Can a patient with SLE ever be ANA negative?
Yes, but very rarely. Few patients (<1%) with active, untreated SLE will have a negative ANA. These patients usually have one of the following:
• Hereditary early complement component deficiency (C2, C4). These patients usually have low-titer ANAs.
• Have antibodies only to the nuclear antigen SS-A (Ro) and are ANA-negative because:
1. The substrate used in the fluorescent ANA test did not contain sufficient SS-A antigen to allow detection of those antibodies. While such patients are ANA-negative on rodent tissue substrates, they are almost always positive when HEp-2 substrate is used; OR
2. The antibody is only directed against the 52 kDa SS-A/Ro protein, which is located in the cytoplasm and not against the 60 kDa SS-A/Ro protein, which is located in the nucleus.
• A very few cases of SLE may have antibodies restricted to cytoplasmic constituents (e.g., ribosomes, ribosomal P, and others).
• Rarely, SLE patients (up to 10%–15%) will become ANA-negative with treatment and their disease becomes inactive.
• Rarely, SLE patients with severe proteinuria may be ANA-negative due to antibody loss in the proteinuria. ANA becomes positive with decrease in proteinuria with therapy.
• SLE patients with end-stage renal disease on chronic dialysis can become ANA-negative.
• Technical factors and prozone effect can sometimes be responsible for a negative ANA.
