Authors: Maaike Boonstra, Jaap A. Bakker, Annette Grummels, Maarten K. Ninaber, Nina Ajmone Marsan, Corrie M. Wortel, Tom W. J. Huizinga, Suzana Jordan, Anna‐Maria Hoffman‐Vold, Oliver Distler, René E. M. Toes, Hans Ulrich Scherer, Jeska K. de Vries‐Bouwstra
Published: 2020-06-17
DOI: 10.1002/art.41403
Source: Full article
ObjectiveAnti–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.MethodsLevels 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.ResultsOf 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.ConclusionIn 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.