Abstract
Autosomal recessive IL-1R-associated kinase 4 (IRAK-4) deficiency is a rare cause of recurrent pyogenic infections with limited inflammatory responses. We describe an adult female patient with severe lung disease who was phenotypically diagnosed as suffering from autosomal dominant Hyper IgE syndrome (AD HIES) because of recurrent skin infections with Staphylococcus aureus, recurrent pneumonia and elevated serum IgE levels. In contrast to findings in AD HIES patients, no abnormalities were found in the Th17 and circulating follicular helper T cell subsets. A panel-based sequencing approach led to the identification of a homozygous IRAK4 stop mutation (c.877C > T, p.Gln293*).
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Acknowledgments
This work was supported by a GOA grant from the Research Council of the Catholic University of Leuven, Belgium. HS receives research support from the Research Foundation Flanders (FWO). RS and IM are supported by a KOF mandate of the KU Leuven, Belgium.
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GF drafted the manuscript and conducted experiments. LM conducted experiments and aided in preparing the manuscript and the HIES work-up. GW conducted the TLR testing. RS, BB, HS, and LD participated in the clinical care of the patient. XB supervised the routine laboratory immunology work-up and TLR testing. AC performed the genetic analysis and established the genetic diagnosis. IM drafted and finalized the manuscript, characterized the immune deficiency and is coordinating clinical care for the patient. Each author has critically revised the final version of the manuscript and has read and approved the final manuscript.
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The authors declare that they have no conflict of interest.
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The study was performed in accordance with the 1964 Helsinki declaration and its later amendments. Informed consent was obtained for genetic analysis and report of the case. The study was approved by the Ethics Committee of UZ Leuven.
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Xavier Bossuyt, Anniek Corveleyn and Isabelle Meyts contributed equally to this work.
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Frans, G., Moens, L., Schrijvers, R. et al. PID in Disguise: Molecular Diagnosis of IRAK-4 Deficiency in an Adult Previously Misdiagnosed With Autosomal Dominant Hyper IgE Syndrome. J Clin Immunol 35, 739–744 (2015). https://doi.org/10.1007/s10875-015-0205-x
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DOI: https://doi.org/10.1007/s10875-015-0205-x