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Aim of the work: This study was conducted to compare the HLA-DQB1*06 allele frequency among Egyptian SLE patients and controls. The association of that allele with clinical features and distinct autoantibody profiles in SLE patients was also assessed.Patients and methods: This study included 48 consecutive Egyptian SLE patients and 49 age and sex matched unrelated healthy Egyptian subjects as a control group. All patients underwent full history taking, thorough clinical examination, SLE cumulative organ damage was scored using the Systemic Lupus International Collaborating Clinics (SLICC) damage index. Routine laboratory investigations were done as well Genomic DNA amplification by polymerase chain reaction with sequence-specific primers technique (PCR-SSP) to detect HLA DQB1*6.Results: HLA-DQB1*06 was significantly more frequent among the SLE patients. Our results showed HLA-DQB1*06 to be associated with SLE (39.6% in patients and 8.2% in controls, OR = 7.23; 95% CI = 2.22-23.6; P = .00). We found no association with the clinical findings or antibodies found in our patients apart from a significant negative association with vasculitis.