Objectives: A proliferation-inducing ligand (APRIL) plays a crucial role in survival of the peripheral B cells, and may contribute to the pathogenesis of systemic sclerosis (SSc) through upregulation of autoantibody production and maintenance of the autoimmune phenomenon. It has recently been shown that peripheral blood mononuclear cells (PBMC) from patients with SSc release significantly greater amounts of APRIL as compared with healthy controls (HC).
Aim of the study: To better understand the role of APRIL in the development of SSc we aimed to investigate the relationships between production of APRIL by PBMC and clinical outcome in patients with SSc.
Material and methods: Concentration of APRIL was measured in PBMC supernatants from 22 SSc patients and 17 healthy subjects using commercially available ELISA kits. SSc patients were subsequently followed for at least three years or until death, whichever happened earlier. Disease progression was defined as death due to SSc-related organ complication, development of a new or progression of pre-existing SSc-related organ involvement.
Results: Concentration of APRIL was significantly greater in supernatants of PBMC from SSc (1097 ±240 pg/ml/105) as compared with HC (851 ±171 pg/ml/105, p < 0.05). In SSc patients APRIL levels correlated with the severity of skin and lung involvement. PBMC from 7 patients who experienced progression of the disease released significantly greater amounts of APRIL (1326 ±105 pg/ml/105 cells) as compared with those SSc patients with stable disease (991 ±208 pg/ml/105 cells, p < 0.05) and HC. In regression analysis concentration of APRIL was independently associated with disease outcome (β coeff = –0.94, p = 0.0009).
Conclusions: We show for the first time that increased release of APRIL by PBMC is associated with worse disease outcome in SSc. Further studies are needed to investigate whether targeting APRIL might represent a new therapeutic possibility for treatment of SSc patients.