Background Systemic Sclerosis (SSc) shows a heterogeneous clinical presentation, characterized by marked skin and internal organ fibrosis and vascular dysfunction, associated with immunological abnormalities. A varied panel of SSc-related auto-antibodies has been described, and there is a growing interest to establish their prevalence and clinical associations in populations of different ethnicities.
Objectives To evaluate the frequency and the putative associations of a panel of SSc-related auto-antibodies with demographic and clinical features in a large SSc cohort.
Methods We analyzed serum of 328 consecutive SSc adult patients attended at the Scleroderma Outpatient Clinic of a tertiary referral university hospital in Brazil, classified according to the ACR/EULAR 2013 SSc criteria: 32% had diffuse cutaneous SSc and 68% limited cutaneous SSc. Clinical and demographic data were obtained through a review of the electronic register database. Serum samples were analyzed for the presence of autoantibodies using commercially available standardized kits.
Results ANA positivity was 88%, in the following patterns: centromeric (26%), nuclear homogeneous/nucleolar (18%), nucleolar (16%), nuclear homogeneous (12%), nuclear speckled (12%), dense fine speckled (2%), nucleolar speckled (<1%), and cytoplasmatic (1%). Anti-Scl70 was present in 92 (28%), anticentromere (ACA) in 83 (25%), anti-fibrillarin in 39 (12%), anti-RNA Pol III in 23 (7%), anti-Th/To in 17 (5%), anti-PM-Scl in 16 (5%), anti-Ku in 12 (4%), and anti-NOR in 6 (2%), and anti-Ro/SSA was positive in 96 patients (29%). Anti-Scl70 was associated with the nuclear homogeneous/nucleolar and nuclear homogeneous patterns, while symptomatic ILD was associated to both ANA patterns (p<0.001 and 0.005), digital ulcers were associated with the nuclear homogeneous/nucleolar patterns (p=0,042). ACA was associated with female gender (p<0.001), white ethnicity (trend; p=0.076), limited cutaneous SSc (p<0.001), calcinosis (p=0.002), asymptomatic ILD (p<0.001), and isolated PAH (p<0.001). Otherwise, anti-Scl70 was associated with male gender (p=0.034), diffuse cutaneous SSc (p<0.001), digital ulcers (p<0.001), symptomatic ILD (p<0.001), and use of immunosuppressive drugs (cyclophosphamide, azathioprine, mycophenolate mofetil (p<0.001). Three patients were diagnosed as scleroderma renal crisis and two of then presented anti-RNA pol III, that was associated with diffuse cutaneous SSc (p=0.011). Anti-fibrillarin was associated with symptomatic ILD (trend; p=0.072) and heart involvement (p=0,043). Anti-Ku was associated with finger amputation (p=0.019). Anti-PM-Scl, anti-Th/To and anti-NOR90 did not show any specific association.
Conclusions Among the different SSc-related auto-antibodies, anti-Scl70 and ACA clearly characterize distinct demographic and clinical presentations. Our study also identified new clinical associations, among anti-fibrillarin and heart involvement and anti-Ku with digital amputation, as well as the concomitance of anti-Ro/SSA with anti-Scl70 being associated with poor prognosis.
Disclosure of Interest None declared