Clinical and serological evaluation of a novel CENP-A peptide based ELISA
- PMID: 20487535
- PMCID: PMC2911886
- DOI: 10.1186/ar3029
Clinical and serological evaluation of a novel CENP-A peptide based ELISA
Abstract
Introduction: Anti-centromere antibodies (ACA) are useful biomarkers in the diagnosis of systemic sclerosis (SSc). ACA are found in 20 to 40% of SSc patients and, albeit with lower prevalence, in patients with other systemic autoimmune rheumatic diseases. Historically, ACA were detected by indirect immunofluorescence (IIF) on HEp-2 cells and confirmed by immunoassays using recombinant CENP-B. The objective of this study was to evaluate a novel CENP-A peptide ELISA.
Methods: Sera collected from SSc patients (n=334) and various other diseases (n=619) and from healthy controls (n=175) were tested for anti-CENP-A antibodies by the novel CENP-A enzyme linked immunosorbent assay (ELISA). Furthermore, ACA were determined in the disease cohorts by IIF (ImmunoConcepts, Sacramento, CA, USA), CENP-B ELISA (Dr. Fooke), EliA CENP (Phadia, Freiburg, Germany) and line-immunoassay (LIA, Mikrogen, Neuried, Germany). Serological and clinical associations of anti-CENP-A with other autoantibodies were conducted in one participating centre. Inhibition experiments with either the CENP-A peptide or recombinant CENP-B were carried out to analyse the specificity of anti-CENP-A and -B antibodies.
Results: The CENP-A ELISA results were in good agreement with other ACA detection methods. According to the kappa method, the qualitative agreements were: 0.73 (vs. IIF), 0.81 (vs. LIA), 0.86 (vs. CENP-B ELISA) and 0.97 (vs. EliA CENP). The quantitative comparison between CENP-A and CENP-B ELISA using 265 samples revealed a correlation value of rho=0.5 (by Spearman equation). The receiver operating characteristic analysis indicated that the discrimination between SSc patients (n=131) and various controls (n=134) was significantly better using the CENP-A as compared to CENP-B ELISA (P<0.0001). Modified Rodnan skin score was significantly lower in the CENP-A negative group compared to the positive patients (P=0.013). Inhibition experiments revealed no significant cross reactivity of anti-CENP-A and anti-CENP-B antibodies. Statistically relevant differences for gender ratio (P=0.0103), specific joint involvement (Jaccoud) (P=0.0006) and anti-phospholipid syndrome (P=0.0157) between ACA positive SLE patients and the entire SLE cohort were observed.
Conclusions: Anti-CENP-A antibodies as determined by peptide ELISA represent a sensitive, specific and independent marker for the detection of ACA and are useful biomarkers for the diagnosis of SSc. Our data suggest that anti-CENP-A antibodies are a more specific biomarker for SSc than antibodies to CENP-B. Furthers studies are required to verify these findings.
Figures



Similar articles
-
Anti-centromere antibodies in a large cohort of systemic sclerosis patients: comparison between immunofluorescence, CENP-A and CENP-B ELISA.Clin Chim Acta. 2011 Oct 9;412(21-22):1937-43. doi: 10.1016/j.cca.2011.06.041. Epub 2011 Jul 5. Clin Chim Acta. 2011. PMID: 21756890
-
Anti-CENP-B response in sera of uranium miners exposed to quartz dust and patients with possible development of systemic sclerosis (scleroderma).J Rheumatol. 1995 Jul;22(7):1286-94. J Rheumatol. 1995. PMID: 7562760
-
Clinical correlates of a subset of anti-CENP-A antibodies cross-reacting with FOXE3p53-62 in systemic sclerosis.Arthritis Res Ther. 2013 Jul 9;15(4):R72. doi: 10.1186/ar4249. Arthritis Res Ther. 2013. PMID: 23837651 Free PMC article.
-
Anti-centromere protein A antibodies in systemic sclerosis: Significance and origin.Autoimmun Rev. 2016 Jan;15(1):102-9. doi: 10.1016/j.autrev.2015.10.001. Epub 2015 Oct 9. Autoimmun Rev. 2016. PMID: 26455561 Review.
-
Diagnostic accuracy and predictive value of extended autoantibody profile in systemic sclerosis.Autoimmun Rev. 2012 Dec;12(2):114-20. doi: 10.1016/j.autrev.2012.07.005. Epub 2012 Jul 7. Autoimmun Rev. 2012. PMID: 22776784 Review.
Cited by
-
Pathogenic role of anti-nuclear autoantibodies in systemic sclerosis: Insights from other rheumatic diseases.Immunol Rev. 2024 Nov;328(1):265-282. doi: 10.1111/imr.13390. Epub 2024 Sep 9. Immunol Rev. 2024. PMID: 39248128 Free PMC article. Review.
-
Autoantibodies recognizing the amino terminal 1-17 segment of CENP-A display unique specificities in systemic sclerosis.PLoS One. 2013 Apr 22;8(4):e61453. doi: 10.1371/journal.pone.0061453. Print 2013. PLoS One. 2013. PMID: 23613856 Free PMC article.
-
A novel peptide ELISA for universal detection of antibodies to human H5N1 influenza viruses.PLoS One. 2011;6(6):e20737. doi: 10.1371/journal.pone.0020737. Epub 2011 Jun 10. PLoS One. 2011. PMID: 21695200 Free PMC article.
-
Rpp25 is a major target of autoantibodies to the Th/To complex as measured by a novel chemiluminescent assay.Arthritis Res Ther. 2013 Apr 12;15(2):R50. doi: 10.1186/ar4210. Arthritis Res Ther. 2013. PMID: 23587095 Free PMC article.
-
Classical Disease-Specific Autoantibodies in Systemic Sclerosis: Clinical Features, Gene Susceptibility, and Disease Stratification.Front Med (Lausanne). 2020 Nov 19;7:587773. doi: 10.3389/fmed.2020.587773. eCollection 2020. Front Med (Lausanne). 2020. PMID: 33330547 Free PMC article. Review.
References
-
- Miyawaki S, Asanuma H, Nishiyama S, Yoshinaga Y. Clinical and serological heterogeneity in patients with anticentromere antibodies. J Rheumatol. 2005;32:1488–1494. - PubMed
-
- Tojo J, Ohira H, Suzuki T, Takeda I, Shoji I, Kojima T, Takagi T, Kuroda M, Miyata M, Nishimaki T, Ohnami K, Kanno T, Mukai S, Kasukawa R. Clinicolaboratory characteristics of patients with primary biliary cirrhosis associated with CREST symptoms. Hepatol Res. 2002;22:187–195. doi: 10.1016/S1386-6346(01)00138-3. - DOI - PubMed
-
- Assassi S, Fritzler MJ, Arnett FC, Norman GL, Shah KR, Gourh P, Manek N, Perry M, Ganesh D, Rahbar MH, Mayes MD. Primary biliary cirrhosis (PBC), PBC autoantibodies, and hepatic parameter abnormalities in a large population of systemic sclerosis patients. J Rheumatol. 2009;36:2250–2256. doi: 10.3899/jrheum.090340. - DOI - PMC - PubMed
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical