CYTOGENETIC SURVEY IN SYSTEMIC-SCLEROSIS - CORRELATION OF ANEUPLOIDY WITH THE PRESENCE OF ANTICENTROMERE ANTIBODIES

Previous cytogenetic studies of patients with systemic sclerosis have obtained conflicting results regarding the presence of chromosomal ano malies. We studied 38 patients and 15 controls to determine whether th ese inconsistencies were due to differences in the subgroups of patien ts who were studied. Because many patients with systemic sclerosis pro duce autoantibodies to protein antigens that have been implicated in c hromosome structure and function, we further hypothesized that the pre sence of these autoantibodies might correlate with the presence of chr omosomal anomalies. Patients were classified into clinical subgroups b ased on the extent of their disease. Their sera were assayed for autoa ntibodies to topoisomerase I and centromere proteins (CENP-A, CENP-B, and CENP-C) by immunoblotting. Cytogenetic analyses for aneuploidy and chromosome breaks were performed. Anticentromere antibody positive (A CA+) patients had significantly more aneuploidy than either ACA negati ve (ACA-) patients or controls (P = 0.041). Although the patient group , when considered as a whole, had significantly greater aneuploidy tha n the control group (P < 0.005), patients who were ACA- did not have m ore aneuploidy than the controls had. Patients with Type I disease (sc lerodactyly), the majority of whom were ACA+, also had significantly m ore aneuploidy than did either the controls or patients with Type III (diffuse) disease, most of whom were ACA- (P < 0.005). ACA+ patients a lso had more chromatid breaks than the controls had (P < 0.05). The co rrelation between the presence of ACAs and chromosomal aneuploidy sugg ests that aneuploidy may be the result of nondisjunction secondary to centromeric dysfunction. In support of this hypothesis, the ACA+ patie nts who had antibodies to CENP-C exhibited more chromosomal aneuploidy than did either anti-CENP-A or anti-CENP-B positive patients (P < 0.0 48). Unlike CENP-A and CENP-B, which are present at both functional an d inactivated centromeres, CENP-C is present at the kinetochore of fun ctional centromeres.