Analysis of systemic sclerosis in twins reveals low concordance for disease and high concordance for the presence of antinuclear antibodies

Authors

  • Carol Feghali-Bostwick,

    Corresponding author
    1. University of Pittsburgh, Pittsburgh, Pennsylvania
    Current affiliation:
    1. Pfizer Global Research and Development, Ann Arbor, Michigan
    • Division of Pulmonary, Allergy, and Critical Care Medicine and Simmons Center for Interstitial Lung Disease, University of Pittsburgh, 628 NW Montefiore, Pittsburgh, PA 15261
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  • Thomas A. Medsger Jr.,

    1. University of Pittsburgh, Pittsburgh, Pennsylvania
    Current affiliation:
    1. Pfizer Global Research and Development, Ann Arbor, Michigan
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  • Timothy M. Wright

    1. University of Pittsburgh, Pittsburgh, Pennsylvania
    Current affiliation:
    1. Pfizer Global Research and Development, Ann Arbor, Michigan
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Abstract

Objective

To examine concordance for systemic sclerosis (SSc) in monozygotic (MZ) and dizygotic (DZ) twins.

Methods

MZ and DZ twins were recruited nationwide. Zygosity was confirmed by DNA fingerprint analysis. The presence of antinuclear antibodies (ANAs) was determined using indirect immunofluorescence with HEp-2 cells as substrate. Identification of SSc-associated serum autoantibodies was performed by immunoprecipitation and double immunodiffusion. Major histocompatibility complex class II alleles were identified by polymerase chain reaction–restriction fragment length polymorphism analysis.

Results

Concordance for SSc was found to be similar in MZ and DZ twins. Overall concordance for SSc was low in the twins (4.7%). Concordance for the presence of ANAs was significantly higher in MZ twins compared with DZ twins. SSc-associated serum autoantibodies occurred exclusively in patients with SSc. The distribution of SSc-associated serum autoantibodies was similar to that observed in our large database of SSc patients. Increased HLA allele sharing was detected in DZ twins, irrespective of disease concordance.

Conclusion

These results indicate that inherited genetic factors are not sufficient to explain the development of SSc. Rather, these data indicate that inheritance may play a role in the development of serum autoantibodies in the “healthy” twin sibling of an SSc patient.

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