Identification of genes modulated in rheumatoid arthritis using complementary DNA microarray analysis of lymphoblastoid B cell lines from disease‐discordant monozygotic twins
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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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CCN1 is among the most highly differentially expressed genes in rheumatoid arthritis in disease-discordant monozygotic twins.
“Genomic studies have found that CCN1 is among the most highly differentially expressed genes in rheumatoid arthritis in disease-discordant monozygotic twins [133].”
From CCN1/CYR61: the very model of a modern matricellular protein (2011) · cites this paper as [133]
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- Authors
- Haas, C. S., Creighton, C. J., Pi, X., Maine, I., Koch, A. E., Haines, G. K., Ling, S., Chinnaiyan, A. M., & Holoshitz, J.
- Affiliations
- University of Michigan (US)
- Northwestern University (US)
- Venue
- Arthritis & Rheumatism
- Publisher
- Wiley
- Published
- 2006-06-27
- Volume
- 54
- Issue
- 7
- Pages
- 2047-2060
- ISSN
- 0004-3591 (ISSN-L)
- 1529-0131
- OpenAlex
- W2069539988
- Cited by
- 102
- References
- 56
- Citations by year
- 2025: 2 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 1 · 2019: 5 · 2018: 6 · 2017: 1 · 2016: 7 · 2015: 4 · 2014: 10 · 2013: 4 · 2012: 8
- FWCI
- 6.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Arthritis & Rheumatism (publishedVersion)
- PubMed (publishedVersion)
- Deep Blue (University of Michigan) (submittedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- Arthritis Foundation
- Office of Research and Development
- University of Michigan
- National Institutes of Health
- National Heart, Lung, and Blood Institute (HL58694)
- National Institute of Allergy and Infectious Diseases (R01AI047331, AI40987, AI47331)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR048310, P60AR020557, AR20 557, AR-48310, AR07080, R01AR048267, AR48267, R01AR046468, AR-46468, T32AR007080)
- Topics
- Health Sciences › Medicine › Rheumatology › Rheumatoid Arthritis Research and Therapies
- Health Sciences › Medicine › Hematology › Autoimmune and Inflammatory Disorders Research
- Health Sciences › Medicine › Complementary and alternative medicine › Natural Compounds in Disease Treatment
- Keywords
- rheumatoid arthritis, gene expression profiling, lymphoblastoid cell lines, monozygotic twins, discordant twins, synovium, 11β-hydroxysteroid dehydrogenase type 2, apoptosis, angiogenesis, therapeutic target
- MeSH terms
- Arthritis, Rheumatoid, B-Lymphocytes, Cell Line, Diseases in Twins, Gene Expression Regulation, Humans, Inflammation, Osteoarthritis, Synovial Membrane, Twins, Monozygotic, Apoptosis, Immediate-Early Proteins, DNA, Complementary, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Intercellular Signaling Peptides and Proteins, Angiogenic Proteins, 11-beta-Hydroxysteroid Dehydrogenase Type 2, Metalloproteases, Cysteine-Rich Protein 61
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