Related Experiment Video
Updated: Aug 12, 2026
Anti-Nuclear Antibody Screening Using HEp-2 Cells
Published on: June 24, 2014
Clinical and serological heterogeneity in patients with anticentromere antibodies
Shoji Miyawaki1, Hiroko Asanuma, Susumu Nishiyama
1Rheumatic Diseases Center, Kurashiki Medical Center, Okayama, Japan. smutakata@muh.biglobe.ne.jp
Insights
Anticentromere antibodies (ACA) are primarily found in systemic sclerosis (SSc) patients with CREST features. High ACA levels may drive CREST development, while co-occurring antibodies contribute to varied clinical presentations in ACA-positive individuals.
Area of Science:
- Rheumatology
- Immunology
- Autoimmunity
Background:
- Anticentromere antibodies (ACA) are key serological markers in autoimmune rheumatic diseases.
- Understanding the clinical heterogeneity associated with ACA is crucial for accurate diagnosis and management.
Purpose of the Study:
- To investigate the diverse clinical manifestations and serological profiles in patients positive for anticentromere antibodies (ACA).
- To explore the association between ACA levels, specific clinical features like CREST syndrome, and the presence of other autoantibodies.
Main Methods:
- Retrospective analysis of 120 patients with confirmed ACA.
- Detection of ACA via indirect immunofluorescence and anti-CENP-B antibodies by ELISA.
- Screening for additional antinuclear antibodies (ANA) using double immunodiffusion and/or ELISA.
Main Results:
- ACA were predominantly identified in patients with systemic sclerosis (SSc; 70%), particularly those with CREST features (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias).
- Overlap syndromes were common, occurring in 41.7% of SSc patients and 13.9% of non-SSc patients.
- Elevated creatine phosphokinase levels, without overt myositis, were observed in a subset of ACA-positive patients.
- Higher anti-CENP-B ELISA levels were significantly associated with SSc and the presence of CREST features, as well as Sjögren's syndrome.
Conclusions:
- ACA positivity is strongly linked to systemic sclerosis (SSc) and the CREST phenotype.
- Elevated ACA levels may be essential for the manifestation of CREST features.
- The co-occurrence of other autoantibodies (ANA) contributes to the broad spectrum of clinical heterogeneity observed in ACA-positive patients, including overlap syndromes.
Objective:
To evaluate the clinical and serological heterogeneity in patients with anticentromere antibodies (ACA).
Methods:
One hundred twenty patients with ACA were analyzed retrospectively. ACA were detected initially on the basis of indirect immunofluorescence on HEp-2 cells, and then antibodies to CENP-B were measured by ELISA. Antibodies to other nuclear antigens were also detected by double immunodiffusion and/or ELISA.
Results:
Eighty-four patients (70.0%) had systemic sclerosis (SSc; scleroderma) and 36 patients (30.0%) had other rheumatic diseases or miscellaneous disorders. Among patients with SSc, 35 patients (41.7%) had SSc in overlap mostly with Sjögren's syndrome (SS), in part with rheumatoid arthritis and/or primary biliary cirrhosis (PBC). Five of 36 patients (13.9%) without SSc also had overlap syndrome of more than 2 rheumatic diseases or PBC. All CREST features (calcinosis, Raynaud's, esophageal dysmotility, sclerodactyly, telangiectasias) were found significantly more in SSc than in other diseases. A combination of RST was the most frequently seen, followed by CREST and CRST in the SSc group. In contrast, 22 of 36 patients (61.1%) without SSc had no CREST features, and the rest had only Raynaud's phenomenon and/or telangiectasia. Twenty-five of 75 patients (33.3%) with SSc and 6 of 25 patients (24.0%) with other diseases had a slight elevation of creatine phosphokinase concentration with no apparent myositis signs and/or skin lesions, suggesting a new additional sign of patients with ACA. Seventy-two patients (60.0%) had ACA alone and 48 patients (40%) had ACA mixed with other disease marker antinuclear antibodies (ANA). ACA alone occurred more frequently in patients with SSc and in the non-overlap group, whereas patients with ACA mixed with other ANA were more frequently found in the other disease and the overlap syndrome groups. Anti-CENP-B ELISA levels of the SSc group were significantly higher than those of other disease groups in all patients, in patients with ACA alone, and in patients having ACA together with other ANA. The most frequently concurrent ANA were anti-SSA/Ro antibodies; and the other ANA, including anti-SSB/La, RNP, topoisomerase-I, Jo-1, Ku, and dsDNA antibodies, were also positive alone or combined with more than 2 ANA in patients with ACA. Five patients with CREST syndrome having ACA and anti-RNP antibodies had clinical manifestations compatible with mixed connective tissue disease. SS was found in 37.0% of patients who had higher anti-CENP-B ELISA levels and higher coincidence of anti-SSA/Ro antibodies than the patients without SS.
Conclusion:
ACA were positive mostly in patients with SSc with CREST features and partly in other rheumatic disorders. The high levels of ACA may be necessary for the development of CREST features, and frequent concurrence of other disease marker ANA may contribute to the development of heterogeneous clinical characteristics, including overlap syndrome, in patients with ACA.
