Background/Purpose: 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 microarray (Affymetrix) and confirmed with 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 generalized estimating equations as implemented in SAS 9.2. P-values were then adjusted for ethnicity.

Results:

Table 1 shows the association of BAFF mRNA with SLE global activity (physician global assessment, PGA; and SLEDAI) over the next year, as well as renal activity, serologies and ESR over the next year. Table 2 shows the association of BAFF protein with the same disease parameters.

Table 1: Association of baseline BAFF mRNA level with percentage of visits with disease activity over the subsequent year

 

Variable	Low BAFF (<10.7) N visits=387	Med BAFF (10.7-11.4) N visits=476	High BAFF (>11.4) N visits=347	Adjusted P-value for ethnicity
Physician global assessment >1	8%	21%	24%	0.0041
SLEDAI ≥2	36%	57%	71%	<0.0001
Urine Protein/Creatinine Ratio (≥0.5)	3%	13%	13%	0.0096
Anti-dsDNA ≥ 10	9%	21%	35%	<0.0001
C3 <79 mg/dL	4%	11%	21%	0.0004
C4 <12 mg/dL	4%	11%	19%	0.0005
ESR >20	35%	55%	63%	0.0005

Table 2: Association of baseline BAFF protein level with percentage of visits with disease activity over the subsequent year

 

Variable	Low (<950 pg/ml) N patients=96 N visits=405	Med (950-1400 pg/ml) N patients=98 N visits=404	High (>1400 pg/ml) N patients=98 N visits=401	P-value	Adjusted P-value for ethnicity
Physician global assessment >1	17%	15%	21%	0.49	0.53
SLEDAI ≥2	51%	52%	60%	0.30	0.073
Urine Protein/Creatinine Ratio (≥0.5)	9%	7%	12%	0.39	0.38
Anti-dsDNA ≥ 10	18%	14%	32%	0.0036	0.0031
C3 <79 mg/dL	7%	10%	18%	0.052	0.090
C4 <12 mg/dL	9%	7%	16%	0.090	0.14
ESR >20	45%	51%	55%	0.25	0.11

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.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/only-baff-mrna-not-baff-protein-level-in-blood-is-associated-with-sle-activity-over-one-year/