ArticleArthritis & rheumatology (Hoboken, N.J.)2021
Novel Majeed Syndrome-Causing LPIN2 Mutations Link Bone Inflammation to Inflammatory M2 Macrophages and Accelerated Osteoclastogenesis.
Article in Arthritis & rheumatology (Hoboken, N.J.), 2021. 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 13 papers, 1 of them a synthesis that pooled it.
What it found
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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
13 citing papers in PubMed, 1 synthesis or guideline pooled it, 22 citations in OpenAlex.
- Off-label use of canakinumab in pediatric rheumatology and rare diseases.Frontiers in medicine · 2022Pooled it
- Novel gain-of-function mutation in dysferlin causes vesicle trafficking defect and IL-1 mediated autoinflammation.medRxiv : the preprint server for health sciences · 2026Article
- A novelLife science alliance · 2026Article
- Association of CXCL16 in aseptic loosening following total hip arthroplasty and its effect on bone metabolism: a case-control study.Annals of medicine · 2025Article
- Lipin phosphatidic acid phosphatases: Structure, function, regulation, and disease association.Advances in biological regulation · 2025Review
- Clinical and genetic analysis of Majeed syndrome caused by LPIN2 complex heterozygous mutation and literature review.Frontiers in pediatrics · 2025Article
- Mulberry leaves supplementation alters lipid metabolism and promotes fatty acid β oxidation in growing mutton sheep.Journal of animal science · 2024Article
- Article
- Safety and efficacy of canakinumab treatment for undifferentiated autoinflammatory diseases: the data of a retrospective cohort two-centered study.Frontiers in medicine · 2023Article
- Biologic Therapies for the Management of Cutaneous Findings in Genodermatoses: A Review.American journal of clinical dermatology · 2022Review
- Chronic Nonbacterial Osteomyelitis in Children.Children (Basel, Switzerland) · 2021Review
- Deficiency of Lipin2 Results in Enhanced NF-κB Signaling and Osteoclast Formation in RAW-D Murine Macrophages.International journal of molecular sciences · 2021Article
- Majeed Syndrome: A Review of the Clinical, Genetic and Immunologic Features.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
20 authors at 7 institutions in 1 country.
Funding
Abstract
objectiveTo identify novel heterozygous LPIN2 mutations in a patient with Majeed syndrome and characterize the pathomechanisms that lead to the development of sterile osteomyelitis.
methodsTargeted genetic analysis and functional studies assessing monocyte responses, macrophage differentiation, and osteoclastogenesis were conducted to compare the pathogenesis of Majeed syndrome to interleukin-1 (IL-1)-mediated diseases including neonatal-onset multisystem inflammatory disease (NOMID) and deficiency of the IL-1 receptor antagonist (DIRA).
resultsA 4-year-old girl of mixed ethnic background presented with sterile osteomyelitis and elevated acute-phase reactants. She had a 17.8-kb deletion on the maternal LPIN2 allele and a splice site mutation, p.R517H, that variably spliced out exons 10 and 11 on the paternal LPIN2 allele. The patient achieved long-lasting remission receiving IL-1 blockade with canakinumab. Compared to controls, monocytes and monocyte-derived M1-like macrophages from the patient with Majeed syndrome and those with NOMID or DIRA had elevated caspase 1 activity and IL-1β secretion. In contrast, lipopolysaccharide-stimulated, monocyte-derived, M2-like macrophages from the patient with Majeed syndrome released higher levels of osteoclastogenic mediators (IL-8, IL-6, tumor necrosis factor, CCL2, macrophage inflammatory protein 1α/β, CXCL8, and CXCL1) compared to NOMID patients and healthy controls. Accelerated osteoclastogenesis in the patient with Majeed syndrome was associated with higher NFATc1 levels, enhanced JNK/MAPK, and reduced Src kinase activation, and partially responded to JNK inhibition and IL-1 (but not IL-6) blockade.
conclusionWe report 2 novel compound heterozygous disease-causing mutations in LPIN2 in an American patient with Majeed syndrome. LPIN2 deficiency drives differentiation of proinflammatory M2-like macrophages and enhances intrinsic osteoclastogenesis. This provides a model for the pathogenesis of sterile osteomyelitis which differentiates Majeed syndrome from other IL-1-mediated autoinflammatory diseases.
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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.