Extract
The prevalence of pulmonary nontuberculous mycobacterial (pNTM) disease is increasing [1]. The most commonly isolated disease-causing NTMs belong to theMycobacterium aviumcomplex [1]. Susceptibility to and clinical manifestation of NTM disease are largely governed by the immune status of a person. Disseminated or extrapulmonary NTM infections are strongly associated with severe immunosuppression, such as those with frank defects in the interferon (IFN)-γ–interleukin (IL)-12 axis [2]. Isolated pNTM is strongly associated with certain underlying conditions, such as cystic fibrosis, chronic obstructive pulmonary disease and primary ciliary dyskinesia [3, 4]. However, substantial numbers of pNTM patients have no apparent risk factors, and a significant proportion of them exhibit a body morphotype characterised by lifelong slender body habitus, pectus excavatum, scoliosis and mitral valve prolapse [5, 6], also called the Lady Windermere syndrome. A modest reduction in IFN-γ production and an increase in transforming growth factor (TGF)-β levels have been described [7–10]. Fowleret al.[11] quantified ciliary beat frequency of 58 pNTM patients and 40 controls and found reduced ciliary beat frequency in the pNTM patients. Szymanskiet al.[12] performed whole-exome sequencing on patients with pNTM, their unaffected family members and a control group and concluded that pNTM is a multigenic disease, encompassing potential defects in proteins encoded by cilia genes, the cystic fibrosis transmembrane conductance regulator gene, connective tissue genes and certain immune-related genes.
Abstract
Susceptibility to NTM infections in patients with Lady Windermere syndrome is associated withMST1Rvariantshttp://ow.ly/xKgX304uhse
Acknowledgements
We thank Melanie Wattenberg and Nicole Aalders for their great assistance in the tuberculosis lab and to Bart Loeys (all at Dept of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands) for helpful discussions. We are also grateful to all the patients for participating in the study. We thank Patricia Merkel and Vijaya Knight (National Jewish Health, Denver, CO, USA) for performing the Stat1a analysis.
Footnotes
Support Statement: A. Hoischen, C. Gilissen and F. van de Veerdonk are supported by Veni grants of the Netherlands Organisation for Scientific Research (NWO). J.A. Veltman was supported by a European Research Council (ERC) starting grant (281964). M.G. Netea is supported by Vici grants from the NWO and by an ERC consolidator grant (310372). F. van de Veerdonk is supported by the Euopean Research Area-Net for Research Programmes on Rare Diseases “EURO-CMC”. Funding information for this article has been deposited withOpen Funder registry.
Conflict of interest: None declared.
- ReceivedApril 15, 2016.
- AcceptedSeptember 19, 2016.
- Copyright ©ERS 2017