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Comparative Study
. 2011 Dec;63(12):3931-41.
doi: 10.1002/art.30598.

B lymphocyte stimulator levels in systemic lupus erythematosus: higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels

Lauren L Ritterhouse  1 , Sherry R Crowe, Timothy B Niewold, Joan T Merrill, Virginia C Roberts, Amy B Dedeke, Barbara R Neas, Linda F Thompson, Joel M Guthridge, Judith A James
Affiliations
Comparative Study

B lymphocyte stimulator levels in systemic lupus erythematosus: higher circulating levels in African American patients and increased production after influenza vaccination in patients with low baseline levels

Lauren L Ritterhouse et al. Arthritis Rheum. 2011 Dec.

Abstract

Objective: To examine the relationship between circulating B lymphocyte stimulator (BLyS) levels and humoral responses to influenza vaccination in systemic lupus erythematosus (SLE) patients, as well as the effect of vaccination on BLyS levels, and to investigate clinical and serologic features of SLE that are associated with elevated BLyS levels.

Methods: Clinical history, disease activity measurements, and blood specimens were collected from 60 SLE patients at baseline and after influenza vaccination. Sera were tested for BLyS levels, lupus-associated autoantibodies, serum interferon-α (IFNα) activity, 25-hydroxyvitamin D (25[OH]D), and humoral responses to influenza vaccination.

Results: Thirty percent of the SLE patients had elevated BLyS levels, with African American patients having higher BLyS levels than white patients (P = 0.006). Baseline BLyS levels in patients were not correlated with humoral responses to influenza vaccination (P = 0.863), and BLyS levels increased postvaccination only in the subset of patients with BLyS levels in the lowest quartile (P = 0.0003). Elevated BLyS levels were associated with increased disease activity, as measured by the SLE Disease Activity Index, physician's global assessment, and Systemic Lupus Activity Measure in white patients (P = 0.035, P = 0.016, and P = 0.018, respectively), but not in African Americans. Elevated BLyS levels were also associated with anti-nuclear RNP (P = 0.0003) and decreased 25(OH)D (P = 0.018). Serum IFNα activity was a significant predictor of elevated BLyS in a multivariate analysis (P = 0.002).

Conclusion: Our findings indicate that African American patients with SLE have higher BLyS levels regardless of disease activity. Humoral response to influenza vaccination is not correlated with baseline BLyS levels in SLE patients, and only those patients with low baseline BLyS levels demonstrate an increased BLyS response after vaccination.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. African American SLE patients have increased plasma BLyS levels
A, BLyS levels (ng/mL) in SLE patients and matched controls. Each symbol represents one individual and the median and interquartile range (IQR) is displayed. Mann Whitney test was performed. B, BLyS levels (ng/mL) in African American and European American patients. Boxes represent median and IQR. Mann Whitney tests were performed.
Figure 2
Figure 2. No association between baseline BLyS levels and influenza vaccination responses in SLE patients
A, Baseline BLyS levels and correlation with influenza vaccination response as measured by a combined antibody score (Bmax, Ka, HAI) in SLE patients (r2=0.001, p=0.863). B, BLyS levels at baseline and 2 weeks after vaccination in all 60 SLE patients (p=0.337). C, BLyS levels at baseline and 2 weeks after vaccination in the subset of SLE patients in the lowest quartile (n=15) of baseline BLyS levels. Each symbol represents one individual.
Figure 3
Figure 3. Elevated BLyS levels are associated with increased disease activity in European American SLE patients but not in African American SLE patients
SLEDAI (Panel A) and PGA (Panel B) scores in European American patients. SLEDAI (Panel C) and PGA (Panel D) scores in African American patients (p=1.000 and p=0.837, respectively). Elevated BLyS levels were defined as being greater than the 95th percentile of healthy matched controls. Median and IQR displayed. Each symbol represents one individual.
Figure 4
Figure 4. Serum IFN-α activity is positively correlated with circulating BLyS levels in SLE patients
A, Correlation between IFN-α activity and BLyS levels. Black circles and gray squares represent individual African American and European American patients, respectively. Spearman correlation was performed. B, Serum IFN-α activity in patients with normal and elevated BLyS levels. Elevated BLyS levels were defined as being greater than the 95th percentile of healthy matched controls. Bars represent median and IQR.
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