Circulating memory B cells characterize active nephritis instead activated naïve B cells are expanded in active articular involvement in patients with systemic lupus erythematosus (SLE)

Background: Autoreactive B cells and plasma cells appear to be of central importance in the pathogenesis of SLE. The heterogeneity of the B cell compartment is known and B cell subsets could be differently expressed in certain phases of SLE or in accordance to organ involvement, but their role is still largely to be defined.
Objectives: To analyze B cells subsets distribution and inflammatory molecules in a cohort of patients with SLE and the association with different organ involvement and disease activity.
Methods: 111 SLE patients (98 females (83%); mean age 37.8±12.8 years; 53 with renal, 32 with articular, 26 with others organ involvements; 57 with an active disease-SLEDAI≥4) and 30 healthy controls matched for age and sex were analyzed for the distribution of circulating peripheral blood B cell subpopulations by staining for surface markers CD45, CD19, CD38, IgD (Bm1-Bm5 B cells classification (1)) and intracellular marker ZAP-70 (2) by flow cytometry. BAFF and IL6 plasma levels were analyzed by ELISA.
Results: There was no difference in B cells subpopulations between SLE patients and controls. Instead, SLE patients showed an higher percentage of CD19+/ZAP-70+ cells (7.9±6.9%) compared with controls (2.1±1.4, p<0.001) and higher plasma levels of IL6 (6.2±18.7 vs 0.9±0.9 pg/ml p=0.02) and BAFF (1718±1767 vs 425±175 pg/ml, p<0.001).
In SLE patients, disease activity index (SLEDAI) directly correlated with the plasma levels of IL6 (r=0.59, p<0.001) and with the percentage of CD19+/ZAP-70+ cells (r=0.30, p=0.003).
SLE patients with an active disease had higher levels of IL6 (9.7±24.8 vs 2.0±3.4, p<0.001) and higher percentage of CD19+/ZAP-70 positive cells (9.2±7.5 vs 6.3±5.9, p=0.05) compared to patients with inactive disease, whereas no differences were seen in B cell subsets distribution.
Dividing SLE patients by organ involvement, the 29 subjects with active renal involvement had a lower Bm2+Bm2'/eBm5+Bm5 ratio (1.3±1.3 vs 5.7±17.1, p=0.04) and higher percentages of CD19/ZAP-70+ cells (12.0±8.2 vs 5.4±4.2, p=0.003) compared to 24 patients with nephritis remission. Moreover, in patients with renal involvement the percentage of B cells ZAP-70+ inversely correlated with the Bm2+Bm2'/eBm5+Bm5 ratio (r=-0.54, p<0.001).
The 16 patients with active articular involvement showed higher percentage of Bm2+Bm2' cells (naïve 'activated' B cells) compared to 16 patients with inactive articular involvement (56.9±17.2 vs 41.7±16.5%, p=0.03) and lower percentages of eBm5+Bm5 cells (memory B cells: 17.1±12.0 vs 32.4±14.5%, p=0.004).
SLE patients with active renal disease differed from those with active articular involvement for a lower Bm2+Bm2'/eBm5+Bm5 ratio (p<0.001) and for an higher percentage of CD19+/ZAP-70+ cells (p=0.02).
No differences in B cells subset distribution was seen between renal and articular involvement in patients with inactive disease.
Conclusions: In SLE patients an increase of memory B cells occur in subjects with renal active disease, while an higher percentage of active cells is present in patients with active articular involvement. The presence of B cells ZAP70+ seems to characterize active disease, in particular in patients with active renal involvement.
References:[span]
1. Binard et al. ARD 2009[/li]
2. Tolusso et al. Clin Immunol 2009