Abstract: Methods for detecting an autoimmune disease or a high risk of developing an autoimmune disease in a subject are provided. In a first aspect, a sample from the subject for a haplotype of IRF5 is assayed. The sample is further assayed for a HLA risk allele pair. It is then detected whether the subject has an autoimmune disease or is at high risk for an autoimmune disease when a haplotype of IRF5 and a HLA risk allele pair are present in the sample. The autoimmune disease can be lupus erythematosus (SLE), Sjögren's syndrome (SS), or other autoimmune diseases.