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 Plasma Cell Gene Signature and Disease Characteristics in Systemic Lupus Erythematosus.

Petri1,  Michelle, Fang1,  Hong, Xu1,  Jie, Hu1,  Wenzheng, Akhter1,  Ehtisham, Bienkowska2,  Jadwiga, Allaire2,  Norm

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

Background/Purpose:

B cells, circulating plasma cells and tissue resident plasma cells contribute to the production of autoantibodies in SLE. The plasma cell populations have been suggested as an attractive therapeutic target. We investigated the association between clinical phenotype and circulating plasma cell signature in SLE.

Methods:

292 SLE patients (91% female, 59% Caucasian, 34% African-American, mean age 46.0 years) were enrolled in a prospective observational study. At baseline, the plasma cell gene signature (IGJ and TXNDC5) was determined in peripheral blood RNA using Affymetrix chips, and was divided into low (<7, 43.2%), medium (7 to 8, 28.4%) and high (>8, 28.4%) 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 cumulative history characteristics and plasma cell signature in SLE

VariableLow PC (<7) (%, N=126)Med PC (7–8) (%, N=83)High PC (>8) (%, N=83)P-valueAdjusted P-value for Race
Race     
  African-American19.139.850.6<.0001N.A.
  Caucasian74.654.239.8  
  Other6.46.09.6  
Malar rash53.250.649.40.860.99
Discoid rash16.716.921.70.610.80
Photosensitivity57.156.648.20.400.74
Oral Ulcers59.551.845.80.140.51
Arthritis69.880.774.70.210.35
Serositis49.250.643.40.600.62
Renal disorder45.239.845.80.670.26
Neurologic disorder10.38.412.10.750.72
Hematologic disorder68.367.577.10.300.28
Immunologic disorder80.285.590.40.130.28
ANA96.097.61000.190.09
Hematuria37.324.127.70.0990.027
Anemia61.172.375.90.0540.54
Leukopenia38.144.660.20.00670.021
Anti-dsDNA56.462.769.90.140.20
Lupus anticoagulant27.844.636.10.0430.031
Anti-Ro22.226.548.20.00020.0004
Anti-La11.19.820.50.080.031
Anti-RNP19.823.233.70.070.47
Low C352.453.065.10.150.17
Low C443.742.256.60.110.11
Increased ESR68.369.980.70.120.51

Table 2. Association between same-day visit disease activity and plasma cell signature in SLE

VariableLow PC (<7) (%, N=126)Med PC (7–8) (%, N=83)High PC (>8) (%, N=83)P-valueAdjusted P-value for Race
Physician global assessment >119.114.522.90.380.46
SLEDAI >=253.255.466.30.160.53
Immunosuppressive use45.222.932.50.00350.0008
Prednisone use42.130.130.10.110.025
NSAID27.031.315.70.0530.079
Statin31.015.716.90.0120.039

Table 3. Association between SLICC/ACR Damage Index and plasma cell signature in SLE

VariableLow PC (<7) (%, N=126)Med PC (7–8) (%, N=83)High PC (>8) (%, N=83)P-valueAdjusted P-value for Race
Cranial/peripheral Neuropathy14.310.83.60.0450.045
Deforming/Erosive arthritis5.811.10.00.0093too few

Results:

Elevated plasma cell gene signature was associated with leukopenia, anti-Ro, anti-La and the lupus anticoagulant, but not with the same day clinical activity by PGA or SLEDAI. It was negatively associated with neuropathy and arthritis damage but not associated with other organ damage (not shown in the table). Treatment with prednisone, immunosuppressive drugs and statins was associated with lower plasma cell gene signature.

Conclusion:

Surprisingly, the plasma cell signature was not associated with a more severe clinical activity phenotype, but with leukopenia and ENA. Immunosuppressive, prednisone and statin therapy was associated with lower plasma cell gene signature. The lack of association with clinical activity calls into question whether circulating plasma cells are the optimum therapeutic target in SLE. However, our assay does not account for tissue resident plasma cells.

To cite this abstract, please use the following information:
Petri, Michelle, Fang, Hong, Xu, Jie, Hu, Wenzheng, Akhter, Ehtisham, Bienkowska, Jadwiga, et al; Association Between Plasma Cell Gene Signature and Disease Characteristics in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1920
DOI:

Abstract Supplement

Meeting Menu

2011 ACR/ARHP