A rare HLA DQB allele sequenced from patients with systemic lupus erythematosus

Most autoimmune disorders are associated with particular alleles of the major histocompatibility complex (MHC) class II genes. However, only a minority of individuals with these alleles develop autoimmunity. The identification of alleles more closely associated with an autoimmune disorder such as lupus would facilitate screening and diagnosis and perhaps the understanding of mechanisms of disease. Analysis of sequence variation in the polymorphic first domain of the MHC genes HLA DQBβ and DQα has revealed a novel DQβ allele in two Caucasian lupus patients and no Caucasian controls. The novel DQβ allele shares polymorphic amino acids at positions 26 to 30 and 57 with other lupus-associated DQβ alleles. These hyper-variable regions may play a role in lupus susceptibility and may provide insights into the molecular mechanism for this susceptibility.