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Systemic lupus erythematosus (SLE) is an autoimmune connective disorder characterized by the presence of autoantibodies. Indirect immunofluorescence is considered as the gold standard for the detection of antinuclear antibodies (ANA). False-negative ANA results have resulted in misclassification of some patients as ANA-negative SLE. There are many possible explanations for this negative ANA status of SLE patients. Current evidence in literature suggests that ANA-negative lupus is a questionable entity.