of the SNP on time-to-ON was similar in cSLE and aSLE. This novel discovery represents a potential ON risk locus. Our results warrant replication. [ABSTRACT FROM AUTHOR]

Systemic lupus erythematosus (SLE) is an autoimmune disease causing significant morbidity and mortality, despite important improvements in its management in the last decades. The objective of this work is to investigate the role of IFN‐γ in the pathogenesis of childhood‐onset systemic lupus erythematosus (cSLE), evaluating the crosstalk between IFN‐α and IFN‐γ and the expression of T‐bet, a transcription factor induced by IFN‐γ, in B cells of patients with cSLE. Expression levels of both IFN‐α and IFN‐γ‐induced genes were upregulated in patients with cSLE. We found increased serum levels of CXCL9 and CXCL10 in patients with cSLE. Type I IFN score decreased with initiation of immunosuppressive treatment; conversely, type II IFN score and levels of CXCL9 were not significantly affected by immunosuppressive treatment. Type II IFN score and CXCL9 were significantly higher in patients with lupus nephritis. We observed the expansion of a population of naïve B cells expressing T‐bet in a cluster of patients with cSLE. IFN‐γ, but not IFN‐α, induced the expression of T‐bet in B cells. Our data suggest that IFN‐γ is hyperactive in cSLE, especially in patients with lupus nephritis, and it is not modulated by therapy. Our data reinforce the potential of IFN‐γ as a therapeutic target in SLE. [ABSTRACT FROM AUTHOR]

Introduction Renal involvement occurs in approximately 50 % of cases of paediatric systemic lupus erythematosus (pSLE) and is associated with significant long-term morbidity and mortality [1]. The outcome of lupus [...], Background Studies of paediatric patients with membranous lupus nephritis (MLN) have yielded variable results, mostly due to the inclusion of mixed, i.e. proliferative nephritis. The aim of this study was to describe clinical and laboratory findings at the diagnosis of paediatric non-proliferative MLN, report the outcome and identify predictors of remission. Methods A single-center cohort study of consecutive children diagnosed with non-proliferative MLN was performed. Clinical and laboratory measures and treatment regimens were obtained in prospective standardized assessments. Renal outcome was measured by renal parameters and steroid requirement. Predictors for remission and time to remission were determined. Results A total of 30 children were identified with a median follow-up time 4.1 years. Of 21 patients followed for more than 2 years, 19 (90 %) achieved clinical remission, and 16 (76 %) achieved a state of maintained clinical remission on low-dose prednisone. Three patients developed proliferative nephritis on subsequent renal biopsy. Lower albumin at the time of biopsy was correlated with a lower rate of remission and longer time to remission. Conclusions Among our paediatric patient cohort the outcome of non-proliferative MLN in systemic lupus erythematosus was good. The majority of patients did not require aggressive immunosuppressive treatment to reach a stable disease state on low-dose steroid treatment. Keywords Children * Class V nephritis * Membranous glomerulonephritis * Outcome * Systemic lupus erythematosus * Treatment

The safety and efficacy of leflunomide was compared with that of methotrexate in the treatment of polyarticular juvenile rheumatoid arthritis in a multinational, randomized, controlled trial. It was concluded that in patients with polyarticular juvenile rheumatoid arthritis, methotrexate and leflunomide both resulted in high rates of clinical improvement with a slight greater rate for methotrexate.