Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Elevated BLyS Levels Are Associated with an Increase in Autoantibody Specificites and ANA Titer in Systemic Lupus Erythematosus.
Ritterhouse3, Lauren L., Moyer3, Amanda R., Roberts2, Virginia C., Dedeke2, Amy B., Crowe3, Sherry R., Air4, Gillian M., Thompson3, Linda F.
B Lymphocyte Stimulator (BLyS) is a cytokine that belongs to the TNF ligand family, and has been shown to play an important role in the proliferation and differentiation of B cells. Elevated serum levels of BLyS have been demonstrated in autoimmune disease patients, including those with SLE. BLyS is hypothesized to contribute to SLE pathogenesis by affecting survival signals and apoptosis of autoantibody-producing B cells. In this study we seek to investigate the relationship between serum BLyS levels and humoral autoimmunity, as well as the effect of serum BLyS on an antigen-specific humoral immune response.
This study enrolled 61 female SLE patients who met ACR criteria. BLyS levels were measured by a quantitative sandwich enzyme immunoassay. Lupus-associated autoantibodies (Ro, La, Sm, nRNP, ribosomal P, dsDNA, ANAs and phospholipid antibodies) and influenza vaccination humoral immune response parameters including Bmax (relative amounts of anti-influenza antibodies against native antigen), Ka (relative affinity), and hemagglutination inhibition (relative protective antibody response) were measured. SLE patients were given a cumulative index score based on these three vaccination response parameters and classified as being either a "high responder" (greater than the median cumulative index score) or a "low responder" (less than the median cumulative index score).
African Americans (AA, n=24) had significantly (p=0.021, unpaired t-test) higher serum BLyS levels than did European Americans (EA, n=35) (1649 ± 224 pg/mL in AA versus 1045 ± 144 pg/mL in EA). No differences were seen in BLyS levels between high responders to influenza vaccination (n=31) and low responders (n=30) (p=0.72, unpaired t-test). SLE patients with greater than or equal to 2 autoantibody specificities had higher BLyS levels than those patients with less than 2 specificities (p=0.035, unpaired t-test with Welch's correction). Additionally, BLyS levels were increased in patients with an ANA titer of greater than 1:120 (p=0.0012, unpaired t-test with Welch's correction). ACR classification criteria and disease activity measures were assessed in relation to serum BLyS levels. Increased serum BLyS correlated with an increase in disease damage as measured by SLICC (r2=0.12, p=0.006), and an increase in disease activity as measured by PGA (r2=0.10, p=0.013), and SLAM (r2=0.07, p=0.046). Patients with the criteria discoid rash, proteinuria, and lymphopenia had higher serum BLyS levels than did those patients without these criteria (p=0.029, p=0.011, and p=0.008, respectively, unpaired t-test).
Increased serum BLyS levels were observed in African Americans, but were not associated with the ability to make a humoral response to influenza vaccination. Elevated BLyS levels were also associated with an increase in number of autoantibody specificities, as well as an increase in ANA titer. Additionally, increased disease activity measures correlated with increased serum BLyS levels. This evidence strongly supports the role for BLyS in humoral autoimmunity and SLE disease pathogenesis.
To cite this abstract, please use the following information:
Ritterhouse, Lauren L., Moyer, Amanda R., Roberts, Virginia C., Dedeke, Amy B., Crowe, Sherry R., Air, Gillian M., et al; Elevated BLyS Levels Are Associated with an Increase in Autoantibody Specificites and ANA Titer in Systemic Lupus Erythematosus. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :24