BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease caused by genetic and environmental factors such as viral infections. Genomic and serologic tests were applied to detect significant blood-borne viruses in SLE patients to determine whether there was a possible association between viral infections and SLE. MethodsAntibodies (Abs) against HHV-8, HCMV, EBV, HIV, HBV, and HCV in SLE patients suffering from SLE were assessed by ELISA. In addition, HHV-8 DNA and HIV-1 RNA were quantified by real-time PCR, and the HCV and HBV genomes were detected using nested PCR. ResultsCompared to those in the control group, a high prevalence of anti-HHV-8 (p < 0.0001), anti-HCMV (p = 0.014), and anti-EBV (p = 0.017) Abs was detected in SLE patients. HHV-8, HIV, HCV, and HBV genomic tests were negative in both groups, while only 1.1 %, 2.2 %, and 1.1 % of SLE patients were positive for anti-HIV, anti-HCV Abs, and HBsAg, respectively. The most frequent major complaint in patients was arthralgia (76.7 %). ConclusionsThe increased prevalence of anti-HHV-8 Abs may not be related to the natural history of infection but to molecular mimicry. Increased anti-HCMV and anti-EBV Abs may also be associated with the development of SLE and may play direct or indirect roles in such infections or molecular mimicry. Since arthralgia is the most common symptom in SLE patients, the presence of these symptoms in any patient is a suggestive clue for the diagnosis of SLE. Defining the typical pattern of SLE in divergent nations with distinct environmental and geographical factors can be beneficial for obtaining a prompt diagnosis.