title: Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele.
abstract: OBJECTIVE
  Description of Greek patients with scleroderma with reference to (a) major organ disease, (b) autoantibodies, (c) survival rate, and (d) HLA associations.
  
  
  METHODS
  The clinical files of 254 patients were analysed retrospectively and a standardised clinical chart was completed with age at disease onset, sex, date of first and last visit, clinical and serological findings, organs affected, reasons for death, and HLA class II alleles. HLA class II alleles (DRB1, DQA1, DQB1, DPB1) were determined by polymerase chain reaction amplification using oligopeptide probes. DNA was extracted from 98 patients and 130 Greek controls.
  
  
  RESULTS
  124 patients (49%) had limited systemic sclerosis (lSSc), 114 (45%) had diffuse systemic sclerosis (dSSc), and 16 (6%) had overlap syndromes. Patients with dSSc, compared with lSSc, were characterised by a higher prevalence of lung disease (p=0.0011), oesophageal, heart, and peripheral vessel disease (p=0.027, p=0.0025, and p=0.012, respectively). Anticentromere antibodies (ACA) occurred exclusively in lSSc (34%), whereas antibodies to topoisomerase I (anti-topo I) were associated with dSSc (p<0.0001). Anti-topo I were associated with interstitial pulmonary fibrosis, oesophageal and peripheral vessel disease (p=0.028, p=0.012, and p=0.01, respectively). The HLA-DRB1*1104 allele was associated with the disease (p<0.0001) and anti-topo I (p<0.001), whereas it was not associated with ACA serum reactivity (p<0.001). Renal disease occurred in 4% of patients with SSc. The estimated survival probability for this cohort of patients with SSc, four years after the first visit, is 94.8%.
  
  
  CONCLUSIONS
  SSc among Greek subjects has the same pattern of organ disease as in other white populations. However, the prevalence of kidney disease is low. The HLA class II DRB1*1104 allele is associated with the disease, with anti-topo I, and not associated with ACA serum reactivity.
authors.affiliation: Department of Pathophysiology, Medical School, National University of Athens, Greece.
authors.forename: P G
authors.initials: PG
authors.lastname: Vlachoyiannopoulos
authors.forename: U G
authors.initials: UG
authors.lastname: Dafni
authors.forename: I
authors.initials: I
authors.lastname: Pakas
authors.forename: M
authors.initials: M
authors.lastname: Spyropoulou-Vlachou
authors.forename: C
authors.initials: C
authors.lastname: Stavropoulos-Giokas
authors.forename: H M
authors.initials: HM
authors.lastname: Moutsopoulos
mesh_terms: D000328:Adult; D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D002423:Cause of Death; D005260:Female; D005500:Follow-Up Studies; D006115:Greece / Q000453:epidemiology; D006684:HLA-DR Antigens / Q000097:blood* / Q000235:genetics; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012595:Scleroderma, Systemic / Q000235:genetics* / Q000276:immunology / Q000401:mortality*; D015996:Survival Rate
chemical_list: D001323:Autoantibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains