AC-8 - Homogeneous Nucleolar

Diffuse fluorescence of the entire nucleolus, while the metaphase plate shows no staining. e.g. anti-PM-Scl, anti-Th/To.
Associação Antigênica
PM/Scl-75, PM/Scl-100, Th/To, B23/nucleophosmin, nucleolin, No55/SC65
Doença Associada
SSc, SSc/PM overlap
Relevância Clínica (Primeiro Nível)
Found in patients with SSc, SSc-AIM overlap syndrome, and patients with clinical manifestations of other SARD.
If limited cutaneous SSc is clinically suspected, it is recommended to perform a follow-up test for anti-Th/ To antibodies; the antigen is included in disease specific immunoassays (ie, SSc profile).
If SSc-AIM overlap syndrome is clinically suspected, it is recommended to perform a follow-up test for anti-PM/Scl antibody reactivity; the antigen may be included in the routine ENA profile and is included in disease specific immunoassays (i.e., inflammatory myopathy profile* and the SSc profile); in general, anti- PM/Scl antibodies yield a diffuse nuclear fine speckled staining in addition to the AC-8 pattern.
Other antigens recognized include B23/nucleophosmin, No55/SC65, and C23/nucleolin, but the clinical significance of these autoantibodies is not well established; specific immunoassays for these autoantibodies are currently not commercially available.
Although some anti-Th/To antibody immunoassays are commercially available, technical issues relating to the limited sensitivity of these immunoassays should be taken in to consideration.
Relevância Clínica (Segundo Nível)
The AC-8 pattern that is the result of the anti-Th/To reactivity is also seen in patients with SLE, UCTD (i.e., patients with rheumatic symptoms without a SARD diagnosis), SSc sine scleroderma, idiopathic interstitial lung disease or pulmonary hypertension.
Patients with autoantibodies revealing the AC-8 pattern due to anti-PM/Scl reactivity may have, in addition to the clinical features of AIM and SSc, various clinical manifestations of SLE and SjS.
Ceribelli A, Cavazzana I, Franceschini F, et al. Anti-Th/To are common antinucleolar autoantibodies in Italian patients with scleroderma. J Rheumatol 2010;37:2071–5.

Fischer A, Meehan RT, Feghali-Bostwick CA, et al. Unique characteristics of systemic sclerosis sine scleroderma-associated interstitial lung disease. Chest 2006;130:976-981.

Fischer A, Pfalzgraf FJ, Feghali-Bostwick CA, et al. Anti-Th/To-Positivity in a Cohort of Patients with Idiopathic Pulmonary Fibrosis. J Rheumatol 2006;33:1600-1605.

Mahler M, Fritzler MJ, Satoh M. Autoantibodies to the mitochondrial RNA processing (MRP) complex also known as Th/To autoantigen. Autoimmun Rev 2015;14:254–7.
Mahler M, Raijmakers R. Novel aspects of autoantibodies to the PM/Scl complex: clinical, genetic and diagnostic insights. Autoimmun Rev 2007;6:432–7.

Mahler M, Gascon C, Patel S, et al. Rpp25 is a major target of autoantibodies to the Th/To complex as measured by a novel chemiluminescent assay. Arthritis Res Ther 2013;15.