Usage Information
Citation Information: JCI Insight. 2022;7(24):e150849. https://doi.org/10.1172/jci.insight.150849.
Abstract
Primary atopic disorders are a group of inborn errors of immunity that skew the immune system toward severe allergic disease. Defining the biology underlying these extreme monogenic phenotypes reveals shared mechanisms underlying common polygenic allergic disease and identifies potential drug targets. Germline gain-of-function (GOF) variants in JAK1 are a cause of severe atopy and eosinophilia. Modeling the JAK1GOF (p.A634D) variant in both zebrafish and human induced pluripotent stem cells (iPSCs) revealed enhanced myelopoiesis. RNA-Seq of JAK1GOF human whole blood, iPSCs, and transgenic zebrafish revealed a shared core set of dysregulated genes involved in IL-4, IL-13, and IFN signaling. Immunophenotypic and transcriptomic analysis of patients carrying a JAK1GOF variant revealed marked Th cell skewing. Moreover, long-term ruxolitinib treatment of 2 children carrying the JAK1GOF (p.A634D) variant remarkably improved their growth, eosinophilia, and clinical features of allergic inflammation. This work highlights the role of JAK1 signaling in atopic immune dysregulation and the clinical impact of JAK1/2 inhibition in treating eosinophilic and allergic disease.
Authors
Catherine M. Biggs, Anna Cordeiro-Santanach, Sergey V. Prykhozhij, Adam P. Deveau, Yi Lin, Kate L. Del Bel, Felix Orben, Robert J. Ragotte, Aabida Saferali, Sara Mostafavi, Louie Dinh, Darlene Dai, Katja G. Weinacht, Kerry Dobbs, Lisa Ott de Bruin, Mehul Sharma, Kevin Tsai, John J. Priatel, Richard A. Schreiber, Jacob Rozmus, Martin C.K. Hosking, Kevin E. Shopsowitz, Margaret L. McKinnon, Suzanne Vercauteren, Michael Seear, Luigi D. Notarangelo, Francis C. Lynn, Jason N. Berman, Stuart E. Turvey
Usage data is cumulative from December 2024 through December 2025.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 981 | 414 |
| 181 | 102 | |
| Figure | 437 | 6 |
| Supplemental data | 73 | 17 |
| Citation downloads | 130 | 0 |
| Totals | 1,802 | 539 |
| Total Views | 2,341 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
