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The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis

Miller, Suzanne; Coveney, Clare; Johnson, Janice; Farmaki, Aliki Eleni; Gupta, Nishant; Tobin, Martin D.; Wain, Louise V.; McCormack, Francis X.; Boocock, David J.; Johnson, Simon R.


Senior Clinical Studies and Project Manager

Clare Coveney

Janice Johnson

Aliki Eleni Farmaki

Nishant Gupta

Martin D. Tobin

Louise V. Wain

Francis X. McCormack

David J. Boocock

Professor of Respiratory Medicine


Background: Lymphangioleiomyomatosis (LAM) is a rare disease of women. Decline in lung function is variable making appropriate targeting of therapy difficult. We used unbiased serum proteomics to identify markers associated with outcome in LAM.
Methods: 101 women with LAM and 22 healthy controls were recruited from the National Centre for LAM (Nottingham, UK). 152 DNA and serum samples with linked lung function and outcome data were obtained from patients in the NHLBI LAM Registry (USA). Proteomic analysis was performed on a discovery cohort of 50 LAM and 20 control sera using a SCIEX SWATH mass spectrometric workflow. Protein levels were quantitated by ELISA and SNPs in GC encoding Vitamin D Binding Protein (VTDB) genotyped.
Results: Proteomic analysis showed VTDB was 2.6 fold lower in LAM than controls. Serum VTDB was lower in progressive compared with stable LAM (p=0.001) and correlated with diffusing capacity (p=0.01). Median time to death or lung transplant was reduced by 46?months in those with CC genotypes at rs4588 and 38?months in those with non-A containing haplotypes at rs7041/4588 (p=0.014 and 0.008 respectively).
Conclusions: The VTDB axis is associated with disease severity and outcome, and GC genotype could help predict transplant free survival in LAM.


Miller, S., Coveney, C., Johnson, J., Farmaki, A. E., Gupta, N., Tobin, M. D., …Johnson, S. R. (2018). The vitamin D binding protein axis modifies disease severity in lymphangioleiomyomatosis. European Respiratory Journal, 52(5), Article 1801074.

Journal Article Type Article
Acceptance Date Jul 29, 2018
Online Publication Date Aug 9, 2018
Publication Date Nov 1, 2018
Deposit Date Nov 8, 2018
Publicly Available Date Nov 8, 2018
Journal European Respiratory Journal
Print ISSN 0903-1936
Electronic ISSN 1399-3003
Publisher European Respiratory Society
Peer Reviewed Peer Reviewed
Volume 52
Issue 5
Article Number 1801074
Keywords Pulmonary and Respiratory Medicine
Public URL
Publisher URL


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