Background B cells play an important role in Systemic Sclerosis (SSc).
Objectives To determine the phenotypic characteristics of blood B cell subsets in patients with SSc and their possible association with organ involvement and disease activity.
Methods 100 SSc patients (83.0% females; mean age 56.5±13.9 years; 49 (49.0%) with diffuse skin involvement-dcSSc) and 50 age and sex matched healthy controls (HC) were studied. Clinical, immunological and inflammatory characteristics were assessed for all the SSc patients. Peripheral blood samples were analyzed by flow cytometry for the distribution of circulating B cell subpopulations by staining with surface markers CD45, CD19, CD38, CD27 and IgD (1). For each patient at study entry, disease activity and severity were evaluated (2,3). Patients with an activity score ≥3.0 were considered to have an active disease.
Results The distribution of circulating CD19+ cells of SSc patients and healthy controls was comparable. Considering the two main phenotypes of the disease, the percentage of CD19+ cells was lower in patients with dSSc versus HC (8.0±4.8%vsHC 10.6±3.3%, p=0.01), as well as versus patients with limited skin disease (lSSc) (11.3±5.3%, p=0.01). The percentage of CD19 cells inversely correlated with activity index (R=-0.36, p=0.001) and patients with active disease showed lower percentage of CD19 (8.1±4.2%) compared with patients with inactive disease (11.6±5.9%, p=0.001). ROC curve analysis showed a CD19 cut off of 5.5% as the one that identified patients with active disease (AUC=0.31, p=0.006). Patients with CD19 higher than 5.5% more frequently presented a diffuse disease (p=0.02) and a restrictive lung involvement (p=0.001). The analysis of B cell subsets showed a lower percentage of pre-switched memory B cells (IgD+CD27+: 7.9±8.3p<0.001) and an higher percentage of naïve B cells (IgD+CD27-: 70.7±16.9, p=0.001) in SSc patients with respect to HC (IgD+CD27+:13.3±8.3,p<0.001;IgD+CD27-:64.4±11.1,p=0.001). An higher percentage of naïve B cells and a lower percentage of pre-switched memory B cells were confirmed either for diffuse (IgD+CD27-:8.4±9.3%; IgD+CD27+: 69.5±18.9%) or the limited subset of the disease (IgD+CD27-: 7.4±7.5%; IgD+CD27+: 71.4±19.0%) with respect to HC (p<0.02 for all comparisons).Furthermore an higher percentage of plasmablasts (CD38+CD27+: 4.0±4.5%) was observed in dSSc patients compared to HC (2.0±2.6%, p=0.004) and compared with the limited disease (2.2±2.8%, p=0.003). Considering organ involvement, an higher percentage of plasmablast (3.9±3.4) characterized patients with restrictive lung disease (FVC<79%) with respect to patients with FVC>79% (2.9±3.9%, p=0.01).
Conclusions Systemic sclerosis patients show an immune deregulation of B cell subset phenotypes in the peripheral blood. The difference in the percentage of CD19 population in the different subsets of the disease and when the disease is active suggests that the CD19 count may be a potential simple biomarker of the activity. Plasmablasts represent crucial biomarkers of dSSc with lung involvement.
Tolusso B et al; Clin Immunol. 2009.
Medsger TA et al; Clin Exp Rheumatol 2003.
Valentini G et al; Clin Exp Rheumatol 2003.
Disclosure of Interest None declared
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