The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome
Open accessAbstract
Inflammasomes are innate immune sensors that respond to pathogen- and damage-associated signals with caspase-1 activation, interleukin (IL)-1β and IL-18 secretion, and macrophage pyroptosis. The discovery that dominant gain-of-function mutations in NLRP3 cause the cryopyrin-associated periodic syndromes (CAPS) and trigger spontaneous inflammasome activation and IL-1β oversecretion led to successful treatment with IL-1–blocking agents. Herein we report a de novo missense mutation (c.1009A>T, encoding p.Thr337Ser) affecting the nucleotide-binding domain of the inflammasome component NLRC4 that causes early-onset recurrent fever flares and macrophage activation syndrome (MAS). Functional analyses demonstrated spontaneous inflammasome formation and production of the inflammasome-dependent cytokines IL-1β and IL-18, with the latter exceeding the levels seen in CAPS. The NLRC4 mutation caused constitutive caspase-1 cleavage in cells transduced with mutant NLRC4 and increased production of IL-18 in both patient-derived and mutant NLRC4–transduced macrophages. Thus, we describe a new monoallelic inflammasome defect that expands the monogenic autoinflammatory disease spectrum to include MAS and suggests new targets for therapy.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Kumar, P., Henikoff, S., & Ng, P. C. (2009) · Nature Protocols · doi:10.1038/nprot.2009.86 · Cited by 6,521
Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm
Biswas, S. K., & Mantovani, A. (2010) · Nature Immunology · doi:10.1038/ni.1937 · Cited by 3,840
Predicting Functional Effect of Human Missense Mutations Using PolyPhen‐2
Adzhubei, I., Jordan, D. M., & Sunyaev, S. R. (2013) · Current Protocols in Human Genetics · doi:10.1002/0471142905.hg0720s76 · Cited by 3,705
MutationTaster evaluates disease-causing potential of sequence alterations
Schwarz, J. M., Rödelsperger, C., Schuelke, M., & Seelow, D. (2010) · Nature Methods · doi:10.1038/nmeth0810-575 · Cited by 2,975
Inflammasomes in health and disease
Strowig, T., Henao-Mejia, J., Elinav, E., & Flavell, R. (2012) · Nature · doi:10.1038/nature10759 · Cited by 2,230
Use of Canakinumab in the Cryopyrin-Associated Periodic Syndrome
Lachmann, H. J., Kone-Paut, I., Kuemmerle-Deschner, J. B., Leslie, K. S., Hachulla, E., Quartier, P., Gitton, X., Widmer, A., Patel, N., & Hawkins, P. N. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0810787 · Cited by 869
Severe imbalance of IL-18/IL-18BP in patients with secondary hemophagocytic syndrome
Mazodier, K. (2005) · Blood · doi:10.1182/blood-2005-05-1980 · Cited by 290
Interleukin-18, more than a Th1 cytokine
Novick, D., Kim, S., Kaplanski, G., & Dinarello, C. A. (2013) · Seminars in Immunology · doi:10.1016/j.smim.2013.10.014 · Cited by 280
Shimizu, M., Yokoyama, T., Yamada, K., Kaneda, H., Wada, H., Wada, T., Toma, T., Ohta, K., Kasahara, Y., & Yachie, A. (2010) · Rheumatology · doi:10.1093/rheumatology/keq133 · Cited by 255
Fall, N., Barnes, M., Thornton, S., Luyrink, L., Olson, J., Ilowite, N. T., Gottlieb, B. S., Griffin, T., Sherry, D. D., Thompson, S., et al. (2007) · Arthritis & Rheumatism · doi:10.1002/art.22981 · Cited by 245
Self-citation
Cited by
Inflammasomes: mechanism of assembly, regulation and signalling
Broz, P., & Dixit, V. M. (2016) · Nature Reviews Immunology · doi:10.1038/nri.2016.58 · Cited by 3,500
Inflammasomes: mechanism of action, role in disease, and therapeutics
Guo, H., Callaway, J. B., & Ting, J. P.-Y. (2015) · Nature Medicine · doi:10.1038/nm.3893 · Cited by 3,340
Pyroptotic cell death defends against intracellular pathogens
Jorgensen, I., & Miao, E. A. (2015) · Immunological Reviews · doi:10.1111/imr.12287 · Cited by 1,021
Mutation of NLRC4 causes a syndrome of enterocolitis and autoinflammation
Romberg, N., Al Moussawi, K., Nelson-Williams, C., Stiegler, A. L., Loring, E., Choi, M., Overton, J., Meffre, E., Khokha, M. K., Huttner, A. J., et al. (2014) · Nature Genetics · doi:10.1038/ng.3066 · Cited by 517
A 360° view of the inflammasome: Mechanisms of activation, cell death, and diseases
Barnett, K. C., Li, S., Liang, K., & Ting, J. P.-Y. (2023) · Cell · doi:10.1016/j.cell.2023.04.025 · Cited by 458
Metadata
- Authors
- Canna, S. W., de Jesus, A. A., Gouni, S., Brooks, S. R., Marrero, B., Liu, Y., DiMattia, M. A., Zaal, K. J. M., Sanchez, G. A. M., Kim, H., Chapelle, D., Plass, N., Huang, Y., Villarino, A. V., Biancotto, A., Fleisher, T. A., Duncan, J. A., O'Shea, J. J., Benseler, S., Grom, A., Deng, Z., Laxer, R. M., & Goldbach-Mansky, R.
- Venue
- Nature Genetics
- Published
- 2014-09-14
- Volume
- 46
- Issue
- 10
- Pages
- 1140-1146
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W2028368428
- Cited by
- 740
- References
- 11
- FWCI
- 22.88
- Type
- journal article
- Language
- en
- Open access
- green
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. https://app.cochat.ai/papers/10.1038/ng.3089
- The paper
- Canna, S. W., de Jesus, A. A., Gouni, S., Brooks, S. R., Marrero, B., Liu, Y., DiMattia, M. A., Zaal, K. J. M., Sanchez, G. A. M., Kim, H., Chapelle, D., Plass, N., Huang, Y., Villarino, A. V., Biancotto, A., Fleisher, T. A., Duncan, J. A., O'Shea, J. J., Benseler, S., . . . Goldbach-Mansky, R. (2014). An activating NLRC4 inflammasome mutation causes autoinflammation with recurrent macrophage activation syndrome. Nature Genetics. https://doi.org/10.1038/ng.3089
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
