Finding 1: In collaboration with James Thaventhiran at Cambridge and Kaan Boztug in Austria, we identified two patients with recessive loss of function mutations in interleukin 6 receptor (IL6R) leading to absent Il-6 receptor signaling, severe atopic dermatitis, bacterial skin and lung infections, elevated immunoglobulin E (IgE) and markedly abnormal inflammatory responses. The findings were important for several reasons. First, they contextualized the role for IL-6 signaling in diseases of high IgE and infection, such as STAT3DN, gp130 deficiency and ZNF341 deficiency; they showed that IL6R is the likely binding partner for gp130 that is required to prevent elevated IgE. The second reason is that it demonstrates the potential consequences of IL-6R blockade, as is now commonly in use, highlighting the differences between inborn IL6R deletion and blockade later in life. The fact that most treated adults do not develop allergy (but can develop infection) suggests that IL6R signaling is necessary only early in life to prevent IgE elevation and severe dermatitis. The results were published in the Journal of Experimental Medicine. Finding 2: In collaboration with multiple groups throughout the world, we showed the experience of treated patients with STAT1 or STAT3GOF mutations with JAK inhibitors. We found that these inhibitors can be effective in the pathway specific treatment of these disorders, but that they tend to be more effective in combination with IL-6R blockade (mentioned in finding 1) and when initiated earlier in the disease course. The results were published in the Journal of Allergy and Clinical Immunology.
| Valent, Peter; Akin, Cem; Bonadonna, Patrizia et al. (2018) Mast cell activation syndrome: Importance of consensus criteria and call for research. J Allergy Clin Immunol 142:1008-1010 |
| Oh, Kyu-Seon; Gottschalk, Rachel A; Lounsbury, Nicolas W et al. (2018) Dual Roles for Ikaros in Regulation of Macrophage Chromatin State and Inflammatory Gene Expression. J Immunol 201:757-771 |
| Natarajan, Mukil; Hsu, Amy P; Weinreich, Michael A et al. (2018) Aspergillosis, eosinophilic esophagitis, and allergic rhinitis in signal transducer and activator of transcription 3 haploinsufficiency. J Allergy Clin Immunol 142:993-997.e3 |
| Lyons, Jonathan J; Milner, Joshua D (2018) Primary atopic disorders. J Exp Med 215:1009-1022 |
| Sabato, Vito; Chovanec, Jack; Faber, Margaretha et al. (2018) First Identification of an Inherited TPSAB1 Quintuplication in a Patient with Clonal Mast Cell Disease. J Clin Immunol 38:457-459 |
| Lyons, Jonathan J; Stotz, Stephanie C; Chovanec, Jack et al. (2018) A common haplotype containing functional CACNA1H variants is frequently coinherited with increased TPSAB1 copy number. Genet Med 20:503-512 |
| Milner, Joshua D (2018) TCR Signaling Abnormalities in Human Th2-Associated Atopic Disease. Front Immunol 9:719 |
| Schussler, Edith; Yang, Amy; Lyons, Jonathan J et al. (2018) Persistent tryptase elevation in a patient with Gaucher disease. J Allergy Clin Immunol Pract 6:697-699 |
| Ma, Chi A; Stinson, Jeffrey R; Zhang, Yuan et al. (2017) Germline hypomorphic CARD11 mutations in severe atopic disease. Nat Genet 49:1192-1201 |
| Carlson, Ryan J; Bond, Michelle R; Hutchins, Shermaine et al. (2017) Detection of phosphoglucomutase-3 deficiency by lectin-based flow cytometry. J Allergy Clin Immunol 140:291-294.e4 |
Showing the most recent 10 out of 54 publications
