Anticentromere-A and Anticentromere-B Antibodies Show High Concordance and Similar Clinical Associations in Patients with Systemic Sclerosis

Hanke, Katharina; Becker, Mike; Brueckner, Claudia S; Meyer, Wolfgang; Janssen, A.; Schlumberger, Wolfgang; Hiepe, Falk; Burmester, G.-R.; Riemekasten, Gabriela

doi:10.3899/jrheum.100402

Cited by 22 publications

(23 citation statements)

References 15 publications

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“…In accordance with previous reports [8,9,12,15,33,36,38,39], these patients were less often male, were older at disease onset and had a more limited extension of cutaneous involvement, as documented by a much lower OR for a Rodnan skin score (RSS) above 10 (Table 5) and by a very significantly lower mean RSS (Table 6). They had less involvement of internal organs (pulmonary fibrosis, cardiac, musculoskeletal and oral involvement), with the exception of pulmonary hypertension.…”

Section: Resultssupporting

confidence: 91%

“…They had less involvement of internal organs (pulmonary fibrosis, cardiac, musculoskeletal and oral involvement), with the exception of pulmonary hypertension. An association of ACA with pulmonary hypertension has been observed in several previous reports [2,12,33,40], but not all of them [13,36,38,39]. Digital ulcers in our patients with ACA were less common compared to American patients [2] and more similar to European [9,12,38] and Japanese patients [34].…”

Section: Resultssupporting

confidence: 63%

“…An association of ACA with pulmonary hypertension has been observed in several previous reports [2,12,33,40], but not all of them [13,36,38,39]. Digital ulcers in our patients with ACA were less common compared to American patients [2] and more similar to European [9,12,38] and Japanese patients [34]. Nevertheless, the presence of ACA does not by any means preclude digital ulcers.…”

Section: Resultsmentioning

confidence: 92%

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Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

et al. 2011

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IntroductionIn the present study, we analysed in detail nuclear autoantibodies and their associations in systemic sclerosis (SSc) patients included in the German Network for Systemic Scleroderma Registry.MethodsSera of 863 patients were analysed according to a standardised protocol including immunofluorescence, immunoprecipitation, line immunoassay and immunodiffusion.ResultsAntinuclear antibodies (ANA) were detected in 94.2% of patients. In 81.6%, at least one of the autoantibodies highly associated with SSc or with overlap syndromes with scleroderma features was detected, that is, anti-centromere (35.9%) or anti-topoisomerase I (30.1%), followed in markedly lower frequency by antibodies to PM-Scl (4.9%), U1-ribonucleoprotein (U1-RNP) (4.8%), RNA polymerases (RNAPs) (3.8%), fibrillarin (1.4%), Ku (1.2%), aminoacyl-transfer RNA synthetases (0.5%), To (0.2%) and U11-RNP (0.1%). We found that the simultaneous presence of SSc-associated autoantibodies was rare (1.6%). Furthermore, additional autoantibodies were detected in 55.4% of the patients with SSc, of which anti-Ro/anti-La, anti-mitochondrial and anti-p25/p23 antibodies were most frequent. The coexistence of SSc-associated and other autoantibodies was common (43% of patients). SSc-associated autoantibodies disclosed characteristic associations with clinical features of patients, some of which were previously not acknowledged.ConclusionsThis study shows that five autoantigens (that is, centromere, topoisomerase I, PM-Scl, U1-RNP and RNAP) detected more than 95% of the known SSc-associated antibody responses in ANA-positive SSc patients and characterise around 79% of all SSc patients in a central European cohort. These data confirm and extend previous data underlining the central role of the determination of ANAs in defining the diagnosis, subset allocation and prognosis of SSc patients.

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Section: Resultssupporting

confidence: 91%

Section: Resultssupporting

confidence: 63%

Section: Resultsmentioning

confidence: 92%

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Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

et al. 2011

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“…[4] Previous investigations in anti-CENP-positive patients using the more sensitive CENP ELISA did not find differences in disease features between those with antibodies to CENP-A versus CENP-B. [12,20] Here, we looked at a still finer level of antibody specificity, by limiting our analysis to the first epitope, Ap1–17, and focusing on shorter peptide sequences within it. From our previous study, [21] we had phage clones expressing 12-mer peptides that were specifically recognized by sera from a small number of SSc patients.…”

Section: Discussionmentioning

confidence: 99%

“…[19] Although these chromatin-binding proteins are unrelated, patients often have antibodies to both. [3] As differences in disease features were not found between CENP-A-positive and CENP-B-positive patients, [12,20] it is important to examine the fine specificities within these antibody populations.…”

Section: Introductionmentioning

confidence: 99%

Subspecificities of anticentromeric protein A antibodies identify systemic sclerosis patients at higher risk of pulmonary vascular disease

et al. 2016

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Patients with systemic sclerosis (SSc) who express autoantibodies to centromeric proteins (CENPs) are at risk of developing pulmonary vascular disease and pulmonary arterial hypertension without fibrosis. Currently no biomarkers are available to predict these complications. We previously characterized the fine specificity of anti-CENP-A antibodies in SSc by screening a phage display library (expressing random 12-mer peptides), and identified phage clones whose peptides were differentially recognized by patients’ autoantibodies. Here, we examined if subgroups of SSc patients with different anti-CENP-A antibody subspecificities also differ clinically, and if serum reactivity to phage-displayed peptides can predict pulmonary vascular disease.Clinical data and serum samples were collected from 84 anti-CENP-A-positive SSc patients. Indirect ELISAs were used to test serum reactivity. Pulmonary vascular disease was defined as high systolic pulmonary arterial pressure (sPAP) and low diffusing lung capacity for carbon monoxide (DLCO; percent of predicted values).Sera were screened for reactivity to peptides expressed by phage clones pc4.2 and pc14.1, confirming our earlier observation of differential specificities. Linear regression showed that the levels of antibodies specific for the 2 phage clones were associated with clinical features of pulmonary vascular disease, but in opposite ways: anti-pc4.2 antibodies were positively associated with sPAP and inversely associated with DLCO, whereas anti-pc14.1 antibodies were inversely associated with sPAP and positively associated with DLCO. Anti-pc4.2 and anti-pc14.1 antibody levels predicted sPAP independently of DLCO. These associations were confirmed by logistic regression using antibodies as predictors and dichotomized sPAP (cutoff, 45 mm Hg) as outcome. The ratio of the 2 antibody levels was a useful marker in predicting high sPAP.This study demonstrates that some SSc clinical features associate with subspecificities of anti-CENP-A antibodies. Moreover, it shows that a simple, inexpensive phage-based assay can predict which SSc patients have high sPAP and low DLCO, hence who are at greater risk of developing pulmonary arterial hypertension. The ability to identify these at-risk patients can contribute to clinical efficiency and effectiveness. Further research into the peptides expressed by the phage clones may reveal the molecular mechanisms that put some anti-CENP-A-positive patients at greater risk than others for pulmonary vascular disease.

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Diagnostic accuracy and predictive value of autoantibody profiles in patients with systemic sclerosis: a single-center study

Zhang

Zhao

et al. 2023

Clin Rheumatol

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Anticentromere-A and Anticentromere-B Antibodies Show High Concordance and Similar Clinical Associations in Patients with Systemic Sclerosis

Cited by 22 publications

References 15 publications

Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

Frequency of disease-associated and other nuclear autoantibodies in patients of the German network for systemic scleroderma: correlation with characteristic clinical features

Subspecificities of anticentromeric protein A antibodies identify systemic sclerosis patients at higher risk of pulmonary vascular disease

Diagnostic accuracy and predictive value of autoantibody profiles in patients with systemic sclerosis: a single-center study

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