South Australian Scleroderma Register: autoantibodies as predictive biomarkers of phenotype and outcome.
OBJECTIVE
To investigate the relationship between scleroderma-specific autoantibodies and clinical phenotype and survival in South Australian patients with scleroderma.


METHODS
Two cohorts of patients were studied from the South Australian Scleroderma Register (SASR). In the first, the sera of 129 consecutive patients were analyzed for anticentromere (ACA), anti-Scl70, anti-RNA polymerase III, anti-U1RNP, anti-Th/To, anti-Pm/Scl, anti-Ku and anti-fibrillarin antibodies using the Euroline immunoblot assay. Statistical analysis was performed to look for a significant association between specific antibodies and various clinical features. In the second cohort survival from first symptom onset was analyzed in 285 patients in whom the autoantibody profile was available, including ACA, Anti-Scl70, anti-U1RNP and anti-RNA polymerase III measured using multiple methods. Survival analysis compared mortality between different groups of patients with specific antibodies.


RESULTS
ACA, Th/To and Ku antibodies were associated with limited scleroderma, Scl70 and RNA Pol III antibodies were associated with diffuse scleroderma and antibodies to U1RNP were associated with overlap syndrome. Significant associations between Scl70 and interstitial lung disease (P = 0.004), RNA Pol III and renal crisis (P = 0.002), U1RNP and pulmonary hypertension (P = 0.006) and Th/To and pulmonary hypertension (P = 0.034) were seen. Trends were observed with an increased frequency of lung disease with Pm/Scl and Th/To and an increased frequency of myositis with Ku. The presence of Scl70, RNA Pol III and U1RNP was associated with significantly reduced survival as compared with patients with ACA.


CONCLUSIONS
Scleroderma-specific autoantibodies are associated with clinical phenotype and survival.
Rheumatology Unit, Repatriation General Hospital, Daw Park, South Australia, Australia. graffa@hotmail.com
Scott W
SW
Graf
Paul
P
Hakendorf
Sue
S
Lester
Karen
K
Patterson
Jenny G
JG
Walker
Malcolm D
MD
Smith
Michael J
MJ
Ahern
Peter J
PJ
Roberts-Thomson
D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D012042:Registries; D045743:Scleroderma, Diffuse / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D045745:Scleroderma, Limited / Q000150:complications / Q000175:diagnosis* / Q000276:immunology / Q000401:mortality; D013021:South Australia / Q000453:epidemiology; D013997:Time Factors
D000974:Antibodies, Antinuclear; D001323:Autoantibodies; D015415:Biomarkers