AC-13 - PCNA-like
Previous Nomenclature None
Description Pleomorphic speckled nucleoplasmic staining, with variability in size and brightness of the speckles. In interphase, some cells are negative (G1 phase), some are intensely stained (S-phase) and some present rare and scattered speckles with occasional nucleolar staining (late S and early G2 phases). Mitotic cells are not stained.
Antigen Association PCNA
Clinical Relevance
First level information
About Clinical Relevance & List of Abbreviations

The AC-13 pattern has formerly been considered highly specific for SLE, but this specificity is debated (69, 70)

If SLE is clinically suspected, it is recommended to perform a follow-up test for anti-PCNA antibodies; the antigen is included in several routine ENA profiles (69)

Recent studies with antigen-specific immunoassays show clinical associations also with SSc, AIM, RA, HCV, and other conditions (70–73)

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, et al. 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, Burlingame RW, Wu J, et al. Serological and clinical associations of anti-PCNA antibodies in systemic lupus erythematosus detected by a novel chemiluminescence assay. Arthritis Rheum 2011;63.
Mahler M, Miyachi K, Peebles C, et al. The clinical significance of autoantibodies to the proliferating cell nuclear antigen (PCNA). Autoimmun Rev 2012;11:771-5.
Hsu TC, Tsay GJ, Chen TY, et al. 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

A major challenge in deriving an association of the AC‐13 pattern with antibodies to the classical 35 kDa PCNA (elongation factor of DNA polymerase delta auxiliary protein) is that “PCNA” is known to be a macromolecular complex where targets other than the ‘classical’ 35 kDa PCNA are present. In addition, a number of other apparently unrelated targets can also produce an AC‐13‐like pattern by HEp‐2 IIFA (27)

Second level information references
Takeuchi K, Kaneda K, Kawakami I, et al. Autoantibodies recognizing proteins copurified with PCNA in patients with connective tissue diseases. Mol Biol Rep 1996;23:243-6.

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?

How to deal with just a “nuclear speckled” IFA report?
In my practice I have followed patients with ANA findings, with a nuclear speckled pattern (without specifying whether fine/dense/coarse), in patients with very heterogeneous phenotypes, some with a clinical picture that suggests further investigation of systemic autoimmune disease (one patient with proximal muscle weakness and skin thickening) and others who represent only non-specific findings. In such situations, as a precaution, I request more specific autoantibodies. However, this pattern (nuclear speckled pattern) is not described by the "ICAP" and I am in doubt about which antigenic association it represents, even to guide which autoantibody may be present and which ones to look after. How to interpret this pattern? Does the lab describe it when it is not possible to "refine" such a conclusion? Could this be associated with deficiency in the methodology, sample, interpretation?
Online since 19 May 2015