Carol Feghali-Bostwick1, Thomas A Medsger, Timothy M Wright. 1. Division of Pulmonary, Allergy, and Critical Care Medicine and Simmons Center for Interstitial Lung Disease, University of Pittsburgh, 628 NW Montefiore, Pittsburgh, PA 15261, USA.
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.
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.
Authors: Frank C Arnett; Pravitt Gourh; Sanjay Shete; Chul W Ahn; Robert E Honey; Sandeep K Agarwal; Filemon K Tan; Terry McNearney; Michael Fischbach; Marvin J Fritzler; Maureen D Mayes; John D Reveille Journal: Ann Rheum Dis Date: 2009-07-12 Impact factor: 19.103