ArticleArthritis & rheumatology (Hoboken, N.J.)2022
Excess Serum Interleukin-18 Distinguishes Patients With Pathogenic Mutations in PSTPIP1.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 34 citations in OpenAlex.
- Human Inborn Errors of Immunity in Pyoderma Gangrenosum: A Systematic Review.American journal of clinical dermatology · 2024Pooled it
- Advances in targeting IL-1 family cytokines for the treatment of inflammatory diseases.Nature reviews. Rheumatology · 2026Review
- Free IL-18 in NLRC4-associated autoinflammatory disease without macrophage activation syndrome.Rheumatology (Oxford, England) · 2026Article
- Article
- New discoveries in the genetics and genomics of systemic juvenile idiopathic arthritis.Expert review of clinical immunology · 2024Review
- Interrupting an IFN-γ-dependent feedback loop in the syndrome of pyogenic arthritis with pyoderma gangrenosum and acne.Annals of the rheumatic diseases · 2024Article
- Genetic mutations in pyoderma gangrenosum, hidradenitis suppurativa, and associated autoinflammatory syndromes: Insights into pathogenic mechanisms and shared pathways.The Journal of dermatology · 2024Review
- The 4Pediatric rheumatology online journal · 2024Article
- Biological and clinical roles of IL-18 in inflammatory diseases.Nature reviews. Rheumatology · 2024Review
- Autoinflammatory Contributors to Cytokine Storm.Advances in experimental medicine and biology · 2024Review
- Recent Insights in Pyrin Inflammasome Activation: Identifying Potential Novel Therapeutic Approaches in Pyrin-Associated Autoinflammatory Syndromes.Journal of clinical immunology · 2023Review
- Type 1 Interferon-Stimulated Gene Expression and Disease Activity in Pediatric Rheumatic Diseases: No Composite Scores Needed?ACR open rheumatology · 2023Article
- IL-18 in Autoinflammatory Diseases: Focus on Adult Onset Still Disease and Macrophages Activation Syndrome.International journal of molecular sciences · 2023Review
- Biologics and JAK inhibitors for the treatment of monogenic systemic autoinflammatory diseases in children.The Journal of allergy and clinical immunology · 2023Review
- IL-1 and autoinflammatory disease: biology, pathogenesis and therapeutic targeting.Nature reviews. Rheumatology · 2022Review
- Interleukin-18 Binding Protein in Immune Regulation and Autoimmune Diseases.Biomedicines · 2022Review
- Strong inflammatory signatures in the neutrophils of PAMI syndrome.Frontiers in immunology · 2022Article
- Pathogenic roles and diagnostic utility of interleukin-18 in autoinflammatory diseases.Frontiers in immunology · 2022Review
- Immune-mediated inflammatory diseases with chronic excess of serum interleukin-18.Frontiers in immunology · 2022Review
- Clinical and Genetic Findings of the First Report of PAPA Syndrome in Brazil.Case reports in immunology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
objectiveDominantly inherited PSTPIP1 mutations cause a spectrum of autoinflammatory manifestations epitomized by PAPA syndrome (pyogenic sterile arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome.). The connections between PSTPIP1 and PAPA syndrome are poorly understood, although evidence suggests involvement of pyrin inflammasome activation. Interleukin-18 (IL-18) is an inflammasome-activated cytokine associated with susceptibility to macrophage activation syndrome (MAS). This study was undertaken to investigate an association of IL-18 with PAPA syndrome.
methodsClinical and genetic data and serum samples were obtained from patients referred to institutions due to symptoms indicative of PAPA syndrome. Serum IL-18, IL-18 binding protein (IL-18BP), and CXCL9 levels were assessed by bead-based assay, and free IL-18 levels were assessed by enzyme-linked immunosorbent assay.
resultsThe symptoms of PSTPIP1-positive patients with PAPA syndrome overlapped with those of mutation-negative patients with PAPA-like conditions, but mutation-positive patients had earlier onset and a greater proportion had a history of arthritis. We found uniform elevation of total serum IL-18 in treated PAPA syndrome patients at levels nearly as high as those seen in NLRC4-associated autoinflammation with infantile enterocolitis patients, and well above levels found in most familial Mediterranean fever patients. Serum IL-18 elevation in PAPA syndrome patients persisted despite fluctuations in disease activity. Levels of the soluble IL-18 antagonist IL-18BP were modestly elevated, and PAPA syndrome patients had detectable free IL-18. PAPA syndrome was rarely associated with elevation of CXCL9, an indicator of interferon-γ activity, but no PAPA syndrome patients had a history of MAS.
conclusionPAPA syndrome is a refractory and often disabling monogenic autoinflammatory disease associated with chronic and unopposed elevation of serum IL-18 levels but not with risk of MAS. These findings affect our understanding of the diseases in which IL-18 is overproduced and suggest a link between pyrin inflammasome activation, IL-18, and autoinflammation, without susceptibility to MAS.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.