Clinical Significance of PCNA-Positive ANA
Anti-PCNA antibodies are rare (found in only 2-5% of SLE patients) but when present, they are highly specific for systemic lupus erythematosus and correlate with severe disease manifestations, particularly renal and central nervous system involvement. 1, 2
Understanding PCNA and Its Detection
PCNA (proliferating cell nuclear antigen) is a 33-34 kDa protein that functions as part of the DNA polymerase delta complex and is expressed predominantly during the late G1 and S phases of the cell cycle. 1, 3
The PCNA-like immunofluorescence pattern is extremely rare, occurring in only 0.07% (2 out of 2,500) of unselected sera submitted for autoantibody testing. 4
Indirect immunofluorescence is not an accurate screening method for anti-PCNA antibodies because their presence may be masked by other autoantibodies—specific immunoassays (ELISA, line immunoassay, or addressable laser bead assay) are required for reliable detection. 4
Disease Associations and Clinical Significance
While anti-PCNA antibodies were historically considered specific for SLE, more recent studies have found the highest prevalence in Sjögren's syndrome (5.0%), challenging the exclusive SLE association. 4
In SLE patients who are anti-PCNA positive, there is a high frequency of severe organ involvement including renal disease, central nervous system manifestations, and thrombocytopenia. 2
Anti-PCNA antibodies are frequently accompanied by anti-Ro52 antibodies when detected by immunofluorescence and immunoblot methods. 4
Clinical Management Algorithm
When anti-PCNA antibodies are detected:
Order comprehensive SLE-specific testing including anti-dsDNA (both CLIFT and solid-phase assay), complete ENA panel (anti-Sm, anti-RNP, anti-SSA/Ro, anti-SSB/La), complement levels (C3, C4), and complete blood count to assess for cytopenias. 5, 6
Perform urinalysis with protein/creatinine ratio to screen for lupus nephritis, as anti-PCNA positivity correlates with renal involvement. 5, 2
Evaluate for neurologic symptoms given the association with CNS lupus—consider neurologic examination and imaging if any symptoms are present. 2
Monitor anti-PCNA antibody titers during treatment, as titers may become elevated before the development of proteinuria and decrease with corticosteroid therapy, making them useful for disease activity monitoring. 2
Critical Pitfalls to Avoid
Do not rely on immunofluorescence pattern alone to identify anti-PCNA antibodies—at cut-off values with 100% specificity, only 35-52.5% of samples with PCNA-like staining patterns are confirmed positive by specific immunoassays. 4
Do not assume anti-PCNA is exclusively associated with SLE—consider Sjögren's syndrome and other autoimmune conditions in the differential diagnosis, particularly when other disease-specific antibodies are present. 4
Recognize that the rarity of anti-PCNA positivity (0.07% prevalence) means most positive ANA results are due to other autoantibodies—always pursue comprehensive specific antibody testing rather than assuming PCNA positivity based on pattern alone. 4
In patients with high clinical suspicion for SLE or Sjögren's syndrome, request specific anti-PCNA testing by ELISA or other solid-phase assays regardless of the immunofluorescence pattern, as some autoantibodies may be present despite negative or atypical ANA patterns. 5, 4