OBJECTIVE: To analyze the relationship between the type I interferon (IFN) 
signature and clinical response to rituximab in rheumatoid arthritis (RA) 
patients.
METHODS: Twenty RA patients were treated with rituximab (cohort 1). Clinical 
response was defined as a decrease in the Disease Activity Score evaluated in 28 
joints (DAS28) and as a response according to the European League Against 
Rheumatism (EULAR) criteria at week 12 and week 24. The presence of an IFN 
signature was analyzed in peripheral blood mononuclear cells by measuring the 
expression levels of 3 IFN response genes by quantitative polymerase chain 
reaction analysis. After comparison with the findings in healthy controls, 
patients were classified as having an IFN high or an IFN low signature. The data 
were confirmed in a second independent cohort (n = 31). Serum IFNα bioactivity 
was analyzed using a reporter assay.
RESULTS: In cohort 1, there was a better clinical response to rituximab in the 
IFN low signature group. Consistent with these findings, patients with an IFN 
low signature had a significantly greater reduction in the DAS28 and more often 
achieved a EULAR response at weeks 12 and 24 as compared with the patients with 
an IFN high signature in cohort 2 versus cohort 1. The pooled data showed a 
significantly stronger decrease in the DAS28 in IFN low signature patients at 
weeks 12 and 24 as compared with the IFN high signature group and a more 
frequent EULAR response at week 12. Accordingly, serum IFNα bioactivity at 
baseline was inversely associated with the clinical response, although this 
result did not reach statistical significance.
CONCLUSION: The type I IFN signature negatively predicts the clinical response 
to rituximab treatment in patients with RA. This finding supports the notion 
that IFN signaling plays a role in the immunopathology of RA.