The present invention relates generally to the generation and characterization of neutralizing anti-IFN-± monoclonal antibodies with broad reactivity against various IFN-± subtypes. The invention further relates to the use of such anti-IFN-± antibodies in the diagnosis and treatment of disorders associated with increased expression of IFN-±, in particular, autoimmune disorders such as insulin-dependant diabetes mellitus (IDDM) and systemic lupus erythematosus (SLE).