B cell depletion in diffuse progressive systemic sclerosis: safety, skin score modification and IL-6 modulation in an up to thirty-six months follow-up open-label trial

Nine patients with SSc with mean age 40.9 ± 11.1 years were treated with anti-CD20, 1 g at time 0 and after 14 days. Skin biopsy was performed at baseline and during the follow-up. B-cell activating factor (BAFF) and IL-6 levels were also determined at the follow-up times.After 6 months patients presented a median decrease of the skin score of 43.3% (range 21.1-64.0%), and a decrease in disease activity index and disease severity index. IL-6 levels decreased permanently during the follow up. After treatment, a complete depletion of peripheral blood B cells was observed in all but 2 patients. Only 3 patients presented CD20 positive cells in the biopsy of the involved skin at baseline.Anti-CD20 treatment has been well tolerated and SSc patients experienced an improvement of the skin score and of clinical symptoms. The clear fall in IL-6 levels could contribute to the skin fibrosis improvement, while the presence of B cells in the skin seems to be irrelevant with respect to the outcome after B cell depletion.ISRCTN77554566.Although the pathogenesis of systemic sclerosis (SSc) remains unknown, the B cell abnormalities characterized by autoantibody production [1], hyper-γ-globulinemia and polyclonal B cell hyperactivity [2] are thought to play an important role in the disease. It has been previously described that SSc patients have distinct abnormalities of blood homeostasis and B cell compartments, characterized by expanded na？ve cells and activated, but diminished, memory B cells [3]. Furthermore, the expression of CD19, a critical signal transduction molecule of B cells that regulates autoantibody production, is significantly increased in memory and na？ve B cells in SSc patients [3,4]. Analysis of DNA microarrays of cutaneous biopsies from diffuse SSc (dSSc) patients demonstrated a higher expression of clusters of genes of CD20-positive cells [5].In the tight-skin mice, a genetic model of human SSc, the CD19 signaling pathway appeared to be constitutively activated [6