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. 2002 Feb;61(2):121–127. doi: 10.1136/ard.61.2.121

Coexistence of antitopoisomerase I and anticentromere antibodies in patients with systemic sclerosis

T Dick 1, R Mierau 1, P Bartz-Bazzanella 1, M Alavi 1, M Stoyanova-Scholz 1, J Kindler 1, E Genth 1
PMCID: PMC1753997  PMID: 11796397

Abstract

Background: Antibodies targeting DNA topoisomerase I (ATA) or centromere proteins (ACA) are associated with clinical subsets of patients with systemic sclerosis (SSc). The occurrence of those autoantibodies is considered to be mutually exclusive.

Objective: To describe the clinical and immunogenetic data of three patients who are co-expressing both antibodies, and then review previous publications.

Methods: Both antibodies were detected by different methods, including indirect immunofluorescence technique, enzyme linked immunosorbent assay, immunodiffusion, and immunoblot. Patients were HLA typed by serological and molecular genetic methods. Data were extracted from published reports for comparison. The search for published studies was through Medline and other database research programmes.

Results: During routine laboratory diagnostics over several years three patients with scleroderma and coincidence of ATA and ACA were identified: patient 1 with diffuse SSc, Raynaud's phenomenon, puffy fingers and fingertip necrosis, contractures, and calcinosis; patient 2 with diffuse SSc, Raynaud's phenomenon, oedema of the hands, and interstitial calcinosis of hands, knees, and shoulders, and pulmonary fibrosis; patient 3 with scleroderma of hands, forearms, and face, Raynaud's phenomenon, puffy fingers, finger contractures, fingertip necrosis, and calcinosis. All three patients studied were carriers of HLA alleles known to be associated with these autoantibodies. In serial measurements the concentrations of the two antibodies showed independent or even reverse fluctuations. Screening of 100 patients with ACA for ATA and vice versa disclosed no further patients with coincidence of these antibodies. Twenty eight cases of ACA/ATA coexistence in 5423 patients (0.52%) with SSc or SSc associated symptoms were found in an analysis of published studies.

Conclusion: The expression of ATA and ACA is not totally mutually exclusive, but coincidence is rare (<1% of patients with SSc). Patients with both autoantibodies often have diffuse scleroderma and show immunogenetic features of both antibody defined subsets of SSc.

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Figure 1 .

Figure 1

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Time courses of autoantibody concentrations. Serial measurements for the three patients. Fresh sera or samples from our serum bank (after storage at -30°C) were tested by ELISA, as outlined in "Patients and methods", for ATA (triangles) and anti-CENP-B (squares).

Figure 2 .

Figure 2

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Radiograph of the right hand of patient No 2, eight years after disease onset.

Figure 3 .

Figure 3

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Clinical characteristics of patients with ACA and ATA. Clinical data of 173 patients with ACA (tested with IIFT) and 118 patients with ATA (tested with immunodiffusion) were compared by chart review. Significant differences (p<0.05, Fisher's exact test, two sided) between the two groups are marked (*).

Selected References

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