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Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins

  1. Christian S. Haas1,†,
  2. Chad J. Creighton1,
  3. Xiujun Pi1,
  4. Ira Maine1,
  5. Alisa E. Koch1,‡,
  6. G. Kenneth Haines III2,
  7. Song Ling1,
  8. Arul M. Chinnaiyan1,
  9. Joseph Holoshitz1,*

Article first published online: 27 JUN 2006

DOI: 10.1002/art.21953

Issue

Arthritis & Rheumatism

Arthritis & Rheumatism

Volume 54, Issue 7, pages 2047–2060, July 2006

Additional Information

How to Cite

Haas, C. S., Creighton, C. J., Pi, X., Maine, I., Koch, A. E., Haines, G. K., Ling, S., Chinnaiyan, A. M. and Holoshitz, J. (2006), Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease-discordant monozygotic twins. Arthritis & Rheumatism, 54: 2047–2060. doi: 10.1002/art.21953

Author Information

  1. 1

    University of Michigan Medical Center, Ann Arbor

  2. 2

    Northwestern University Feinberg Medical School, Chicago, Illinois

  1. †

    Dr. Haas and Mr. Creighton contributed equally to this work.

  2. ‡

    Dr. Koch is an incumbent of the Frederick G. L. Heutwell and William D. Robinson Professorial Chair in Rheumatology.

*5520D MSRB1, Box 0680, University of Michigan, 1150 West Medical Center Drive, Ann Arbor, MI 48109-0680

Publication History

  1. Issue published online: 27 JUN 2006
  2. Article first published online: 27 JUN 2006
  3. Manuscript Accepted: 30 MAR 2006
  4. Manuscript Received: 1 DEC 2005

Funded by

  • NIH. Grant Numbers: AI-47331, AR-46468, AR-20557, AR-48310, AI-40987, HL-58694, AR-48267
  • the Arthritis Foundation (Biomedical Research Grant)
  • Office of Research and Development, Department of Veterans Affairs
  • American Heart Association. Grant Number: AHA0423758Z
  • University of Michigan Cancer Biology Training Program
  • NIH. Grant Number: AR-07080

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Abstract

Objective

To identify disease-specific gene expression profiles in patients with rheumatoid arthritis (RA), using complementary DNA (cDNA) microarray analyses on lymphoblastoid B cell lines (LCLs) derived from RA-discordant monozygotic (MZ) twins.

Methods

The cDNA was prepared from LCLs derived from the peripheral blood of 11 pairs of RA-discordant MZ twins. The RA twin cDNA was labeled with cy5 fluorescent dye, and the cDNA of the healthy co-twin was labeled with cy3. To determine relative expression profiles, cDNA from each twin pair was combined and hybridized on 20,000-element microarray chips. Immunohistochemistry and real-time polymerase chain reaction were used to detect the expression of selected gene products in synovial tissue from patients with RA compared with patients with osteoarthritis and normal healthy controls.

Results

In RA twin LCLs compared with healthy co-twin LCLs, 1,163 transcripts were significantly differentially expressed. Of these, 747 were overexpressed and 416 were underexpressed. Gene ontology analysis revealed many genes known to play a role in apoptosis, angiogenesis, proteolysis, and signaling. The 3 most significantly overexpressed genes were laeverin (a novel enzyme with sequence homology to CD13), 11β-hydroxysteroid dehydrogenase type 2 (a steroid pathway enzyme), and cysteine-rich, angiogenic inducer 61 (a known angiogenic factor). The products of these genes, heretofore uncharacterized in RA, were all abundantly expressed in RA synovial tissues.

Conclusion

Microarray cDNA analysis of peripheral blood–derived LCLs from well-controlled patient populations is a useful tool to detect RA-relevant genes and could help in identifying novel therapeutic targets.

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