Trial reportThe Journal of clinical investigation2020
Distinct interferon signatures and cytokine patterns define additional systemic autoinflammatory diseases.
Trial report in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02974595 (Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases), which is not on this map. Cited by 139 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Studies of the Natural History, Pathogenesis, and Outcome of Autoinflammatory Diseases (NOMID/CAPS, DIRA, CANDLE, SAVI, NLRC4-MAS, Still'S-like Diseases, and Other Undifferentiated Autoinflammatory Diseases)
Who cites it
139 citing papers in PubMed, 3 syntheses or guidelines pooled it, 230 citations in OpenAlex.
- The Gut-Bone Axis and Skeletal Health: Regulatory Mechanisms and Therapeutic Applications of Plant-Derived Bioactive Compounds.Biomolecules · 2026Pooled it
- The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS.Annals of the rheumatic diseases · 2022Pooled it
- The role of interleukin-18 in the diagnosis and monitoring of hemophagocytic lymphohistiocytosis/macrophage activation syndrome - a systematic review.Clinical and experimental immunology · 2021Pooled it
- Trial
- Proteasome mutations associated with CANDLE syndrome cause altered neuronal development by dysregulating polyamine synthesis.The Journal of clinical investigation · 2026Article
- Structural mechanisms of SAMD9 autoinhibition and pathogenic dysregulation.Science advances · 2026Article
- Baseline Clinical Features and Biomarker Profiles of the Childhood Arthritis and Rheumatology Research Alliance Systemic Juvenile Idiopathic Arthritis-Associated Lung Disease Cohort.Arthritis care & research · 2026Article
- Type I Interferon Signature is Associated With Lung Disease, Drug-Associated Immune Reactions, and Genetic Variation in Interferon-Linked Pathways in Still Disease.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- Examination of HLA-DRB1*15-linked Candidate Antigens in Still Disease With and Without Lung Disease and Drug-Associated Immune Reactions.The Journal of rheumatology · 2026Article
- Monoallelic PSMB8 variants cause PRAAS with immunodeficiency through impaired immunoproteasome assembly.American journal of human genetics · 2026Article
- Monogenic autoimmune and autoinflammatory disorders in adulthood: recent discoveries and implications for rheumatology practice.Rheumatology (Oxford, England) · 2026Review
- Efficacy of combined JAK1/2 inhibition and cyclosporine in paediatric-onset Still's disease with lung involvement: a case report.Pediatric rheumatology online journal · 2026Article
- BK virus nephropathy in a native kidney.Pediatric nephrology (Berlin, Germany) · 2026Article
- Serum Cytokine Profiling Differentiates Underlying Diseases in Cytokine Storm Syndrome.Arthritis & rheumatology (Hoboken, N.J.) · 2026Article
- [Interferon scores in the management of rheumatic systemic diseases].Zeitschrift fur Rheumatologie · 2026Review
- Recent variant discoveries and emerging genetic mechanisms in autoinflammatory diseases.Frontiers in immunology · 2026Review
- Immunosuppression in down syndrome regression disorder: a prospective observational cohort study.Brain communications · 2026Article
- Juvenile-onset Systemic Lupus Erythematosus: Recent Advances in Pathogenesis and Treatment.Current rheumatology reports · 2025Review
- Evolutionary characterization of antiviral SAMD9/9L across kingdoms supports ancient convergence and lineage-specific adaptations.Nature ecology & evolution · 2025Article
- Systemic Sclerosis in Kazakh Patients: A Preliminary Case-Control Immunogenetic Profiling Study.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
79 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
87 authors at 20 institutions in 17 countries.
Funding
Abstract
BACKGROUNDUndifferentiated systemic autoinflammatory diseases (USAIDs) present diagnostic and therapeutic challenges. Chronic interferon (IFN) signaling and cytokine dysregulation may identify diseases with available targeted treatments.METHODSSixty-six consecutively referred USAID patients underwent underwent screening for the presence of an interferon signature using a standardized type-I IFN-response-gene score (IRG-S), cytokine profiling, and genetic evaluation by next-generation sequencing.RESULTSThirty-six USAID patients (55%) had elevated IRG-S. Neutrophilic panniculitis (40% vs. 0%), basal ganglia calcifications (46% vs. 0%), interstitial lung disease (47% vs. 5%), and myositis (60% vs. 10%) were more prevalent in patients with elevated IRG-S. Moderate IRG-S elevation and highly elevated serum IL-18 distinguished 8 patients with pulmonary alveolar proteinosis (PAP) and recurrent macrophage activation syndrome (MAS). Among patients with panniculitis and progressive cytopenias, 2 patients were compound heterozygous for potentially novel LRBA mutations, 4 patients harbored potentially novel splice variants in IKBKG (which encodes NF-κB essential modulator [NEMO]), and 6 patients had de novo frameshift mutations in SAMD9L. Of additional 12 patients with elevated IRG-S and CANDLE-, SAVI- or Aicardi-Goutières syndrome-like (AGS-like) phenotypes, 5 patients carried mutations in either SAMHD1, TREX1, PSMB8, or PSMG2. Two patients had anti-MDA5 autoantibody-positive juvenile dermatomyositis, and 7 could not be classified. Patients with LRBA, IKBKG, and SAMD9L mutations showed a pattern of IRG elevation that suggests prominent NF-κB activation different from the canonical interferonopathies CANDLE, SAVI, and AGS.CONCLUSIONSIn patients with elevated IRG-S, we identified characteristic clinical features and 3 additional autoinflammatory diseases: IL-18-mediated PAP and recurrent MAS (IL-18PAP-MAS), NEMO deleted exon 5-autoinflammatory syndrome (NEMO-NDAS), and SAMD9L-associated autoinflammatory disease (SAMD9L-SAAD). The IRG-S expands the diagnostic armamentarium in evaluating USAIDs and points to different pathways regulating IRG expression.TRIAL REGISTRATIONClinicalTrials.gov NCT02974595.FUNDINGThe Intramural Research Program of the NIH, NIAID, NIAMS, and the Clinical Center.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.