Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis

Monique E Hinchcliff*, Chiang Ching Huang, Tammara A. Wood, J. Matthew Mahoney, Viktor Martyanov, Swati Bhattacharyya, Zenshiro Tamaki, Julia Lee, Mary Carns, Sofia Podlusky, Arlene Sirajuddin, Sanjiv J Shah, Rowland W Chang, Robert Lafyatis, John Varga, Michael L. Whitfield

*Corresponding author for this work

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Heterogeneity in systemic sclerosis (SSc) confounds clinical trials. We previously identified intrinsic gene expression subsets by analysis of SSc skin. Here we test the hypotheses that skin gene expression signatures including intrinsic subset are associated with modified Rodnan skin score (MRSS) improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in 12 SSc patients' biopsies and 10 controls at baseline, and from serial biopsies of 1 cyclophosphamide-treated patient and 9 MMF-treated patients. Gene expression changes during treatment were determined using paired t-tests corrected for multiple hypothesis testing. MRSS improved in four of seven MMF-treated patients classified as the inflammatory intrinsic subset. Three patients without MRSS improvement were classified as normal-like or fibroproliferative intrinsic subsets. A total of 321 genes (false discovery rate (FDR)<5%) were differentially expressed at baseline between patients with and without MRSS improvement during treatment. The expression of 571 genes (FDR<10%) changed between pre-and post-MMF treatment biopsies for patients showing MRSS improvement. Gene expression changes in skin are only seen in patients with MRSS improvement. Baseline gene expression in skin, including intrinsic subset assignment, may identify SSc patients whose MRSS will improve during MMF treatment, suggesting that gene expression in skin may allow targeted treatment in SSc.

Original languageEnglish (US)
Pages (from-to)1979-1989
Number of pages11
JournalJournal of Investigative Dermatology
Volume133
Issue number8
DOIs
StatePublished - Jan 1 2013

Fingerprint

Systemic Scleroderma
Skin
Mycophenolic Acid
Gene expression
Gene Expression
Biopsy
Therapeutics
Genetic Association Studies
Genes
Skin Tests
Transcriptome
Cyclophosphamide
Clinical Trials

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Dermatology
  • Cell Biology

Cite this

Hinchcliff, Monique E ; Huang, Chiang Ching ; Wood, Tammara A. ; Matthew Mahoney, J. ; Martyanov, Viktor ; Bhattacharyya, Swati ; Tamaki, Zenshiro ; Lee, Julia ; Carns, Mary ; Podlusky, Sofia ; Sirajuddin, Arlene ; Shah, Sanjiv J ; Chang, Rowland W ; Lafyatis, Robert ; Varga, John ; Whitfield, Michael L. / Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis. In: Journal of Investigative Dermatology. 2013 ; Vol. 133, No. 8. pp. 1979-1989.
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title = "Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis",
abstract = "Heterogeneity in systemic sclerosis (SSc) confounds clinical trials. We previously identified intrinsic gene expression subsets by analysis of SSc skin. Here we test the hypotheses that skin gene expression signatures including intrinsic subset are associated with modified Rodnan skin score (MRSS) improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in 12 SSc patients' biopsies and 10 controls at baseline, and from serial biopsies of 1 cyclophosphamide-treated patient and 9 MMF-treated patients. Gene expression changes during treatment were determined using paired t-tests corrected for multiple hypothesis testing. MRSS improved in four of seven MMF-treated patients classified as the inflammatory intrinsic subset. Three patients without MRSS improvement were classified as normal-like or fibroproliferative intrinsic subsets. A total of 321 genes (false discovery rate (FDR)<5{\%}) were differentially expressed at baseline between patients with and without MRSS improvement during treatment. The expression of 571 genes (FDR<10{\%}) changed between pre-and post-MMF treatment biopsies for patients showing MRSS improvement. Gene expression changes in skin are only seen in patients with MRSS improvement. Baseline gene expression in skin, including intrinsic subset assignment, may identify SSc patients whose MRSS will improve during MMF treatment, suggesting that gene expression in skin may allow targeted treatment in SSc.",
author = "Hinchcliff, {Monique E} and Huang, {Chiang Ching} and Wood, {Tammara A.} and {Matthew Mahoney}, J. and Viktor Martyanov and Swati Bhattacharyya and Zenshiro Tamaki and Julia Lee and Mary Carns and Sofia Podlusky and Arlene Sirajuddin and Shah, {Sanjiv J} and Chang, {Rowland W} and Robert Lafyatis and John Varga and Whitfield, {Michael L.}",
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Hinchcliff, ME, Huang, CC, Wood, TA, Matthew Mahoney, J, Martyanov, V, Bhattacharyya, S, Tamaki, Z, Lee, J, Carns, M, Podlusky, S, Sirajuddin, A, Shah, SJ, Chang, RW, Lafyatis, R, Varga, J & Whitfield, ML 2013, 'Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis', Journal of Investigative Dermatology, vol. 133, no. 8, pp. 1979-1989. https://doi.org/10.1038/jid.2013.130

Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis. / Hinchcliff, Monique E; Huang, Chiang Ching; Wood, Tammara A.; Matthew Mahoney, J.; Martyanov, Viktor; Bhattacharyya, Swati; Tamaki, Zenshiro; Lee, Julia; Carns, Mary; Podlusky, Sofia; Sirajuddin, Arlene; Shah, Sanjiv J; Chang, Rowland W; Lafyatis, Robert; Varga, John; Whitfield, Michael L.

In: Journal of Investigative Dermatology, Vol. 133, No. 8, 01.01.2013, p. 1979-1989.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Molecular signatures in skin associated with clinical improvement during mycophenolate treatment in systemic sclerosis

AU - Hinchcliff, Monique E

AU - Huang, Chiang Ching

AU - Wood, Tammara A.

AU - Matthew Mahoney, J.

AU - Martyanov, Viktor

AU - Bhattacharyya, Swati

AU - Tamaki, Zenshiro

AU - Lee, Julia

AU - Carns, Mary

AU - Podlusky, Sofia

AU - Sirajuddin, Arlene

AU - Shah, Sanjiv J

AU - Chang, Rowland W

AU - Lafyatis, Robert

AU - Varga, John

AU - Whitfield, Michael L.

PY - 2013/1/1

Y1 - 2013/1/1

N2 - Heterogeneity in systemic sclerosis (SSc) confounds clinical trials. We previously identified intrinsic gene expression subsets by analysis of SSc skin. Here we test the hypotheses that skin gene expression signatures including intrinsic subset are associated with modified Rodnan skin score (MRSS) improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in 12 SSc patients' biopsies and 10 controls at baseline, and from serial biopsies of 1 cyclophosphamide-treated patient and 9 MMF-treated patients. Gene expression changes during treatment were determined using paired t-tests corrected for multiple hypothesis testing. MRSS improved in four of seven MMF-treated patients classified as the inflammatory intrinsic subset. Three patients without MRSS improvement were classified as normal-like or fibroproliferative intrinsic subsets. A total of 321 genes (false discovery rate (FDR)<5%) were differentially expressed at baseline between patients with and without MRSS improvement during treatment. The expression of 571 genes (FDR<10%) changed between pre-and post-MMF treatment biopsies for patients showing MRSS improvement. Gene expression changes in skin are only seen in patients with MRSS improvement. Baseline gene expression in skin, including intrinsic subset assignment, may identify SSc patients whose MRSS will improve during MMF treatment, suggesting that gene expression in skin may allow targeted treatment in SSc.

AB - Heterogeneity in systemic sclerosis (SSc) confounds clinical trials. We previously identified intrinsic gene expression subsets by analysis of SSc skin. Here we test the hypotheses that skin gene expression signatures including intrinsic subset are associated with modified Rodnan skin score (MRSS) improvement during mycophenolate mofetil (MMF) treatment. Gene expression and intrinsic subset assignment were measured in 12 SSc patients' biopsies and 10 controls at baseline, and from serial biopsies of 1 cyclophosphamide-treated patient and 9 MMF-treated patients. Gene expression changes during treatment were determined using paired t-tests corrected for multiple hypothesis testing. MRSS improved in four of seven MMF-treated patients classified as the inflammatory intrinsic subset. Three patients without MRSS improvement were classified as normal-like or fibroproliferative intrinsic subsets. A total of 321 genes (false discovery rate (FDR)<5%) were differentially expressed at baseline between patients with and without MRSS improvement during treatment. The expression of 571 genes (FDR<10%) changed between pre-and post-MMF treatment biopsies for patients showing MRSS improvement. Gene expression changes in skin are only seen in patients with MRSS improvement. Baseline gene expression in skin, including intrinsic subset assignment, may identify SSc patients whose MRSS will improve during MMF treatment, suggesting that gene expression in skin may allow targeted treatment in SSc.

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