Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Association Between Interferon Alpha Gene Expression and Disease Characteristics in Systemic Lupus Erythematosus.

Petri1,  Michelle, Fang1,  Hong, Hu1,  Wenzheng, Bienkowska2,  Jadwiga, Allaire2,  Norm, Carulli2,  John, Linnik3,  Matthew D.

Johns Hopkins University School of Medicine, Baltimore, MD
Biogen Idec Inc., Cambridge, MA
Biogen Idec Inc., Solana Beach, CA

Background/Purpose:

The interferon alpha gene signature occurs in 50 to 70% of SLE patients and has been strongly associated with ENA (Ro, La, RNP). We investigated the association of the IFN gene signature in a cohort of Caucasian and African-American patients.

Methods:

272 SLE patients (92% female, 59% Caucasian, 33% African-American, mean age 46.0 years) were enrolled in a prospective observational study. At baseline, the IFN gene signature was determined in peripheral blood RNA using Affymetrix chips, and was divided into low (<8, 42.6%) and high (>=8, 57.4%) groups. Clinical associations, based on the cumulative history and the same-day visit disease activity, were then determined. The results were based on the chi-square test (SAS Institute, Cary, NC, USA). P-values were then adjusted for race. A p-value <=0.05 was considered statistically significant.

Table 1. Association between ACR criteria and IFN signature in SLE

VariableLow IFN (%, N=116)High IFN (%, N=156)P-valueAdjusted P-value for Race
Malar rash52.351.90.910.82
Discoid rash14.719.20.320.30
Photosensitivity58.651.30.230.45
Oral Ulcers57.850.60.240.45
Arthritis75.973.10.600.45
Serositis49.148.10.860.89
Renal disorder36.249.40.0310.23
Neurologic disorder12.97.70.150.19
Hematologic disorder60.376.30.00480.0038
Immunologic disorder81.987.20.230.38
ANA positivity95.798.70.120.18

Table 2. Association between cumulative history characteristics and IFN signature in SLE

VariableLow IFN (%, N=116)High IFN (%, N=156)P-valueAdjusted P-value for Race
Race    
  African-American29.336.5<.0001N.A.
  Caucasian70.750.6  
  Other0.012.8  
Pericarditis15.727.60.020.024
Proteinuria36.249.40.0310.23
Anemia61.275.00.0150.12
Coombs11.224.50.00550.0069
Leukopenia33.653.90.00090.0018
Anti-DNA45.773.7<.0001<.0001
Anti-Sm10.325.80.00140.013
Anti-Ro14.745.5<.0001<.0001
Anti-La6.919.40.00350.0035
Anti-RNP11.237.4<.0001<.0001
Low C342.266.7<.00010.0011
Low C432.858.3<.00010.0002

Table 3. Association between same-day visit disease activity and IFN signature in SLE

VariableLow IFN (%, N=116)High IFN (%, N=156)P-valueAdjusted P-value§
Physician Global Assessment (>1)12.923.10.0340.19
SLEDAI ('2)46.666.70.00090.004
Modified SLEDAI* (>1)34.546.80.0420.2
Age at visit (years)    
  <= 307.815.40.0570.17
  > 3092.284.6  
Urine Protein/Creatinine Ratio (>=0.5)6.913.50.0830.70
Anti-dsDNA7.833.3<.0001<.0001
Low C35.218.00.00160.0012
Low C45.216.00.00530.0032
ESR (>20)40.458.40.00340.034
* Modified SLEDAI (SLEDAI without low complement or anti-dsDNA)
§ Adjusted for race unless specified
£ Adjusted for race, prednisone dose and immunosuppressive (yes/no)

Table 4. Association between SLICC/ACR Damage Index and IFN signature in SLE

VariablesLow IFN (%, N=116)High IFN (%, N=156)P-valueAdjusted P-value for Race
Cataract31.016.00.00330.0027
Cognitive impairment12.95.10.0220.02
Valvular disease6.01.30.030.06
Muscle atrophy or weakness5.21.30.0760.068
AVN7.817.40.020.018

Results:

The high interferon alpha signature group was associated with non-Caucasian race, younger age, autoantibodies, and low complement. Clinical associations included leukopenia and pericarditis. The high IFN signature was not associated with clinical disease activity at the same day, once low complement and anti-dsDNA were removed from the SLEDAI.

Conclusion:

IFN signature was strongly associated with Coombs positivity, leukopenia, autoantibodies, and low complement, but not with clinical disease activity. Surprisingly, SLE patients with this signature had a lower risk of developing some organ damage including cataract, cognitive impairment, valvular disease, and muscle atrophy/weakness.

To cite this abstract, please use the following information:
Petri, Michelle, Fang, Hong, Hu, Wenzheng, Bienkowska, Jadwiga, Allaire, Norm, Carulli, John, et al; Association Between Interferon Alpha Gene Expression and Disease Characteristics in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1919
DOI:

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