The invention provides methods and compositions for treating various autoimmune diseases (such as systemic lupus erythematousu) with an interferon inhibitor (such as an anti-intereron-alpha monoclonal antibody). More specifically, the invention provides a method of diagnosing, monitoring and adjusting the treatment of such a patient by way of an interferon signature metric (interferon response gene measurement value), a certain anti-dsDNA antibody titre or being ENA- (levels of extractable nuclear antigens lower than a healthy level). Furthermore, the invention provides articles of manufacture associated with such a diagnosis.