The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis
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...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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European Respiratory Society
2018
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| Online Access: | https://eprints.nottingham.ac.uk/53430/ |
| _version_ | 1848798939319369728 |
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| author | Miller, Suzanne Coveney, Claire Johnson, Janice Farmaki, Aliki-Eleni Gupta, Nishant Tobin, Martin D. Wain, Louise V. McCormack, Francis Boocock, David J. Johnson, Simon R. |
| author_facet | Miller, Suzanne Coveney, Claire Johnson, Janice Farmaki, Aliki-Eleni Gupta, Nishant Tobin, Martin D. Wain, Louise V. McCormack, Francis Boocock, David J. Johnson, Simon R. |
| author_sort | Miller, Suzanne |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T20:27:44Z |
| format | Article |
| id | nottingham-53430 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T20:27:44Z |
| publishDate | 2018 |
| publisher | European Respiratory Society |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-534302020-01-29T04:30:19Z https://eprints.nottingham.ac.uk/53430/ The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis Miller, Suzanne Coveney, Claire Johnson, Janice Farmaki, Aliki-Eleni Gupta, Nishant Tobin, Martin D. Wain, Louise V. McCormack, Francis Boocock, David J. Johnson, Simon R. 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. European Respiratory Society 2018-07-29 Article PeerReviewed application/pdf en https://eprints.nottingham.ac.uk/53430/1/ERJ%20-%20Miller%20et%20al%202018.pdf Miller, Suzanne, Coveney, Claire, Johnson, Janice, Farmaki, Aliki-Eleni, Gupta, Nishant, Tobin, Martin D., Wain, Louise V., McCormack, Francis, Boocock, David J. and Johnson, Simon R. (2018) The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis. European Respiratory Journal . ISSN 1399-3003 (In Press) |
| spellingShingle | Miller, Suzanne Coveney, Claire Johnson, Janice Farmaki, Aliki-Eleni Gupta, Nishant Tobin, Martin D. Wain, Louise V. McCormack, Francis Boocock, David J. Johnson, Simon R. The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis |
| title | The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis |
| title_full | The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis |
| title_fullStr | The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis |
| title_full_unstemmed | The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis |
| title_short | The vitamin D binding protein axis modifies disease severity in Lymphangioleiomyomatosis |
| title_sort | vitamin d binding protein axis modifies disease severity in lymphangioleiomyomatosis |
| url | https://eprints.nottingham.ac.uk/53430/ |