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Systemic scleroderma in Greece: low mortality and strong linkage with HLA-DRB1*1104 allele
P G Vlachoyiannopoulos1, U G Dafni, I Pakas
1Department of Pathophysiology, Medical School, National University of Athens, Greece.
Insights
This study describes Greek patients with scleroderma (SSc), finding similar organ involvement to other populations but lower kidney disease rates. The HLA-DRB1*1104 allele is linked to SSc and specific autoantibodies.
Area of Science:
- Rheumatology and Immunology
- Genetics and Epidemiology
Background:
- Systemic sclerosis (SSc) is a complex autoimmune disease with variable clinical manifestations.
- Understanding population-specific characteristics is crucial for disease management and research.
Purpose of the Study:
- To characterize Greek patients with SSc based on organ involvement, autoantibodies, survival, and HLA associations.
- To compare findings with other white populations.
Main Methods:
- Retrospective analysis of clinical files from 254 SSc patients.
- Standardized chart completion including demographics, clinical, serological, and organ involvement data.
- HLA class II typing (DRB1, DQA1, DQB1, DPB1) using polymerase chain reaction in patients and controls.
Main Results:
- Limited SSc (lSSc) in 49%, diffuse SSc (dSSc) in 45%.
- dSSc associated with higher prevalence of lung, esophageal, heart, and peripheral vessel disease.
- Anticentromere antibodies (ACA) exclusive to lSSc; anti-topoisomerase I (anti-topo I) associated with dSSc and interstitial lung disease.
- HLA-DRB1*1104 allele associated with SSc and anti-topo I, but not ACA.
- Renal disease in 4%; 4-year survival probability is 94.8%.
Conclusions:
- Greek SSc patients exhibit similar organ disease patterns to other white populations.
- A notably low prevalence of kidney disease was observed in this cohort.
- The HLA-DRB1*1104 allele is a significant genetic marker associated with SSc and anti-topo I antibodies in this population.
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%.
Conclusion:
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.