Objective
To externally validate the Systemic Lupus International Collaborating Clinics Frailty Index (SLICC‐FI) in a prevalent systemic lupus erythematosus (SLE) cohort and to assess the ability of ...the SLICC‐FI to predict organ damage accrual among individuals with longstanding SLE.
Methods
This was a secondary analysis of data from the Study of Lupus Vascular and Bone Long‐Term Endpoints (SOLVABLE) cohort, which consists of adult women from the Chicago Lupus Database who met the 1997 revised American College of Rheumatology (ACR) classification criteria for SLE. There were 185 patients with SLE enrolled, of whom 149 patients were included in a 5‐year follow‐up analysis. The SLICC‐FI and SLICC/ACR Damage Index (SDI) scores were calculated at baseline and 5‐year follow‐up. Unadjusted and adjusted logistic regression models estimated the association of baseline SLICC‐FI scores (per 0.05 increase) with damage accrual at 5‐year follow‐up.
Results
At enrollment the mean ± SD age of the 149 patients was 43.30 ± 10.15 years, the mean ± SD disease duration was 11.93 ± 8.46 years, and the mean ± SD SDI score was 1.64 ± 1.83. At baseline, the mean ± SD SLICC‐FI score was 0.18 ± 0.08, and 36% of participants were categorized as frail (SLICC‐FI score >0.21). In a model adjusted for age, race, and disease duration, each 0.05‐unit increase in the baseline SLICC‐FI score was associated with 28% higher odds of subsequent damage accrual (odds ratio 1.28, 95% confidence interval 1.01–1.63).
Conclusion
In a prevalent cohort of women with established SLE, higher baseline SLICC‐FI scores were associated with a higher risk of subsequent damage accrual at 5‐year follow‐up.
Objective
To define candidate criteria within multiphase development of systemic lupus erythematosus (SLE) classification criteria, jointly supported by the American College of Rheumatology and the ...European League Against Rheumatism. Prior steps included item generation and reduction by Delphi exercise, further narrowed to 21 items in a nominal group technique exercise. Our objectives were to apply an evidence‐based approach to the 21 candidate criteria, and to develop hierarchical organization of criteria within domains.
Methods
A literature review identified the sensitivity and specificity of the 21 candidate criteria. Data on the performance of antinuclear antibody (ANA) as an entry criterion and operating characteristics of the candidate criteria in early SLE patients were evaluated. Candidate criteria were hierarchically organized into clinical and immunologic domains, and definitions were refined in an iterative process.
Results
Based on the data, consensus was reached to use a positive ANA of ≥1:80 titer (HEp‐2 cells immunofluorescence) as an entry criterion and to have 7 clinical and 3 immunologic domains, with hierarchical organization of criteria within domains. Definitions of the candidate criteria were specified.
Conclusion
Using a data‐driven process, consensus was reached on new, refined criteria definitions and organization based on operating characteristics. This work will be followed by a multicriteria decision analysis exercise to weight criteria and to identify a threshold score for classification on a continuous probability scale.
Objective
Social determinants of health (SDoH) likely contribute to outcome disparities in lupus nephritis (LN). Understanding the overall burden and contribution of each domain could guide future ...health equity–focused interventions to improve outcomes and reduce disparities in LN. Objectives of this meta‐analysis were to 1) determine the association of overall SDoH and specific SDoH domains on LN outcomes and 2) develop a framework for the multidimensional impact of SDoH on LN outcomes.
Methods
We performed a comprehensive search of studies measuring associations between SDoH and LN outcomes. We examined pooled odds of poor LN outcomes including death, end‐stage kidney disease, or cardiovascular disease in patients with and without adverse SDoH. Additionally, we calculated the pooled odds ratios of outcomes by four SDoH domains: individual (eg, insurance), health care (eg, fragmented care), community (eg, neighborhood socioeconomic status), and health behaviors (eg, smoking).
Results
Among 531 screened studies, 31 meeting inclusion criteria and 13 with raw data were included in meta‐analysis. Pooled odds of poor outcomes were 1.47‐fold higher in patients with any adverse SDoH. Patients with adverse SDoH in individual and health care domains had 1.64‐fold and 1.77‐fold higher odds of poor outcomes. We found a multiplicative impact of having two or more adverse SDoH on LN outcomes. Black patients with public insurance and fragmented care had 12‐fold higher odds of poor LN outcomes.
Conclusion
Adverse SDoH is associated with poor LN outcomes. Having two or more adverse SDoH, specifically in different SDoH domains, had a multiplicative impact leading to worse LN outcomes, widening disparities.
Objective
To evaluate the frequency of cell‐bound complement activation products (CB‐CAPs) as a marker of complement activation in patients with suspected systemic lupus erythematosus (SLE) and the ...usefulness of this biomarker as a predictor of the evolution of probable SLE into SLE as classified by the American College of Rheumatology (ACR) criteria.
Methods
Patients in whom SLE was suspected by lupus experts and who fulfilled 3 ACR classification criteria for SLE (probable SLE) were enrolled, along with patients with established SLE as classified by both the ACR and the Systemic Lupus International Collaborating Clinics (SLICC) criteria, patients with primary Sjögren's syndrome (SS), and patients with other rheumatic diseases. Individual CB‐CAPs were measured by flow cytometry, and positivity rates were compared to those of commonly assessed biomarkers, including serum complement proteins (C3 and C4) and autoantibodies. The frequency of a positive multianalyte assay panel (MAP), which includes CB‐CAPs, was also evaluated. Probable SLE cases were followed up prospectively.
Results
The 92 patients with probable SLE were diagnosed more recently than the 53 patients with established SLE, and their use of antirheumatic medications was lower. At the enrollment visit, more patients with probable SLE were positive for CB‐CAPs (28%) or MAP (40%) than had low complement levels (9%) (P = 0.0001 for each). In probable SLE, MAP scores of >0.8 at enrollment predicted fulfillment of a fourth ACR criterion within 18 months (hazard ratio 3.11, P < 0.01).
Conclusion
Complement activation occurs in some patients with probable SLE and can be detected with higher frequency by evaluating CB‐CAPs and MAP than by assessing traditional serum complement protein levels. A MAP score above 0.8 predicts transition to classifiable SLE according to ACR criteria.
Objective
A project aimed at developing new classification criteria for systemic lupus erythematosus (SLE) is based on weighted criteria that include both laboratory and clinical items. Combinations ...of certain symptoms may occur commonly in SLE, which provides an argument against independently counting these items. The current study was undertaken to evaluate the interrelationship between candidate criteria items in the International Early SLE cohort and in the Euro‐Lupus cohort.
Methods
The International Early SLE cohort included 389 patients, who were diagnosed within 3 years prior to the study. Data on the ACR’s 1997 update of the SLE revised criteria, the Systemic Lupus International Collaborating Clinics 2012 criteria, and on 30 additional items were collected. To evaluate the interrelationship of the criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations in the same organ system. The correlations identified in the International Early SLE cohort were validated in the Euro‐Lupus cohort.
Results
A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti‐Sm and anti–double‐stranded DNA and anti–RNA polymerase, anti‐Ro and anti‐La, and antiphospholipid antibodies), and these results were validated in the Euro‐Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation.
Conclusion
Some of the candidate SLE criteria cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important to consider for the structure of new SLE classification criteria.
Objective
Adipose tissues secrete adipokines, peptides with potent effects modulating fibrosis, inflammation, and vascular homeostasis. Dysregulated adipose tissue biology and adipokine balance have ...recently been implicated in systemic sclerosis (SSc). This study was undertaken to determine whether altered circulating adipokine levels correlate with SSc disease subsets or clinical manifestations.
Methods
Multiplex assays were used to measure circulating adipokine levels in 198 patients with SSc and 33 healthy controls. Data were evaluated for correlations between serum adipokine levels and demographic and clinical features, including pulmonary arterial hypertension (PAH). To assess the relevance of adipsin, an adipokine involved in complement pathway activation, in SSc, we analyzed publicly available genetic and transcriptomic data.
Results
Levels of adiponectin and adipsin differed significantly between controls and patients. Adipsin was significantly elevated in patients with limited cutaneous SSc (odds ratio OR 28.3 95% confidence interval (95% CI) 7.0–113.8; P < 0.0001), and its levels were associated with serum autoantibody status, pulmonary function and cardiovascular parameters, and PAH (OR 3.3 95% CI 1.3–8.7; P = 0.02). Elevated adipsin was more strongly associated with PAH than B‐type natriuretic peptide was. Moreover, in SSc patients, adipsin gene single‐nucleotide polymorphisms were associated with PAH. Transcriptome data set analysis demonstrated elevated adipsin expression in patients with SSc‐related PAH.
Conclusion
We identify adipsin as a novel adipose tissue–derived marker of SSc‐related PAH. Circulating adipsin levels might serve as predictive biomarkers in SSc. Mechanistically, adipsin might represent a pathogenic link between adipocyte dysfunction and complement pathway activation and play an important role in the pathogenesis of SSc‐related PAH.
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