Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome

Journal article

Publication Details

Author(s): Kreins AY, Ciancanelli MJ, Okada S, Kong XF, Ramirez-Alejo N, Kilic SS, El Baghdadi J, Nonoyama S, Mahdaviani SA, Ailal F, Bousfiha A, Mansouri D, Nievas E, Ma CS, Rao G, Bernasconi A, Kuehn HS, Niemela J, Stoddard J, Deveau P, Cobat A, El Azbaoui S, Sabri A, Lim CK, Sundin M, Avery DT, Halwani R, Grant AV, Boisson B, Bogunovic D, Itan Y, Moncada-Velez M, Martinez-Barricarte R, Migaud M, Deswarte C, Alsina L, Kotlarz D, Klein C, Muller-Fleckenstein I, Fleckenstein B, Cormier-Daire V, Rose-John S, Picard C, Hammarstrom L, Puel A, Al-Muhsen S, Abel L, Chaussabel D, Rosenzweig SD, Minegishi Y, Tangye SG, Bustamante J, Casanova JL, Boisson-Dupuis S
Journal: Journal of Experimental Medicine
Publication year: 2015
Volume: 212
Journal issue: 10
Pages range: 1641-62
ISSN: 0022-1007


Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-?/?, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17(+) T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-?, IL-28/29 (IFN-?), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-?/?. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans.

FAU Authors / FAU Editors

Fleckenstein, Bernhard Prof. Dr.
Lehrstuhl für Klinische und Molekulare Virologie

External institutions with authors

Baylor Institute for Immunology Research
Christian-Albrechts-Universität zu Kiel
Hôpital Necker-Enfants malades
Hospital Garrahan
Hospital Pediátrico Alexander Fleming
Karolinska Institute
Karolinska University Hospital / Karolinska Universitetssjukhuset
King Saud University (KSU) / جامعة الملك سعود‎‎
Ludwig-Maximilians-Universität (LMU)
Military Hospital Mohammed V
National Defense Medical College / 防衛医科大学校
Rockefeller University
Shahid Beheshti University of Medical Sciences
Sidra Medical and Research Center
St Vincent's Hospital
Tokyo Medical and Dental University (TMDU) / 東京医科歯科大学
Uludag University
University Hassan II Casablanca / جامعة الحسن الثانی دارالبیضاء
University of Paris 5 - René Descartes / Université Paris V René Descartes
US National Institutes of Health (NIH)

How to cite

Kreins, A.Y., Ciancanelli, M.J., Okada, S., Kong, X.-F., Ramirez-Alejo, N., Kilic, S.S.,... Boisson-Dupuis, S. (2015). Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome. Journal of Experimental Medicine, 212(10), 1641-62.

Kreins, Alexandra Y., et al. "Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome." Journal of Experimental Medicine 212.10 (2015): 1641-62.


Last updated on 2018-05-10 at 07:26