Exploring immunomodulation by endocrine changes in Lady Windermere syndrome

Abstract

Lung disease due to nontuberculous mycobacteria (NTM) occurs with disproportionate frequency in postmenopausal women with a unique phenotype and without clinically apparent predisposing factors. Dubbed 'Lady Windermere syndrome', the phenotype includes low body mass index (BMI), tall stature and higher than normal prevalence of scoliosis, pectus excavatum and mitral valve prolapse. Although the pathomechanism for susceptibility to NTM lung disease in these patients remains uncertain, it is likely to be multi-factorial. A role for the immunomodulatory consequences of oestrogen deficiency and altered adipokine production has been postulated. Altered levels of adipokines and dehydroepiandrosterone have been demonstrated in patients with NTM lung disease. Case reports of NTM lung disease in patients with hypopituitarism support the possibility that altered endocrine function influences disease susceptibility. This paper catalogues the evidence for immunomodulatory consequences of predicted endocrine changes in Lady Windermere syndrome, with emphasis on the immune response to NTM. Collectively, the data warrant further exploration of an endocrine link to disease susceptibility in Lady Windermere syndrome.

Impact of body mass index on development of nontuberculous mycobacterial pulmonary disease

“…Furthermore, elevation of adiponectin decreases Toll-like receptor (TLR) mediated IFNγ secretion in natural killer cells [30]. Given these observations, adipokine dysregulation in malnourished individuals could be a biological mechanism that contributes to increased risk of NTM-PD [31].…”

The Rise of Non-Tuberculosis Mycobacterial Lung Disease

“…A fourth disease cohort include elderly white postmenopausal females who present classically with NTM infection of the middle or lingular lobe of the lung. Described as "Lady Windermere syndrome" these patients often have a distinct physical phenotype of slender build, pectus excavatum or scoliosis and mitral valve prolapse, though notably they have no known immune dysfunction (16,19,28). Recently identified genetic defects that could contribute to susceptibility in these "Lady Windemere" patients include cystic fibrosis transmembrane conductance regulator gene (CFTR) related mutations, ciliary function, and other connective tissue related genetic defects as well as the DNA damage response protein TTK defects (22,(29)(30)(31).…”

Lady Windermere syndrome: Reality or myth?

“…Rarefaction and distortion of the lung parenchyma might be contributed by the pulsating heart resulting in disruption in muco-ciliary clearance. Holt et al [11] proposed immunomodulatory hypothesis for pulmonary MAC in patients with no underlying lung disease. According to their study altered level of adipokines, reduced estrogen, leptin, and ehydroepiandrosterone inhibit macrophage activation and MAC killing.…”