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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]

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]

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]

Objective: Estimate the prevalence of allergic, neurodevelopmental, and autoimmune diagnoses in children born to anti-Ro antibody positive mothers., Methods: A cohort study of children born to anti-Ro antibody positive mothers followed in the Neonatal Lupus Erythematosus clinic (NLE) at SickKids Hospital. Participants ≥ 1 year of age were invited to complete a health status questionnaire. Prevalence of allergic, neurodevelopmental, and autoimmune disease diagnoses were compared between from the NLE cohort and the non-NLE population-based CHILD Cohort Study. Descriptive statistics were used for demographics, NLE manifestations and outcomes. Fisher's exact tests compared the prevalence of diagnoses between subgroups. We tested the association between allergies and neurodevelopmental conditions and NLE with logistic regression models. A P-value of <0.006 was considered significant., Results: We included 321 participants with anti-Ro antibody positive mothers. Median age at survey completion: 6 years, 51% female, 50% (n=162) NLE. No significant difference in any disease prevalence between children with and without NLE manifestations (p = 0.57) nor between children born to mothers with and without a rheumatic disease (p = 0.11). Disease prevalence was similar between the NLE and CHILD cohorts, allergic disease 30% vs 22%, p= 0.25, neurodevelopmental conditions 5% vs 2%, p=0.45, autoimmune disease 4% vs 2%, p=0.68., Conclusions: In a large, multiethnic cohort of infants born to anti-Ro antibody positive mothers, there was no significant difference in the prevalence of allergic, neurodevelopmental, or autoimmune diseases between children with and without NLE, nor between those born to anti-Ro antibody positive mothers and a population-based, non-NLE cohort., (This article is protected by copyright. All rights reserved.)

Objective: To assess changes in juvenile idiopathic arthritis (JIA) treatments and outcomes in Canada, comparing 2005-2010 and 2017-2021 inception cohorts., Methods: Patients enrolled within three months of diagnosis in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) and the Canadian Alliance of Pediatric Rheumatology Investigators Registry (CAPRI) cohorts were included. Cumulative incidences of drug starts and outcome attainment within 70 weeks of diagnosis were compared with Kaplan-Meier survival analysis and multivariable Cox regression., Results: The 2005-2010 and 2017-2021 cohorts included 1128 and 721 patients, respectively. JIA category distribution and baseline clinical juvenile idiopathic arthritis disease activity (cJADAS10) scores at enrolment were comparable. By 70 weeks, 6% of patients (95% CI 5, 7) in the 2005-2010 and 26% (23, 30) in the 2017-2021 cohort had started a biologic DMARD (bDMARD), and 43% (40, 47) and 60% (56, 64) had started a conventional DMARD (cDMARD), respectively. Outcome attainment was 64% (61, 67) and 83% (80, 86) for inactive disease (Wallace criteria), 69% (66, 72) and 84% (81, 87) for minimally active disease (cJADAS10 criteria), 57% (54, 61) and 63% (59, 68) for pain control (<1/10), and 52% (47, 56) and 54% (48, 60) for good health-related quality of life (≥9/10)., Conclusion: Although baseline disease characteristics were comparable in the 2005-2010 and 2017-2021 cohorts, cDMARD and bDMARD use increased with a concurrent increase in minimally active and inactive disease. Improvements in parent and patient-reported outcomes were smaller than improvements in disease activity., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)