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.

Keywords:

• SSC-ILD
• ATA
• anti-Th/To antibody
• anti-fibrillarin

Suggestion

SSc-ILD specific autoantibodies of ATA, anti-Th/ToRNP and anti-fibrillarin tests have good validity that can be used as screening test and diagnosing SSc-ILD if a health facility is not equipped with HRCT as gold standard examination.

Ethics Approval and Consent to Participate

The institutional review board of the Faculty of Medicine Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung, Indonesia approved the protocol #2392020 entitled “Pengembangan Sistem Registri SSc berbasis Electronic Medical Record.” This study was approved by the Health Research Ethics Committee of Dr. Hasan Sadikin General Hospital Bandung with approval no. LB.02.01/X.6.5/239/2020. All procedures followed were in accordance with the ethical standards put forth by the Helsinki Declaration of 1975, as revised in 2000. All patients gave their informed consent to participate in the study, which was approved by the local Ethics Committee of Faculty of Medicine Universitas Padjadjaran/Dr. Hasan Sadikin General Hospital Bandung, Indonesia.

Acknowledgment

This study was supported by an internal research grant from Universitas Padjadjaran Bandung, West Java, Indonesia.

Disclosure

The authors declare no relevant financial disclosures or conflicts of interest.