Systemic sclerosis and lupus: points in an interferon-mediated continuum.

Abstract

OBJECTIVE:

To investigate peripheral blood (PB) cell transcript profiles of systemic sclerosis (SSc) and its subtypes in direct comparison with systemic lupus erythematosus (SLE).

METHODS:

We investigated PB cell samples from 74 SSc patients, 21 healthy controls, and 17 SLE patients using Illumina Human Ref-8 BeadChips and quantitative polymerase chain reaction confirmation. None of the study participants were receiving immunosuppressive agents other than low-dose steroids and hydroxychloroquine. In addition to conventional statistical and modular analysis, a composite score for the interferon (IFN)-inducible genes was calculated. Within the group of patients with SSc, the correlation of the IFN score with the serologic and clinical subtypes was investigated, as were single-nucleotide polymorphisms in a selected number of IFN pathway genes.

RESULTS:

Many of the most prominently overexpressed genes in SSc and SLE were IFN-inducible genes. Forty-three of 47 overexpressed IFN-inducible genes in SSc (91%) were similarly altered in SLE. The IFN score was highest in the SLE patients, followed by the SSc patients, and then the controls. The difference in IFN score among all 3 groups was statistically significant (P < 0.001 for all 3 comparisons). SSc and SLE PB cell samples showed striking parallels to our previously reported SSc skin transcripts in regard to the IFN-inducible gene expression pattern. In SSc, the presence of antitopoisomerase and anti-U1 RNP antibodies and lymphopenia correlated with the higher IFN scores (P = 0.005, P = 0.001, and P = 0.004, respectively); a missense mutation in IFNAR2 was significantly associated with the IFN score.

CONCLUSION:

SLE and SSc fit within the same spectrum of IFN-mediated diseases. A subset of SSc patients shows a "lupus-like" high IFN-inducible gene expression pattern that correlates with the presence of antitopoisomerase and anti-U1 RNP antibodies.

• Authors: Shervin Assassi, Maureen D Mayes, Frank C Arnett, Pravitt Gourh, Sandeep K Agarwal, Terry A McNearney, Damien Chaussabel, Nancy Oommen, Michael Fischbach, Kairav R Shah, Julio Charles, Virginia Pascual, John D Reveille, Filemon K Tan
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 62 Issue 2 Pg. 589-98 (Feb 2010) ISSN: 0004-3591 [Print] United States
• PMID: 20112391 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Autoantibodies
• IFNAR2 protein, human
• Ribonucleoprotein, U1 Small Nuclear
• Receptor, Interferon alpha-beta
• Interferons

Topics

• Adult
• Aged
• Autoantibodies (blood)
• Female
• Gene Expression Profiling
• Genetic Variation
• Humans
• Interferons (genetics, immunology)
• Leukocytes (physiology)
• Lupus Erythematosus, Systemic (genetics, immunology)
• Male
• Middle Aged
• Oligonucleotide Array Sequence Analysis
• Polymorphism, Single Nucleotide
• Quantitative Trait, Heritable
• Receptor, Interferon alpha-beta (genetics)
• Ribonucleoprotein, U1 Small Nuclear (genetics)
• Scleroderma, Systemic (genetics, immunology)