CENP-A stands for centromere proteins A.
Centromere antibodies can be directed against a number of centromere proteins (CENP), including CENP-A, -B, and -C, though CENP-B is thought to be the main target.
These antibodies are found in 20% to 40% of patients with SSc and are associated with the lcSSc subtype.
Furthermore, centromere antibodies are included in the 2013 ACR-EULAR classification criteria. However, these antibodies can occur in other connective tissue diseases, including:
- systemic lupus erythematosus (SLE),
- primary biliary cholangitis,
- rheumatoid arthritis,
- and Sjögren syndrome.
Presence of centromere antibodies is considered predictive of SSc development in patients with Raynaud phenomenon (a problem that causes decreased blood flow to the fingers. In some cases, it also causes less blood flow to the ears, toes, nipples, knees, or nose. This happens due to spasms of blood vessels in those areas. The spasms happen in response to cold, stress, or emotional upset.)
The antibodies are associated with lower risk of cardiac and renal involvement but higher risk of PAH (= pulmonary arterial hypertension). For patients without PAH, centromere antibodies are associated with a better prognosis overall than are other autoantibodies.
Systemic Sclerosis Classification Criteria:
|
Classify as having systemic sclerosis if the sum of points for criteria below is ≥9. |
|
|
Criterion |
Points |
|
Skin thickened on fingers of both hands, extending proximal to the metacarpophalangeal joints |
9 |
|
Skin on fingers thickened (only count highest score) Puffy fingers Sclerodactylya |
2 4 |
|
Lesions on fingertips (only count highest score) Ulcers on tip of digits Pitting scars on fingertips |
2 3 |
|
Telangiectasia |
2 |
|
Abnormal nailfold capillaries |
2 |
|
Pulmonary arterial hypertension and/or interstitial lung disease (max score is 2) Pulmonary arterial hypertension Interstitial lung disease |
2 2 |
|
Raynaud phenomenon |
3 |
|
Presence of 1 or more of the following: Centromere antibody Scl-70 antibody RNA polymerase III antibody |
3 |
Clinical Characteristics Associated With Autoantibodies Used in the Diagnosis and Classification of Systemic Sclerosisa:
|
Antibody |
Prevalence in SSc, % |
Presence in other autoimmune diseases |
SSc type most likely |
Clinical associations |
Relative SSc prognosis |
|
ANA |
85-95 |
Common |
Does not help differentiate type |
Most common in rheumatic diseases |
Varies |
|
Centromere A or B |
20-40 b |
Uncommon |
lcSSc |
PAH, calcinosis, digital ischemia, intestinal involvement |
Better |
|
Ku |
1.5-5 |
Common |
Overlap syndromes or lcSSc |
Muscle and joint involvement |
Unclear |
|
PM/Scl-75 or PM/Scl-100 |
2-11 |
Common |
SSc-myositis overlap syndrome or lcSSc |
Muscle and joint involvement, calcinosis; GI and lung involvement for those with PM/Scl-75 |
Better |
|
RNA Polymerase III |
7-41 |
Rare |
dcSSc |
Renal crisis, progressive skin thickening, GAVE, malignancy |
Poorer |
|
Scl-70 |
9.4-71 b |
Rare |
dcSSc |
Severe pulmonary fibrosis, cardiac involvement, renal crisis, digital ulcers |
Poorer |
|
Th/To |
2-5 |
Rare |
lcSSc |
Pulmonary involvement |
Poorer |
|
U1-snRNP |
2-14 |
Common (90% in patients with MCTD) |
lcSSc |
PAH, arthritis, esophageal dysfunction |
Better |
|
U3-RNP (Fibrillarin) |
4-10 b |
Rare |
dcSSc |
Multiorgan involvement, PAH |
Poorer |
| ANA, antinuclear antibodies; dcSSc, diffuse cutaneous systemic sclerosis; GAVE, gastric antral vascular ectasia; GI, gastrointestinal; lcSSc, limited cutaneous systemic sclerosis; MCTD, mixed connective tissue disease; PAH, pulmonary arterial hypertension; SSc, systemic sclerosis. | |
| a | Data presented in this table have been compiled from the cited references. It is important to note that autoantibody frequency in SSc as well as other autoimmune diseases varies with sex, ethnicity, and population studied. |
| b | In the United States, prevalence has been shown to vary across ethnicities. |
References:
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. Arthritis Rheum. 2013;65(11):2737-2747. doi:10.1002/art.38098
Stochmal A, Czuwara J, Trojanowska M, et al. Antinuclear antibodies in systemic sclerosis: an update. Clin Rev Allergy Immunol. 2020;58(1):40-51. doi:10.1007/s12016-018-8718-8
Kayser C, Fritzler MJ. Autoantibodies in systemic sclerosis: unanswered questions. Front Immunol. 2015;6:167. doi:10.3389/fimmu.2015.00167
Hamaguchi Y, Takehara K. Anti-nuclear autoantibodies in systemic sclerosis: news and perspectives. J Scleroderma Relat Disord. 2018;3(3):201-213. doi:10.1177/2397198318783930
Mahler M, Meroni PL, Bossuyt X, et al. Current concepts and future directions for the assessment of autoantibodies to cellular antigens referred to as anti-nuclear antibodies. J Immunol Res. 2014;2014:315179. doi:10.1155/2014/315179
Cavazzana I, Fredi M, Taraborelli M, et al. A subset of systemic sclerosis but not of systemic lupus erythematosus is defined by isolated anti-Ku autoantibodies. Clin Exp Rheumatol. 2013;31(2 suppl 76):118-121.
D'Aoust J, Hudson M, Tatibouet S, et al. Clinical and serologic correlates of anti-PM/Scl antibodies in systemic sclerosis: a multicenter study of 763 patients. Arthritis Rheumatol. 2014;66(6):1608-1615. doi:10.1002/art.38428
Wodkowski M, Hudson M, Proudman S, et al. Clinical correlates of monospecific anti-PM75 and anti-PM100 antibodies in a tri-nation cohort of 1574 systemic sclerosis subjects. Autoimmunity. 2015;48(8):542-551. doi:10.3109/08916934.2015.1077231
Shah AA, Hummers LK, Casciola-Rosen L, et al. Examination of autoantibody status and clinical features associated with cancer risk and cancer-associated scleroderma. Arthritis Rheumatol. 2015;67(4):1053-1061. doi:10.1002/art.39022
Sobanski V, Dauchet L, Lefèvre G, et al. Prevalence of anti-RNA polymerase III antibodies in systemic sclerosis: new data from a French cohort and a systematic review and meta-analysis. Arthritis Rheumatol. 2014;66(2):407-417. doi:10.1002/art.38219
Pokeerbux MR, Giovannelli J, Dauchet L, et al. Survival and prognosis factors in systemic sclerosis: data of a French multicenter cohort, systematic review, and meta-analysis of the literature. Arthritis Res Ther. 2019;21(1):86. doi:10.1186/s13075-019-1867-1
Mehra S, Walker J, Patterson K, et al. Autoantibodies in systemic sclerosis. Autoimmun Rev. 2013;12(3):340-354. doi:10.1016/j.autrev.2012.05.011
Krzyszczak ME, Li Y, Ross SJ, et al. Gender and ethnicity differences in the prevalence of scleroderma-related autoantibodies. Clin Rheumatol. 2011;30(10):1333-1339. doi:10.1007/s10067-011-1751-0
Nandiwada SL, Peterson LK, Mayes MD, et al. Ethnic differences in autoantibody diversity and hierarchy: more clues from a US cohort of patients with systemic sclerosis. J Rheumatol. 2016;43(10):1816-1824. doi:10.3899/jrheum.160106
Federico Perosa, Marcella Prete, Giuseppe Di Lernia, Carmela Ostuni, Elvira Favoino, Gabriele Valentini, Anti-centromere protein A antibodies in systemic sclerosis: Significance and origin, Autoimmunity Reviews, Volume 15, Issue 1, 2016, Pages 102-109, ISSN 1568-9972, https://doi.org/10.1016/j.autrev.2015.10.001.
Systemic sclerosis (SSc) is systemic, autoimmune, connective tissue disorder characterized by vascular abnormalities, collagen deposition (fibrosis), and the production of autoantibodies to nuclear proteins. About 20%–40% of patients have antibodies to centromere protein (CENP)-A or -B.
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Optimal Result:
0 - 11 SI.