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 B-Cell Activating Factor Gene Expression and Disease Characteristics in Systemic Lupus Erythematosus.
Petri1, Michelle, Hu1, Wenzheng, Fang1, Hong, Xu1, Jie, Bienkowska2, Jadwiga, Allaire2, Norm, Carulli2, John
Johns Hopkins University School of Medicine, Baltimore, MD
Biogen Idec Inc., Cambridge, MA
Biogen Idec Inc., Solana Beach, CA
Background/Purpose:
Multiple gene expression signatures occur in SLE. Because of the interest in anti-BAFF therapy in SLE, we explored the association between BAFF gene expression and clinical observations in SLE patients.
Methods:
292 SLE patients (58.9% Caucasian, 33.9% African-American, 91.1% female, mean age 46.0±11.9 years) were enrolled in a prospective observational study. At baseline, the BAFF gene expression levels were determined in peripheral blood RNA using Affymetrix chips. 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.
BAFF gene expression was high (> 11.4) in 28.8%, medium (10.7–11.4) in 37.7% and low (<10.7) in 33.6%. Medium to high signature was more common in African-Americans than Caucasians. Clinically, the gene signature was associated with more leukopenia and serologically with Coombs, more autoantibodies (anti-dsDNA, anti-Sm, anti-Ro, anti-La, and anti-RNP) and low complement. However, it was not associated with antiphospholipid antibodies (not shown in the table). The same-day visit disease activity was found to be higher in higher BAFF group. In terms of SLICC/ACR Damage Index, the gene expression was associated with less cataract, cognitive impairment and chronic seizure but not associated with other organ damage (not shown in the table).
Results:
Table 1. Association between cumulative history characteristics and BAFF in SLE
| Variable | Low BAFF (<10.7) (%, N=98) | Med BAFF (10.7–11.4) (%, N=110) | High BAFF (>11.4) (%, N=84) | P-value | Adjusted P-value for Race |
|---|---|---|---|---|---|
| Race African-American | 27.6 | 39.1 | 34.5 | 0.005 | N.A. |
| Caucasian | 70.4 | 54.6 | 51.2 | ||
| Other | 2.0 | 6.4 | 14.3 | ||
| Malar rash | 51.0 | 56.4 | 45.2 | 0.31 | 0.30 |
| Discoid rash | 15.3 | 21.8 | 16.7 | 0.44 | 0.61 |
| Photosensitivity | 61.2 | 51.8 | 50.0 | 0.25 | 0.47 |
| Oral Ulcer | 63.3 | 48.2 | 48.8 | 0.057 | 0.13 |
| Arthritis | 76.5 | 74.6 | 71.4 | 0.73 | 0.61 |
| Serositis | 46.9 | 51.8 | 44.1 | 0.55 | 0.60 |
| Neurologic disorder | 13.3 | 12.7 | 3.6 | 0.056 | 0.042 |
| Hematologic disorder | 64.3 | 76.4 | 70.2 | 0.16 | 0.16 |
| Immunologic disorder | 82.7 | 84.6 | 86.9 | 0.73 | 0.87 |
| ANA | 95.9 | 98.2 | 98.8 | 0.39 | 0.50 |
| Proteinuria | 34.7 | 45.5 | 52.4 | 0.05 | 0.25 |
| Hematuria | 22.5 | 35.5 | 34.5 | 0.09 | 0.20 |
| Seizure | 11.2 | 10.0 | 2.4 | 0.066 | 0.065 |
| Hemolytic anemia | 10.2 | 9.1 | 9.5 | 0.96 | 0.87 |
| Coombs | 6.1 | 22.0 | 25.0 | 0.0011 | 0.0005 |
| Leukopenia | 33.7 | 48.2 | 58.3 | 0.0035 | 0.0064 |
| Anti-dsDNA | 48.0 | 65.5 | 73.8 | 0.0010 | 0.0043 |
| Anti-Sm | 9.2 | 20.0 | 27.7 | 0.0054 | 0.026 |
| Anti-Ro | 11.2 | 32.7 | 51.2 | <.0001 | <.0001 |
| Anti-La | 5.1 | 13.6 | 22.9 | 0.0022 | 0.0019 |
| Anti-RNP | 9.2 | 29.1 | 37.4 | <.0001 | 0.0002 |
| Low C3 | 45.9 | 53.6 | 71.4 | 0.002 | 0.012 |
| Low C4 | 32.7 | 46.4 | 64.3 | 0.0001 | 0.0005 |
| Increased ESR | 64.3 | 77.3 | 75.0 | 0.091 | 0.30 |
Table 2. Association between same-day visit disease activity and BAFF in SLE
| Variable | Low BAFF (<10.7) (%, N=98) | Med BAFF (10.7–11.4) (%, N=110) | High BAFF (>11.4) (%, N=84) | P-value | Adjusted P-value for Race |
|---|---|---|---|---|---|
| Physician global assessment >1 | 9.2 | 20.9 | 27.4 | 0.006 | 0.026 |
| SLEDAI >=2 | 35.7 | 66.4 | 71.4 | <.0001 | <.0001 |
| Age at visit <= 30 | 7.1 | 12.7 | 16.7 | 0.14 | 0.27 |
| > 30 | 92.9 | 87.3 | 83.3 | ||
| Urine Protein/Creatinine Ratio (>=0.5) | 3.1 | 13.6 | 15.5 | 0.011 | 0.058 |
| Anti-dsDNA >= 10 | 10.2 | 19.1 | 39.3 | <.0001 | <.0001 |
| C3 <79 | 5.1 | 13.6 | 19.1 | 0.015 | 0.011 |
| C4 <12 | 4.1 | 11.8 | 17.9 | 0.012 | 0.0064 |
| ESR >20 | 36.5 | 54.7 | 63.1 | 0.001 | 0.0077 |
Table 3. Association between SLICC/ACR Damage Index and BAFF in SLE
| Variable | Low BAFF (<10.7) (%, N=98) | Med BAFF (10.7–11.4) (%, N=110) | High BAFF (>11.4) (%, N=84) | P-value | Adjusted P-value for Race |
|---|---|---|---|---|---|
| Cataract | 30.6 | 23.6 | 9.5 | 0.0024 | 0.0011 |
| Cognitive impairment | 16.3 | 7.3 | 2.4 | 0.0033 | 0.0027 |
| Seizure | 9.2 | 4.6 | 1.2 | 0.048 | 0.078 |
Conclusion:
BAFF gene expression level is strongly associated with Coombs positivity, leukopenia, autoantibodies and low complement. Surprisingly, it is negatively associated with neurological damage. The associations between BAFF gene expression and clinical characteristics were studied at the RNA level and need to be verified at the protein level.
To cite this abstract, please use the following information:
Petri, Michelle, Hu, Wenzheng, Fang, Hong, Xu, Jie, Bienkowska, Jadwiga, Allaire, Norm, et al; Association between B-Cell Activating Factor Gene Expression and Disease Characteristics in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :585
DOI:
