ICAP
AC-3 - Centromere
Previous Nomenclature Kinetochore
Description Discrete coarse speckles (40-80/cell) scattered in interphase cells and aligned at the chromatin mass on mitotic cells. e.g. anti-CENP-B
Antigen Association CENP-A/B (C)
Clinical Relevance
First level information
About Clinical Relevance

Commonly found in patients with limited cutaneous SSc, and as such included in the classification criteria for SSc (8, 15, 23)

In combination with Raynaud phenomenon, the AC-3 pattern is predictive for onset of limited cutaneous SSc (15, 23)

Strongly associated with antibodies to CENP-B; the CENP-B antigen is included in many routine multi-analyte solid phase immunoassay profiles (15); especially in case of low titers, confirmation by an antigen-specific solid phase immunoassay is recommended;

The AC-3 pattern is also observed in a subset of patients with PBC; these patients often have both SSc as well as PBC (15)

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.
15.
Conrad K, Schössler W, Hiepe F. Autoantibodies in systemic autoimmune diseases: a diagnostic reference. 2. 3th edn. Autoantigens autoantibodies autoimmunity, 2015.
23.
Johnson SR, Fransen J, Khanna D, et al. Validation of potential classification criteria for systemic sclerosis. Arthritis Care Res 2012;64:358-67
Second level information

The AC-3 pattern is reported in a subset of patients with SjS; these patients show mild SSc features, but a full-blown SjS clinical feature, more severe exocrine glandular dysfunction, and high risk of lymphoma (1-4)

The AC-3 pattern is also reported in a subset of patients with SLE; these patients often have some degree of overlap with SSc (5)

Most sera with the AC-3 pattern react with CENP-A and CENP-B; antibodies to CENP-A can be detected in some disease specific solid phase immunoassays (i.e., SSc profile) (6, 7)

In rare cases AC-3 positive, but CENP-B negative sera of SSc patients may be strongly positive for anti-CENP-A antibodies (8, 9)

Antibodies to CENP-C have been reported in patients with SSc and SjS (10-12)

 
Note: Availability of assays for CENP-A, (i.e., ELISA or SSc profile) may be limited to specialty clinical laboratories; specific immunoassays for anti-CENP-C antibodies are currently not commercially available.
Second level information references
1.
Vasiliki-Kallipi KB, Diamanti KD, Vlachoyiannopoulos PG, et al. Anticentromere antibody positive Sjögren’s Syndrome: a retrospective descriptive analysis. Arthritis Res Ther 2010;12:R47.
2.
Lee KE, Kang JH, Lee JW, et al. Anti-centromere antibody-positive Sjögren’s syndrome: a distinct clinical subgroup? Int J Rheum Dis 2015;18:776-82.
3.
Baldini C, Mosca M, Della Rossa A, et al. Overlap of ACA-positive systemic sclerosis and Sjögren’s syndrome: a distinct clinical entity with mild organ involvement but a high risk of lymphoma. Clin Exp Rheumatol 2013;31:272-80.
4.
Baer AN, Medrano L, McAdams-Demarco M, et al. Association of anticentromere antibodies with more severe exocrine glandular dysfunction in Sjögren’s syndrome: analysis of the Sjögren’s International Collaborative Clinical Alliance Cohort. Arthritis Care Res 2016;68:1554-9.
5.
Nakano M, Ohuchi Y, Hasegawa H, et al. Clinical significance of anticentromere antibodies in patients with systemic lupus erythematosus. J Rheumatol 2000;27:1403-7.
6.
Perosa F, Prete M, Di Lernia G, et al. Anti-centromere protein A antibodies in systemic sclerosis: significance and origin. Autoimmun Rev 2016;15:102-9.
7.
Mahler M, Maes L, Blockmans D, et al. Clinical and serological evaluation of a novel CENP-A peptide based ELISA. Arthritis Res Ther 2010;12:R99.
8.
Russo K, Hoch S, Varga J, et al. Circulating anticentromere CENP-A and CENP-B antibodies in patients with diffuese and limited systemic sclerosis, systemic lupus erythematosis, and rheumatoid arthritis. J Rheumatol 2000;27:142-8.
9.
Hudson M, Mahler M, Pope J, et al. Clinical correlates of CENP-A and CENP-B antibodies in a large cohort of patients with systemic sclerosis. J Rheumatol 2012;39:787-94.
10.
Pillemer SR, Casciola-Rosen L, Baum BJ, et al. Centromere protein C is a target of autoantibodies in Sjogren's syndrome and is uniformly associated with antibodies to Ro and La. J Rheumatol 2004;31:1121-5.
11.
Gelber AC, Pillemer SR, Baum BJ, et al. Distinct recognition of antibodies to centromere proteins in primary Sjogren's syndrome compared with limited scleroderma. Ann Rheum Dis 2006;65:1028-32.
FAQ
No FAQ received
 
 
Online since 19 May 2015