Diagnostic Performance of Anti-Topoisomerase-I, Anti-Th/To Antibody and Anti-Fibrillarin Using Immunoblot Method in Systemic Sclerosis Related Interstitial Lung Disease Patients

Abstract

Purpose Systemic Sclerosis related Interstitial Lung Disease (SSc-ILD) is the most common clinical manifestation of SSc with a high morbidity and mortality rate. However, the Thorax High-Resolution Computed Tomography (HCRT) as the gold standard diagnostic tool for SSc-ILD is not widely equipped in health-care facilities. Recently, specific autoantibody examination (anti-topoisomerase-1 (ATA), anti-Th/To antibody, and anti-fibrillarin) has been studied and used for SSc-ILD diagnosis. This study aims to evaluate the diagnostic performance of specific autoantibody examination among SSc-ILD. Patients and Methods This retrospective study reviews data from local dedicated SSc database (Sclerosis Systemic Register System Development Electronic Medical Record) which were collected between March 2019 and August 2021. Population of this study include adult inpatients and outpatients at Dr. Hasan Sadikin General Hospital, who have been diagnosed with SSc based on ACR/EULAR 2013 criteria, which met inclusion and exclusion criteria. The SSc patients were grouped into SSc-ILD and SSc non-ILD based on HRCT and tested for SSC-ILD specific autoantibody test (ATA, anti-Th/To antibody, and anti-fibrillarin) to obtain the diagnostic performance (sensitivity, specificity, and positive- and negative-predictive value). Results A total of 74 subject grouped into 47 SSc-ILD and 27 SSc-non ILD patients. ATA validity test results showed 85.1% sensitivity, 19.2% specificity, 65.6% PPV, and 41.7% NPV. Anti-Th/To antibody obtained 27.7% sensitivity, 88.9% specificity, 81.3% PPV, and 41.4% NPV. The anti-fibrillarin validity test result showed a 12.8% sensitivity, 96.3% specificity, 85.7% PPV, and 38.8% NPV. The combination of the three parameters had 95.7% sensitivity, 18.5% specificity, 67.1% PPV, and 71.4% NPV. Conclusion The combination of the SSc-ILD specific autoantibody test and HCRT is expected to detect all affected patients. Based on these results, SSc-ILD autoantibody-specific test can be used as an alternative examination for screening and diagnosis in health-care facilities that are not equipped with HRCT.

Anti-Th/To Antibodies in Scleroderma: Good Prognosis or Serious Concern?

“…Comparing anti-Th/To patients with lcSSc to those that are ACA-positive, the first group has more subtle cutaneous and vascular involvement [ 39 ] and a mild clinical manifestation of the disease [ 40 ]. However, recent reports seem to deny the predisposition of anti-Th/To-positive patients to a mild course of the disease [ 36 , 39 , 41 ].…”

“…The profile of SSc-ILD varies widely, with less than a quarter of patients developing progressive fibrosing ILD, leading to respiratory insufficiency [ 44 , 45 ]. Due to their high specificity, anti-Th/To antibodies can serve as a reliable diagnostic marker for SSc-ILD [ 41 ]. While Mitri’s study showed that ILD is more common among Th/To patients compared to ACA-positive patients (48% vs. 13%), Moschetti et al showed that anti-Th/To-positive patients developed ILD less frequently (40% vs. 85%) and required less immunosuppression (8% vs. 41%) than anti-topo I-positive patients [ 40 ].…”

“…In a 2023 study by Logito et al [ 41 ], the anti-Th/To antibodies were reported to be 88.9% specific and 27.7% sensitive for SSc diagnosis. The positive predictive value (PPV) was 81.3%, and the negative predictive value (NPV) was 41.4%.…”

“…The positive predictive value (PPV) was 81.3%, and the negative predictive value (NPV) was 41.4%. The antibodies tended to be specific towards SSc-related ILD and were negative for non-ILD SSc patients, which makes it a valuable diagnostic clue for SSc-ILD [ 41 ]. The use of anti-Th/To and anti-fibrillarin together did not improve the specificity for SSc-ILD.…”