Abstract
OBJECTIVE: Anti-topoisomerase I (anti-topo I) autoantibodies in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relationship between anti-topo I antibody response and disease course has not yet been fully evaluated. This study was undertaken to gain insight into the association between characteristics of the anti-topo I antibody response and clinical disease course in SSc patients positive for anti-topo I antibodies. METHODS: Levels of anti-topo I IgG, anti-topo I IgM, and anti-topo I IgA were assessed in consecutive serum samples obtained from patients at baseline who were positive for anti-topo I IgG in the Leiden Combined Care In Systemic Sclerosis (CCISS) cohort. One-year disease progression was defined by a relevant increase in modified Rodnan skin thickness score (MRSS), decline in pulmonary function, development of digital ulcers, renal crisis, and pulmonary hypertension, and/or mortality. Validation was performed in SSc patients who were positive for anti-topo I from the Oslo University Hospital and University Hospital Zurich. RESULTS: Of the 103 patients with anti-topo I IgG in the CCISS cohort, clinical data were available to assess 1-year disease progression in 81 patients. Of these 81 patients, 23 (28%) had disease progression. At baseline, patients with disease progression were significantly more often anti-topo I IgM-positive than those who did not experience disease progression (21 [91%] of 23 versus 33 [57%] of 58; P < 0.01). This finding was confirmed in the independent validation samples. CONCLUSION: In SSc patients who were anti-topo I IgG-positive, presence of anti-topo I IgM, which might be considered as a surrogate for an ongoing autoreactive B cell immune response, is associated with disease progression.