Background/Purpose: Systemic sclerosis (SSc) is a progressive autoimmune disease with high morbidity and mortality, making early diagnosis and management critical. Anti-Topoisomerase I antibody (anti-Topo I, also known as Scl-70) has important diagnostic and prognostic roles in SSc. Although positivity for anti-Topo I antibody is considered highly specific for SSc, the testing methods typically utilized in commercial laboratories have lower specificity than the immunodiffusion method. To highlight potential harms of a false-positive anti-Topo I antibody result, we describe a series of cases in which patients who tested positive for anti-Topo I antibody in a commercial laboratory were found to be negative for anti-Topo I antibody by the immunodiffusion method.

Methods: Patients seen in our clinic who had previously tested positive for anti-Topo I antibody performed by a commercial laboratory, but who lacked sufficient clinical criteria to be classified as SSc, were invited to undergo testing for anti-Topo I antibody by immunodiffusion in our research laboratory. Each patient’s clinical features, commercial anti-Topo I antibody results, additional diagnostic testing, and clinical diagnosis at initial and follow up visits were recorded.

Results: Over a six-year period, 19 patients who fulfilled the above criteria underwent testing for anti-Topo I antibody by immunodiffusion (Table 1). 16 (84.2%) were found to be negative. 11 of the 19 patients (57.9%) had at least one follow up visit, typically 6-12 months after initial visit. Of those 11 patients with at least one follow up visit, all three patients who tested positive for anti-Topo I antibody by immunodiffusion, but none of the eight patients who tested negative, developed sufficient criteria to be classified as SSc on follow up. One of the patients with a false-positive anti-Topo I antibody result was diagnosed with morphea, one with Sjogren’s syndrome, one with antiphospholipid antibody syndrome, and two with undifferentiated connective tissue disease. The other 11 patients with false-positive anti-Topo I antibody results (68.8%) did not have a rheumatologic condition in the judgement of the treating physician. 7 of the 16 patients with false-positive anti-Topo I antibody (43.8%) had undergone chest CTs to screen for interstitial lung disease, one had been started on treatment with Mycophenolate Mofetil, and one had undergone pre-evaluation for autologous hematopoietic stem cell transplantation.

Conclusion: Our findings highlight the propensity of commercial laboratories to produce false-positive anti-Topo I antibody results. In the cases reported here, unnecessary referrals to a scleroderma specialty clinic, and in some cases unnecessary chest CTs, occurred after patients tested falsely positive for anti-Topo I antibody, demonstrating some of the potential negative impacts on patients and the healthcare system. While a thorough history and physical exam remain the mainstays of SSc evaluation, testing for anti-Topo I antibody using a more specific method such as immunodiffusion would likely help physicians and patients to avoid misdiagnoses, unnecessary referrals and diagnostic testing, and potentially risky treatments.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/false-positive-anti-topoisomerase-i-scl-70-antibody-results-a-case-series-from-a-scleroderma-referral-center/