ICAP
AC-5 - Nuclear large/coarse speckled
Previous Nomenclature spliceosome/nuclear matrix
Description Coarse speckles across all nucleoplasm. The nucleoli may be stained or not stained. Mitotic cells (metaphase, anaphase, and telophase) have the chromatin mass not stained. e.g. anti-Sm, anti-U1 RNP
Antigen Association hnRNP, U1RNP, Sm, RNA polymerase III
Clinical Relevance
First level information
About Clinical Relevance

Present to a varying degree in distinct SARD, in particular SLE, SSc, MCTD, SSc-AIM overlap syndrome, and UCTD (i.e, patients with rheumatic symptoms without a definite SARD diagnosis) (29)

If SLE is clinically suspected, it is recommended to perform follow-up tests for anti-Sm and anti-U1RNP antibodies; these antigens are commonly included in the routine ENA profile; anti-Sm antibodies are included in the classification criteria for SLE (16, 30, 31)

If SSc is clinically suspected, it is recommended to perform a follow-up test for anti-RNApol III antibodies (e.g., SSc profile*); the anti-RNApol III antibodies are included in the classification criteria for SSc (8)

If MCTD is clinically suspected, it is recommended to perform a follow-up test for anti-U1RNP antibodies; the antigen is commonly included in the routine ENA profile; anti-U1RNP antibodies are included in the diagnostic criteria for MCTD (32)

If the SSc-AIM overlap syndrome is clinically suspected, it is recommended to perform follow-up tests for anti-U1RNP and anti-Ku antibodies; these antigens are included in the routine ENA profile (U1RNP), or in disease specific immunoassays (Ku, i.e., inflammatory myopathy profile* and SSc profile*) (26, 33)

In non-SARD individuals in the general population, the presence of the AC-5 pattern is not associated with the autoantigens mentioned above and most often concerns low antibody titers

*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
8.
van den Hoogen F, Khanna D, Fransen J, et al. 2013 classification criteria for systemic sclerosis: an American College of rheumatology/European League against rheumatism collaborative initiative. Ann Rheum Dis 2013;72:1747–55.
16.
Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the systemic lupus international collaborating clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64:2677–86.
26.
Betteridge Z, McHugh N. Myositis-specific autoantibodies: an important tool to support diagnosis of myositis. J Intern Med 2016;280:8–23.
29.
Northway JD, Tan EM. Differentiation of antinuclear antibodies giving Speckled staining patterns in immunofluorescence. Clin Immunol Immunopathol 1972;1:140–54.
30.
Satoh M, Fritzler MJ, Chan EKL. Antihistone and antispliceosomal antibodies. In: Lahita RG, Tsokos G, Buyon JP, et al, eds. Systemic lupus erythematosus. San Diego: Academic Press, 2011: 275–92.
31.
Satoh M, Vázquez-Del Mercado M, Chan EK. Clinical interpretation of antinuclear antibody tests in systemic rheumatic diseases. Mod Rheumatol 2009;19:219–28.
32.
Sharp GC, Irvin WS, Tan EM, et al. Mixed connective tissue disease--an apparently distinct rheumatic disease syndrome associated with a specific antibody to an extractable nuclear antigen (ENA). Am J Med 1972;52:148–59.
Second level information

Occasionally, autoantibodies revealing the AC‐5 pattern are reactive with RNP other than U1RNP, for instance U2RNP (associated with SSc‐AIM overlap syndrome) or U11/U12RNP (associated with SSc); these autoantibodies can be detected by immunoprecipitation (13, 14).

 

Note: Specific immunoassays for these autoantibodies are currently not commercially available.

Second level information references
13.
Mimori T, Hinterberger M, Pettersson I, et al. Autoantibodies to the U2 small nuclear ribonucleoprotein in a patient with scleroderma‐polymyositis overlap syndrome. J Biol Chem 1984;259:560‐5.
14.
Fretig N, Domsic RT, Rodriguez‐Reyna T, et al. Anti‐U11/U12 RNP antibodies in systemic sclerosis: a new serologic marker associated with pulmonary fibrosis. Arthritis Rheum 2009;61:958‐65.
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Online since 19 May 2015