ANA Patterns

AC-12 - Punctate nuclear envelope


Previous Nomenclature	Nuclear membrane pores
Description	Nuclear envelope reveals a punctate staining in interphase cells, with accentuation of fluorescence at the points where adjacent cells touch each other. No staining of the metaphase and anaphase chromatin plates. e.g. anti-gp210.
Antigen Association	nuclear pore complex proteins (i.e. gp210)

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

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Found in patients with PBC, as well as patients with other autoimmune liver diseases and SARD (61)

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If PBC is clinically suspected, it is recommended to perform a follow-up test for anti-gp210 antibodies; the antigen is included in disease specific immunoassays (i.e., extended liver profile*) (62–64)

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Other antigens recognized include p62 nucleoporin, LBR, and Tpr; specific immunoassays for these autoantibodies are currently not commercially available (65-68)

*Availability of the inflammatory myopathy profile, the SSc profile and the (extended) liver profile may be limited to specialty clinical laboratories.

First level information references

61.

Miyachi K, Hankins RW, Matsushima H, et al. Profile and clinical significance of anti-nuclear envelope antibodies found in patients with primary biliary cirrhosis: a multicenter study. J Autoimmun 2003;20:247-54.

62.

Courvalin JC, Lassoued K, Bartnik E, et al. The 210-kD nuclear envelope polypeptide recognized by human autoantibodies in primary biliary cirrhosis is the major glycoprotein of the nuclear pore. J Clin Invest 1990;86:279-85.

63.

Nickowitz RE, Worman HJ. Autoantibodies from patients with primary biliary cirrhosis recognize a restricted region within the cytoplasmic tail of nuclear pore membrane glycoprotein gp210. J Exp Med 1993;178:2237-42.

64.

Bandin O, Courvalin JC, Poupon R, et al. Specificity and sensitivity of gp210 autoantibodies detected using an enzyme-linked immunosorbent assay and a synthetic polypeptide in the diagnosis of primary biliary cirrhosis. Hepatology 1996;23:1020-4.

65.

Wesierska-Gadek J, Klima A, Komina O, et al. Characterization of autoantibodies against components of the nuclear pore complexes: high frequency of anti-p62 nucleoporin antibodies. Ann N Y Acad Sci 2007;1109:519-30.

66.

Kraemer DM, Tony HP. Nuclear pore protein p62 autoantibodies in systemic lupus erythematosus. Open Rheumatol J 2010;4:24-7.

67.

Courvalin JC, Lassoued K, Worman HJ, et al. Identification and characterization of autoantibodies against the nuclear envelope lamin B receptor from patients with primary biliary cirrhosis. J Exp Med 1990;172:961-7.

68.

Ou Y, Enarson P, Rattner JB, et al. The nuclear pore complex protein TPR is a common autoantigen in sera that demonstrate nuclear envelope staining by indirect immunofluorescence. Clin Exp Immunol 2004;136:379-87.

Second level information

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Anti‐p62 nucleoporin antibodies have been described in PBC and SLE (23, 24)

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Anti‐LBR antibodies have been described in PBC (25)

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Anti‐Tpr antibodies have been described in PBC, autoimmune liver disease, SLE, SSc and SjS (26)

Notes: Most reports describe autoantibodies directly binding to specific antigens (i.e., antigen‐specific immunoassays) and do not actually show clear correlations with the AC‐12 pattern as such; specific immunoassays for these autoantibodies are currently not commercially available.

Second level information references

23.

Wesierska-Gadek J, Klima A, Komina O, et al. Characterization of Autoantibodies against Components of the Nuclear Pore Complexes: High Frequency of Anti-p62 Nucleoporin Antibodies. Ann NY Acad Sci 2007;1109:519-30.

24.

Kraemer DM, Tony H-P. Nuclear Pore Protein p62 Autoantibodies in Systemic Lupus Erythematosus. Open Rheumatol J 2010;4:24-7.

25.

Courvalin J-C, Lassoued K, Worman HJ, et al. Identification and Characterization of Autoantibodies Against the Nuclear Envelope Lamin B Receptor from Patients with Primary Biliary Cirrhosis. J Exp Med 1990;172:961-7.

26.

Ou Y, Enarson P, Rattner JB, et al. The nuclear pore complex protein Tpr is a common autoantigen in sera that demonstrate nuclear envelope staining by indirect immunofluorescence. Clin Exp Immunol 2004;136:379-87.

FAQ

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?