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.

Keywords: adipokines; hormones; immune response; nontuberculous mycobacteria; oestrogen.

Figure 1

The immune response to nontuberculous mycobacteria (NTM) and predicted modulation by hormone changes. Macrophages phagocytose NTM and produce tumour necrosis factor (TNF)‐α and interleukin (IL)‐12. TNF‐α activates macrophage functions in an autocrine manner and both hormones stimulate NK cells to produce IFN‐γ. Macrophages and other antigen‐presenting cells produce IL‐12, which facilitates lymphoproliferation and drives polarisation of CD4 cells to the T helper type 1 (Th1) phenotype. Th1 and CD8 cells produce IFN‐γ, which further activates macrophages, establishing a positive feedback loop with IL‐12. Predicted modulation of these processes by hormone changes is indicated by black (inhibitory effect) and red (enhancing effect) connecting lines.