OBJECTIVE: B cells impact the progression of systemic sclerosis (SSc; 
scleroderma) through multiple pathogenic mechanisms. CD19 inhibition in mice 
reduced skin thickness, collagen production, and autoantibody levels, consistent 
with CD19 expression on plasma cells (PCs), the source of antibody production. 
PC depletion could effectively reduce collagen deposition and inflammation in 
SSc; therefore, we investigated the effects of PC depletion on SSc disease 
activity.
METHODS: A PC gene signature was evaluated in SSc skin biopsy samples in 2 phase 
I clinical trials. We assessed microarray data from tissue from public studies 
of chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis 
(IPF), dermatomyositis (DM), systemic lupus erythematosus (SLE), and atopic 
dermatitis, as well as blood from a phase IIb clinical trial in SLE.
RESULTS: The PC signature was elevated in SSc skin specimens compared to healthy 
donor skin (P = 2.28 × 10-6 ) and correlated with the baseline modified Rodnan 
skin thickness score (MRSS) (r = 0.64, P = 0.0004). Patients with a high PC 
signature at baseline showed greater improvement in the MRSS (mean ± SD change 
35 ± 16%; P = 6.30 × 10-4 ) following anti-CD19 treatment with inebilizumab 
(MEDI-551) than did patients with a low PC signature at baseline (mean ± SD 
change 8 ± 12%; P = 0.104). The PC signature was overexpressed in tissue from 
patients with SLE, DM, COPD, interstitial lung disease, and IPF relative to 
controls (all fold change >2; P < 0.001). The PC signature also differed 
significantly between SLE patients with mild-to-moderate disease and those with 
severe disease (SLE Disease Activity Index cutoff at 10) (fold change 1.44; P = 
3.90 × 10-3 ) and correlated significantly with the degree of emphysema in COPD 
(r = 0.53, P = 7.55 × 10-8 ).
CONCLUSION: Our results support the notion that PCs have a role in the 
pathogenesis of SSc and other autoimmune or pulmonary indications. An elevated 
pretreatment PC signature was associated with increased benefit from MEDI-551 in 
SSc.