Peripheral blood B cells subsets in patients with systemic lupus erythematosus: correlation with disease activity and organ involvement

Objectives: The aim of the study was to analyze the frequency and distribution of B cells subsets in a cohort of patients with SLE with different organ involvement and the possible correlation with disease activity.
Methods: 60 SLE patients (53 females; mean age 39.0±13.6 years; 29 with renal, 21 with articular, 4 with CNS, 4 with vascular and 2 with cutaneous involvement; 30 with an active disease-SLEDAI>10) and 30 healthy controls matched for age and sex were analyzed for the distribution of circulating PB B cell subpopulations by staining for CD19, CD38, and IgD in combination with the B cell memory marker CD27, by flow cytometry.
Results: Considering the Bm1-Bm5 classification, there was no difference in the percentage of B cells subpopulations between SLE patients and controls. Instead, SLE patients showed an higher percentage of CD19+/ZAP70+ cells (6.1±6.2%) compared with controls (2.1±1.4, p=0.01).
In SLE patients, disease activity index (SLEDAI) correlated positively with the percentage of CD19+ cells (r=0.43, p=0.001) and with the absolute number of CD19+/CD27+/IgD- (r= 0.42, p=0.004), CD19+/CD27+/CD38+ (r=0.37, p=0.01), CD19+/CD27-/IgD- (r=0.31, p=0.04) and CD19+/ZAP70+ (r=0.41, p=0.005).
SLE patients with an active disease had an higher percentage of CD19+ cells compared with patients with inactive disease (11.0±7.9% vs 4.4±4.2% respectively, p<0.001). Patients with active disease had an higher absolute number of memory cells (eBm5+Bm5 34±36/ul, CD19+/CD27+/IgD- 16±17), CD19+/CD27+CD38+ (10±13) and CD19+/ZAP70+ (7±10) compared with patients with inactive disease (eBm5+Bm5: 12±12, p=0.001; CD19+/CD27+/IgD-: 5±5, p<0.001; CD19+/CD27+CD38+: 3±3, p=0.001; CD19+/ZAP70+: 2±3, p=0.04). The distribution of Bm1-Bm5 and IgD/CD27 subsets was similar in patients with renal and articular involvement, even though considering only the subgroup with active disease, patients with renal involvement showed an higher percentage of memory B cells (eBm5+Bm5 36.3±21.2%) and of CD19+/CD27+CD38+ (11.8±8.6%) compared with patients with articular involvement (eBm5+Bm5: 15.0±8.5%, p=0.003; CD19+/CD27+CD38+: 5.0±4.0%, p=0.03). This difference was also confirmed by the ratio Bm2+Bm2'/eBm5+Bm5 in active renal disease (2.1±2.9) compared to 6.5±6.0 in active articular disease (p=0.005). Moreover, SLE patients with active renal disease had an higher percentage of CD19+/ZAP70+ cells (7.1±5.0) compared with patients with active articular involvement (3.3±2.6, p=0.04).
Conclusion: SLE patients showed a significant reduction of memory B cells compared with controls, regardless of the organ involvement. An increase of memory B cells appeared, however, in patients with renal active engagement, while an higher percentage of active cells was present in patients with active articular involvement.