Background/Purpose: Disease subset has been shown to strongly correlate with survival and risk of organ complications in patients with systemic sclerosis (SSc). Nevertheless evidence in the literature suggests that SSc-specific autoantibodies may be a better predictor of SSc-associated morbidity and mortality.

Methods: We explore subset and autoantibodies as predictors of outcome in a large, well-characterised cohort of consecutive unselected SSc patients.

Results: We analysed 649 contemporary SSc patients, 59% with limited cutaneous (lc)SSc and 41% with diffuse cutaneous (dc)SSc. Of those, 25% carried anti-centromere antibody (ACA), 23% anti-topoisomerase-I antibody (ATA), 10.5% anti-RNA polymerase antibody (ARA), 4.6% anti-U3RNP,6% anti-U1-RNP, 4% anti-Pm-Scl, 18% were ANA positive, but without a defined ENA reactivity, 3.4% were ANA negative and 6% had other rarer antibodies, including Th/To, Ku, Jo1, Ro, La, SL, PL7, PL12, SL and XR.

As previously described, the strongest association with subset was observed in ACA+ patients, of whom 98% had lcSSc, while ARA+ subjects had predominantly dcSSc (91%). Although more frequent in dcSSc patients, 44% of ATA and 40% of anti-U3RNP subjects had lcSSc.

Cox regression analysis confirmed that ATA has the strongest positive association with pulmonary fibrosis (PF) – HR 3.8 (95%CI 2.9-5.1, p<0.001) and ACA has the strongest protective effect – HR 0.1 (95%CI 0.05-0.2, p<0.001). In this cohort there was also a significant negative association between PF and ARA (HR 0.5, 95%CI 0.3-0.9, p=0.018) and anti-U3RNP (HR 0.2, 95%CI 0.05-0.8, p=0.023). Although dcSSc is associated with significantly increased risk of PF, the effect of the antibodies was independent of subset.

Anti-U3RNP was associated with an increase (HR 2.9, 95%CI 1.4-5.8, p=0.003) while ATA with a reduction (HR 0.4, 95%CI 0.2-0.8, p=0.01) of the overall hazard for PH. Incidence of PH did not differ in the two subsets and correction for subset did not alter the predictive value of the antibodies.

We also confirmed the strong association between scleroderma renal crisis (SRC) and ARA (HR 7.5, 95%CI 4.2-13.2, p<0.001) and the protective role of ACA in SRC patients (HR 0.06, 95%CI 0.01-0.4, p=0.005), which were observed both within the subsets and for the cohort as a whole. There was also a negative association between SRC and ATA (HR 0.4, 95%CI 0.15-0.9, p=0.037) in the whole group, but in the subset analysis the effect held only for dcSSc patients. We found no associations between cardiac SSc and any of the antibodies.

The only antibody specificity that demonstrated significant association with survival in the whole cohort was ACA (HR 0.7, 95%CI 0.5-0.9, p=0.022), although in the analysis within subsets the association was no longer significant, suggesting that the better survival among ACA+ patients is due to the predominantly limited skin involvement in this group.

Conclusion: While ANA reactivities are strong predictors of organ complications, generally independent of disease subset, they correlate poorly with survival. Disease subset is a much better predictor of mortality and this may reflect severity rather than presence of individual organ-based complications.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/systemic-sclerosis-disease-subset-is-a-better-predictor-of-long-term-outcome-than-autoantibody-profile/