Presence of IgM anti‐topoisomerase I antibodies is associated with disease progression in anti‐topoisomerase I IgG positive systemic sclerosis
2020
BACKGROUND Anti-topoisomerase I auto-antibodies (ATA) in systemic sclerosis (SSc) are associated with diffuse skin involvement and interstitial lung fibrosis. Thus far, however, the relations between the ATA response and disease course have not yet been fully evaluated. OBJECTIVES To gain insight into the relation between characteristics of the ATA immune response and clinical disease course in ATA+ SSc. METHODS ATA-IgG, -IgM and -IgA levels were assessed in consecutive serum samples of baseline ATA-IgG+ patients from the Leiden Combined Care In Systemic Sclerosis cohort (CCISS). One-year disease progression was defined by a relevant increase in modified Rodnan Skin Score (mRSS), decline in pulmonary function tests, development of digital ulcers, renal crisis, pulmonary hypertension and/or mortality. Validation was performed in ATA+ SSc patients from the Oslo University Hospital and University Hospital Zurich RESULTS: Of 103 ATA-IgG+ patients available in the CCISS cohort, 81 patients had clinical data available to assess one-year disease progression. Of these 81 patients, 23 patients (28%) showed disease progression. At baseline, disease-progressors were significantly more often ATA-IgM+ compared to non-progressors (21/23 [91%] vs 33/58 [57%], p<0.01). This finding was confirmed in the independent validation samples. CONCLUSION In ATA-IgG+ SSc patients, presence of ATA-IgM, which might be taken as a surrogate for an ongoing auto-reactive B cell immune response, is associated with disease progression.
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