Background B-cell–activating factor (BAFF; also known as B lymphocyte stimulator or BLyS) is a prominent factor in the selection and survival of B cells. BAFF has been demonstrated to be elevated in the blood of systemic lupus erythematosus (SLE) patients and is implicated in the pathogenesis of the disease. We have shown that BAFF gene expression level (mRNA) in whole blood associates with same day disease activity and predicts future activity in SLE patients. The concentration of the BAFF protein in serum has also been used as a marker of disease activity. In this study, we investigated the utility of BAFF mRNA versus protein level as a predictor of future global disease activity in SLE patients.
Methods 292 patients (59% Caucasian, 34% African-American, 92% female, mean age 46 ± 12 years) were enrolled in a prospective observational study. At baseline, BAFF gene expression level was measured in peripheral blood RNA (PAXgene) using quantitative PCR. Serum BAFF (protein) levels were measured using the Rules Based Medicine platform. The number of visits per patient over the following year ranged from 1–9. Six patients had 1 visit, 46 patients had 2–3 visits, 159 patients had 4 visits, and 81 patients had more than 4 visits. P-values were calculated using generalised estimating equations as implemented in SAS 9.2. P-values were then adjusted for ethnicity.
Results By two separate measures, PGA (physician global assessment) and SLEDAI, higher levels of measured BAFF mRNA were associated with higher levels of disease activity. The association with SLEDAI was stronger. Multiple measures of disease activity including proteinuria, anti-dsDNA antibodies and hypocomplementemia were also associated with higher levels of BAFF mRNA. This same association was NOT seen with the serum BAFF protein. Higher levels of BAFF protein were only associated with elevated anti-dsDNA antibodies, not global measures of disease activity.
Conclusion BAFF mRNA at the baseline visit was strongly associated with global disease activity, urine protein/creatinine ≥0.5, serologies, and ESR over the next year. In contrast, BAFF protein level in the blood at baseline only correlated with anti-dsDNA over the next year. This study supports the use of BAFF mRNA level in peripheral blood rather than protein as a predictive biomarker of disease activity in SLE patients.