Evaluation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in children and adults

Cheng, Sang; Ding, Huihua; Xue, Haiyan; Cao, Lanfang

doi:10.1007/s10067-022-06293-x

Cited by 11 publications

(11 citation statements)

References 24 publications

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“…Similarly, clinical tests to diagnose SLE or to predict flares have also lagged behind other scientific advances in medicine. In the "omics" era of biomarker discovery via DNA/RNA sequencing, epigenetics, and proteomics, SLE is still largely diagnosed and treated according to clinical classification criteria, as defined by the American College of Rheumatology (ACR) and the Systemic Lupus International Collaborating Clinics (SLICC) [39,40]. Typical laboratory testing conventionally ordered in the clinic to aid in SLE diagnosis includes anti-nuclear antibodies (ANA), anti-double-stranded DNA antibodies (anti-dsDNA), and complement levels, but these tests have limited sensitivity and specificity [41][42][43].…”

Section: Discussionmentioning

confidence: 99%

Inhibition of extracellular vesicle-encapsulated miRNA produced by estrogen-mediated upregulation of cellular processing suppresses target organ inflammation in a humanized model of systemic lupus erythematosus

Young

Schwarz

Mesa

et al. 2022

Preprint

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Background/Purpose: Distinct, disease-associated intracellular miRNA (miR) expression profiles have been identified from peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematous (SLE) patients. We have previously demonstrated novel estrogenic responses in PBMCs from SLE patients and discovered that estrogen lowers the threshold of immune cell activation to a greater extent in females, including significant upregulation of toll-like receptor (TLR)7 and TLR8 expression. TLR7 and TLR8 bind viral-derived single-stranded RNA to stimulate innate inflammatory responses, but recent studies have shown that miR-21, mir-29a, and miR-29b can also bind and activate these receptors when packaged and secreted in extracellular vesicles (EVs). Objective: The objective of this study was to characterize the estrogen-mediated immunomodulatory effects of distinct EV-encapsulated miR profiles in SLE and evaluate the potential therapeutic approach of miR inhibition in a humanized mouse model. Methods: SLE patients meeting revised ACR guidelines and age/sex-matched healthy controls provided informed consent to participate in this IRB-approved study. Plasma-derived EVs were isolated by differential ultracentrifugation and quantified. PBMCs were isolated from whole blood and cultured in hormone free conditions before stimulation with 17 beta-estradiol (estrogen; E2). RNA was isolated following E2 stimulation or EV isolation and bulk RNA-sequencing (RNAseq) reads were analyzed. Additionally, PBMCs from active SLE patients were injected into immunodeficient mice to produce chimeras. Prior to transfer, the PBMCs were incubated with liposomal EVs containing complementary locked nucleic acid (LNA) antagonists to miR-21, mir-29a, and miR-29b. After three weeks, blood was collected for both immunophenotyping and cytokine analysis and tissue was harvested for histopathological examination. Results: EVs were found to be increased in the plasma of SLE patients and differentially expressed EV-derived miR profiles were detected compared to healthy controls, including miR-21, mir-29a, and miR-29b. E2 stimulation of PBMCs identified upregulated pathways involved in miR transcription/processing. Specifically, small RNA binding proteins and synthesis enzymes demonstrated significant signaling pathway association and upregulation with E2 treatment. Human immune cell subtypes were successfully recovered from whole blood of chimeric mice at similar levels with and without miR inhibition, but levels of human IL-6, IL-1 beta, IL-4, and TNF-alpha were significantly reduced by the LNA antagonists. Moreover, miR antagonists significantly reduced histopathological infiltrates in the small intestine, liver, and kidney, as demonstrated by H&E-stained tissue sections and immunohistochemistry measuring human CD3. Conclusion: These data suggest E2-mediated regulation of miR synthesis and demonstrate distinct EV-derived small RNA signatures representing SLE-associated biomarkers. Targeting upregulated EV-encapsulated miR signaling by antagonizing miRs that may bind to TLR7 and TLR8 reveals a novel therapeutic opportunity to suppress autoimmune-mediated inflammation and pathogenesis in SLE.

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Section: Discussionmentioning

confidence: 99%

Inhibition of extracellular vesicle-encapsulated miRNA produced by estrogen-mediated upregulation of cellular processing suppresses target organ inflammation in a humanized model of systemic lupus erythematosus

Young

Schwarz

Mesa

et al. 2022

Preprint

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“…Para pacientes com doença precoce, os critérios SLICC 2012 demonstraram ser mais sensíveis, da mesma forma para pacientes cuja doença Brazilian Journal of Health Review, Curitiba, v. 6, n. 1, p.1150-1164, jan./feb., 2023 ainda não está estabelecida com envolvimento de múltiplos órgãos, ou seja, cuja doença apresenta uniorganicamente os critérios ACR 1997 e SLICC foram mais sensíveis. 21 . Pacientes cuja duração da doença é inferior a 5 anos, os critérios do SLICC 2012 terão melhor desempenho na classificação de pacientes.…”

Section: Sensibilidade E Especificidade Dos Sistemas De Classificação Dounclassified

“…Embora os critérios ACR/EULAR sejam os mais atualizados, há certas considerações a serem levadas em conta ao escolher os critérios para cada paciente, assim, para jovens e crianças, é muito melhor usar os critérios SLICC. 19,21 Por exemplo, no caso de pacientes com doença precoce e uniorgânica, são sugeridos critérios SLICC. 20,22 .…”

Section: Sensibilidade E Especificidade Dos Sistemas De Classificação Dounclassified

Lúpus eritematoso sistêmico com fator antinuclear (FAN) negativo: um desafio no diagnóstico

Pacheco¹,

Pulla²,

Ortega³

et al. 2023

Braz. J. Hea. Rev.

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O lúpus eritematoso sistêmico (LES) é uma doença auto-imune que afeta 20 a 150 pessoas por 100.000 habitantes, caracterizada pela produção de auto-anticorpos, sendo os principais anticorpos envolvidos na patofisiologia desta doença os anticorpos antinucleares conhecidos como fator antinúcleo (FAN). O FAN positivo é agora considerado o critério de entrada para a classificação dos pacientes com FAN negativo, o que representa um desafio diagnóstico para aqueles com FAN negativo, uma entidade clínica descrita desde 1976 com uma prevalência de 2-20%. Apesar dos avanços nas técnicas de identificação do FAN, há vários fatores do paciente como idade, atividade da doença, uso de glicocorticóides, proteinúria, infecção e/ou sepse, que levam à negatividade de anticorpos no diagnóstico; assim como diferentes fatores técnicos ao processar o FAN por imunofluorescência indireta (IFI). Esta revisão aborda critérios de classificação do LES, técnicas de identificação do FAN, causas de negatividade e outros métodos de diagnóstico para aqueles pacientes com anticorpos antinucleares negativo e LES clínico, com o objetivo de fornecer informações aos profissionais de saúde que permitam o diagnóstico e tratamento oportuno dos pacientes com esta patologia, melhorando assim seu prognóstico e qualidade de vida.

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“…2 Hence, the American College of Rheumatology (ACR) SLE classification criteria and its revised version in the late nineties were globally applied and consequently improved our insight about the disease. 3 This improvement was evident in routine clinical practice by demonstrating several explicit skin manifestations and utilising immunological tests like complement levels (C3 &C4) and anti-B2Glycoprotein I (Anti-B2GPI) antibodies. Furthermore, mucocutaneous and several other organ involvements were better understood, warranting modifications to the classification criteria employed.…”

Section: Introductionmentioning

confidence: 99%

“…Upon assessing the three criteria, the EULAR/ACR criteria achieved the highest specificity and sensitivity of 93.4% and 96.1% as compared to 93% and 82.8% and 83.7% and 96.7% by revised ACR and SLICC criteria, respectively. 3 Furthermore, neuropsychiatric manifestations could be the presenting symptom of systemic lupus erythematosus. 7 These manifestations range from mild to severe, requiring high clinical suspicion to recognise and diagnose early.…”

Section: Introductionmentioning

confidence: 99%

Anti-Ribosomal-P Antibody Association with Neuropsychiatric Lupus in Sudanese Patients Attending Rheumatology Clinic in Omdurman Military Hospital

Taha¹,

Ibrahim²,

Hamza³

et al. 2022

OARRR

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To assess and establish the relationship between neuropsychiatric systemic lupus erythematosus (NPSLE) involvement and serological biomarkers like antiribosomal-P antibodies. Patients and Methods: This is an analytical cross-sectional hospital-based study conducted on patients attending Omdurman Military Hospital from July 2019 to December 2019. A total of 90 patients were enrolled, 30 of whom had NPSLE compared with 60 SLE patients without NPSLE. SLE diagnosis was established based on the revised SLICC criteria (presence of at least 4 criteria) for SLE classification, with neuropsychiatric manifestations defined based on the ACR nomenclature. The immunological examination results have been performed by (ELISA immune-enzymatic method, immunofluorescence, and Western immunoblotting test). SPSS v 21.0 software was utilised for data analysis. Results: NPSLE patients exhibited +ve ANA in 96.7% vs 75% in non-NPSLE (P-value = 0.008), antiribosomal-P antibodies (46.7% vs 20%; P-value = 0.0001), anti-nucleosome antibodies (26.7% vs 5%; P-value = 0.005), and anti-histones antibodies (40% vs 20%; P-value = 0.04). ANA antibodies were significantly associated with neurological manifestations as ANA antibodies were common in epilepsy (n = 9; 91%) and stroke (n = 8; 27.6%) (P-value < 0.001). Conclusion: Neuropsychiatric manifestation of systemic lupus erythematosus exhibits variable clinical manifestations. Neuropsychiatric manifestations of SLE are strongly associated with the anti-ribosomal P antibody presence and can be employed as a powerful diagnostic tool.

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Evaluation of the 2019 EULAR/ACR classification criteria for systemic lupus erythematosus in children and adults

Cited by 11 publications

References 24 publications

Inhibition of extracellular vesicle-encapsulated miRNA produced by estrogen-mediated upregulation of cellular processing suppresses target organ inflammation in a humanized model of systemic lupus erythematosus

Inhibition of extracellular vesicle-encapsulated miRNA produced by estrogen-mediated upregulation of cellular processing suppresses target organ inflammation in a humanized model of systemic lupus erythematosus

Lúpus eritematoso sistêmico com fator antinuclear (FAN) negativo: um desafio no diagnóstico

Anti-Ribosomal-P Antibody Association with Neuropsychiatric Lupus in Sudanese Patients Attending Rheumatology Clinic in Omdurman Military Hospital

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