ANA Patterns

AC-13 - PCNA-like


Previous Nomenclature	None
Description	Pleomorphic speckled nucleoplasmic staining is characterized as variability in size and brightness of the speckles. In interphase cells, some cells are negative (G1 phase), some are intensely stained (S-phase) and some demonstrate rare and scattered speckles with occasional nucleolar staining (late S and early G2 phases). M-phase cells are not stained.
Antigen Association	PCNA (proliferating cell nuclear antigen, 35 kDa/elongation factor of DNA polymerase delta auxiliary protein).

Clinical Relevance
First level information
About Clinical Relevance & List of Abbreviations

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The AC-13 pattern was considered highly specific for systemic lupus erythematosus (SLE), but this specificity has been challenged [1, 2]

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If SLE is clinically suspected, it is recommended to perform a follow-up test for PCNA antibodies

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Recent studies with antigen-specific immunoassays show clinical associations with systemic sclerosis, idiopathic inflammatory myopathies, rheumatoid arthritis, hepatitis C viral infection, and other conditions [2-4]

First level information references

Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. J Immunol. 1978;121:2228-34

Vermeersch P, De Beeck KO, Lauwerys BR, Van den Bergh K, Develter M, Marien G, Houssiau FA, Bossuyt X. Antinuclear antibodies directed against proliferating cell nuclear antigen are not specifically associated with systemic lupus erythematosus. Ann Rheum Dis. 2009;68:1791-3

Mahler M, Miyachi K, Peebles C, Fritzler MJ. The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA). Autoimmun Rev. 2012;11:771-5

Hsu TC, Tsay GJ, Chen TY, Liu YC, Tzang BS. Anti-PCNA autoantibodies preferentially recognize C-terminal of PCNA in patients with chronic hepatitis B virus infection. Clin Exp Immunol. 2006;144:110-6

Second level information

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Other nuclear pleomorphic patterns that are distinct from AC-13 should be reported as unclassified patterns (AC-XX) with an appropriate description

Second level information references

None

Last updated in August 2025

FAQ

Anti-PCNA positive by blot and yet negative in HEp-2 IFA?
Can you explain when anti-PCNA antibodies is positive in immunoblot and yet negative in HEp-2 IFA?

Traditional assays for anti-PCNA are double immunodiffusion and HEp-2 IFA. Positive anti-PCNA antibodies as defined by these assays are probably high titer and are associated with SLE. The “new” assays for anti-PCNA using ELISA, Line/Dot blot, CLIA, FEIA, ALBIA, and other solid-phase methods typically detect lower titer (or lower avidity) positives (e.g., higher sensitivity than IFA and immunodiffusion) and this may explain why studies using these methods no longer show a specific association of anti-PCNA with SLE (Vermeersch et al, 2009). More studies are needed on this topic.

A second consideration with anti-PCNA antibodies is that their reactivity has been reported to be highly dependent on the oxidation status of PCNA in the HEp-2 substrate (Tsai et al, 1992). The initial fascinating observation was that if the HEp-2 slide is taken out from the nitrogen-sealed packet at room temperature for 15-30 minutes before starting the first incubation of the diluted serum in the typical IFA protocol, the anti-PCNA staining was negative or substantially reduced while other ANA were not apparently affected. This loss of reactivity to PCNA was apparently due to air oxidation. The report showed that the free thiol group(s) on PCNA is important for anti-PCNA reactivity of samples from SLE patients. Thus, back to the question, the “negative (result) in HEp-2 IFA” would have to be considered more carefully by processing the slide immediately after opening the sealed packet, by using at least one additional HEp-2 slide brand, and by confirming the expected HEp-2 IFA AC-13 pattern with an available reference anti-PCNA serum.

Please note that there have not been any known recent reports that reproduced the data on the oxidation status-dependency of anti-PCNA staining as reported by Tsai et al. ~30 years ago. This is important because HEp-2 substrate processing, stabilization and fixation may have changed since then. In summary, anti-PCNA reactivity in a solid phase assay accompanied by the typical AC-13 pattern may be more specific for SLE compared to a positive reaction in solid phase assays alone.

References
Vermeersch P, De Beeck KO, Lauwerys BR, Van den Bergh K, Develter M, Marien G, Houssiau FA, Bossuyt X (2009) Antinuclear antibodies directed against proliferating cell nuclear antigen are not specifically associated with systemic lupus erythematosus. Ann Rheum Dis 68:1791-1793. DOI: 10.1136/ard.2008.104190

Tsai WM, Roos G, Hugli TE, Tan EM (1992) Influence of free thiol group(s) on autoantibody-defined epitope of proliferating cell nuclear antigen. J Immunol 149:2227-2233.

Mahler M, Miyachi K, Peebles C, Fritzler MJ. The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA). Autoimmun Rev. 2012 Aug;11(10):771-5.

Mahler M, Silverman ED, Fritzler MJ. Novel diagnostic and clinical aspects of anti-PCNA antibodies detected by novel detection methods. Lupus. 2010 Nov;19(13):1527-33.

Date: March 8, 2024