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. 2020 Nov;72(11):1897-1904.
doi: 10.1002/art.41403. Epub 2020 Sep 29.

Association of Anti-Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti-Topoisomerase I-Positive Systemic Sclerosis

Maaike Boonstra  1 , Jaap A Bakker  1 , Annette Grummels  1 , Maarten K Ninaber  1 , Nina Ajmone Marsan  1 , Corrie M Wortel  1 , Tom W J Huizinga  1 , Suzana Jordan  2 , Anna-Maria Hoffman-Vold  3 , Oliver Distler  2 , René E M Toes  1 , Hans Ulrich Scherer  1 , Jeska K de Vries-Bouwstra  1
Affiliations

Association of Anti-Topoisomerase I Antibodies of the IgM Isotype With Disease Progression in Anti-Topoisomerase I-Positive Systemic Sclerosis

Maaike Boonstra et al. Arthritis Rheumatol. 2020 Nov.

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.

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Figures

Figure 1
Figure 1
Correlation between baseline levels of anti–topoisomerase I antibody (ATA) IgG, IgM, and IgA and modified Rodnan skin thickness score (MRSS) in patients from the Leiden Combined Care in Systemic Sclerosis cohort (n = 103). Spearman’s correlation analyses indicated that only anti–topoisomerase I IgG levels were significantly correlated with MRSS scores.
Figure 2
Figure 2
Percentage of patients with systemic sclerosis (among 81 with ≥1 year of follow‐up data available) who did not experience disease progression over time, according to the presence or absence of anti–topoisomerase I antibodies (ATAs) of the IgM isotype. Disease progression occurred more often in patients who were positive for anti–topoisomerase I IgM (P = 0.02, by log rank test and Mantel‐Cox test).
See this image and copyright information in PMC

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