Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis

Gohar, Faekah; McArdle, Angela; Jones, Melissa; Callan, N.; Hernández, Belinda; Kessel, Christoph; Miranda-García, María Auxiliadora; Lavrič, Miha; Holzinger, Dirk; Pretzer, Carolin; Lainka, Elke; Vastert, Sebastiaan J.; Roock, Sytze de; FitzGerald, Oliver; Foell, Dirk

doi:10.1136/annrheumdis-2019-215051

Cited by 19 publications

(11 citation statements)

References 49 publications

(53 reference statements)

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“…Similar to AoSD it is suggested, that this first autoinflammatory phase is furthermore sustained by IL-18 and IL-6 [124]. IL-18 is part of the IL-1-family and induces the expression of Interferon-γ mainly by cytotoxic lymphocytes, which robustly express the IL-18 receptor.…”

Section: Still's Disease In Children and Adults-is There A Difference?mentioning

confidence: 67%

Adult-Onset Still’s Disease: Clinical Aspects and Therapeutic Approach

Tomaras¹,

Goetzke

Kallinich

et al. 2021

JCM

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Adult-onset Still’s disease (AoSD) is a rare systemic autoinflammatory disease characterized by arthritis, spiking fever, skin rash and elevated ferritin levels. The reason behind the nomenclature of this condition is that AoSD shares certain symptoms with Still’s disease in children, currently named systemic-onset juvenile idiopathic arthritis. Immune dysregulation plays a central role in AoSD and is characterized by pathogenic involvement of both arms of the immune system. Furthermore, the past two decades have seen a large body of immunological research on cytokines, which has attributed to both a better understanding of AoSD and revolutionary advances in treatment. Additionally, recent studies have introduced a new approach by grouping patients with AoSD into only two phenotypes: one with predominantly systemic features and one with a chronic articular disease course. Diagnosis presupposes an extensive diagnostic workup to rule out infections and malignancies. The severe end of the spectrum of this disease is secondary haemophagocytic lymphohistiocytosis, better known as macrophage activation syndrome. In this review, we discuss current research conducted on the pathogenesis, diagnosis, classification, biomarkers and complications of AoSD, as well as the treatment strategy at each stage of the disease course. We also highlight the similarities and differences between AoSD and systemic-onset juvenile idiopathic arthritis. There is a considerable need for large multicentric prospective trials.

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Section: Still's Disease In Children and Adults-is There A Difference?mentioning

confidence: 67%

Adult-Onset Still’s Disease: Clinical Aspects and Therapeutic Approach

Tomaras¹,

Goetzke

Kallinich

et al. 2021

JCM

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“…Random forest analysis revealed that using this MRM assay panel, it was possible to discriminate PsA from RA with an AUC of 0.79 ( Figure 3A ). During a second verification phase, an additional 23 proteins, identified as being discriminatory in other analyses of inflammatory arthritis patients, were added to the initial MRM assay panel, giving a new total number of proteins of 173 (represented by 334 peptides) [28]. This expanded panel was used to measure protein candidates in an independent verification cohort of 95 PsA and 72 RA patients ( Table 1 ).…”

Section: Resultsmentioning

confidence: 99%

Identification and Evaluation of Serum Protein Biomarkers Which Differentiate Psoriatic from Rheumatoid Arthritis

Ardle¹,

Kwaśnik

Szenpetery³

et al. 2020

Preprint

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Objectives To identify serum protein biomarkers which might separate early inflammatory arthritis (EIA) patients with psoriatic arthritis (PsA) from those with rheumatoid arthritis (RA) to provide an accurate diagnosis and support appropriate early intervention. Methods In an initial protein discovery phase, the serum proteome of a cohort of patients with PsA and RA was interrogated using unbiased liquid chromatography mass spectrometry (LC-MS/MS) (n=64 patients), a multiplexed antibody assay (Luminex) for 48 proteins (n=64 patients) and an aptamer-based assay (SOMAscan) targeting 1,129 proteins (n=36 patients). Subsequently, analytically validated targeted multiple reaction monitoring (MRM) assays were developed to further evaluate those proteins identified as discriminatory during the discovery. During an initial verification phase, MRM assays were developed to a panel of 150 proteins (by measuring a total of 233 peptides) and used to re-evaluate the discovery cohort (n=60). During a second verification phase, the panel of proteins was expanded to include an additional 23 proteins identified in other proteomic discovery analyses of arthritis patients. The expanded panel was evaluated using a second, independent cohort of PsA and RA patients (n=167). Results Multivariate analysis of the protein discovery data revealed that it was possible to discriminate PsA from RA patients with an area under the curve (AUC) of 0.94 for nLC-MS/MS, 0.69 for Luminex based measurements; 0.73 for SOMAscan analysis. During the initial verification phase, random forest models confirmed that proteins measured by MRM could differentiate PsA and RA patients with an AUC of 0.79 and during the second phase of verification the expanded panel could segregate the two disease groups with an AUC of 0.85. Conclusion We report a serum protein biomarker panel which can separate EIA patients with PsA from those with RA. We suggest that the routine use of such a panel in EIA patients will improve clinical decision making and with continued evaluation and refinement using additional patient cohorts will support the development of a diagnostic test for patients with PsA.

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“…Für die in Neutrophilen und Monozyten exprimierten Proteine der S-100-Familie -Myeloid-related-Protein-(MRP)-8 (S100A8) und -(MRP)-14 (S100A9) -wurde vielfach gezeigt, dass sie sich zur differenzialdiagnostischen Abgrenzung zwischen der sJIA und anderen autoinflammatorischen Erkrankungen eignen. Darüber hinaus ist auch eine Verlaufsdifferenzierung der initial primär autoinflammatorisch gegenüber der später polyartikulär verlaufenden sJIA mithilfe eines molekularen Signaturpanels aus Protein S-100A8/9, A 12, IL-1, -6, -8, -18,-23, -IL1R möglich [11,[26][27][28][29][30]. Zum Monitoring der Krankheitsaktivität und zur möglichen Entwicklung eines MAS zeigte sich IL-18 als valider Parameter [31,32].…”

Section: Laborunclassified

Update – Systemische juvenile Arthritis

Hospach¹,

Horneff²

2021

Kinder- und Jugendmedizin

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ZUSAMMENFASSUNGDie systemische juvenile idiopathische Arthritis nimmt unter den Kategorien der JIA eine Sonderstellung ein, klinisch aufgrund der obligat extraartikulären, systemischen Beteiligung, aber auch aufgrund der der vital bedrohlichen Komplikationen, Makrophagenaktivierungssyndrom und Lungenbeteiligung. Untersuchungen legen ein biphasisches Krankheitsgeschehen mit konsekutiven Eigenschaften einer autoinflammatorischen mit denen einer Autoimmunerkrankung nahe. Diese Erkenntnisse führten zu Therapieoptionen wie der IL-1- und IL-6-Blockade mit Biologika und zu Therapiealgorithmen, die zwischen früher Erkrankung und später Erkrankung unterscheiden, letztlich mit dem Ziel, der Nutzung eines „windows of opportunity“ zur Erreichung des Therapieziels der Remission.

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Molecular signature characterisation of different inflammatory phenotypes of systemic juvenile idiopathic arthritis

Cited by 19 publications

References 49 publications

Adult-Onset Still’s Disease: Clinical Aspects and Therapeutic Approach

Adult-Onset Still’s Disease: Clinical Aspects and Therapeutic Approach

Identification and Evaluation of Serum Protein Biomarkers Which Differentiate Psoriatic from Rheumatoid Arthritis

Update – Systemische juvenile Arthritis

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