PM-Scl and Th/To in systemic sclerosis: a comparison of different autoantibody assays

Mecoli, Christopher A.; Gutierrez‐Alamillo, Laura; Yang, Qingyuan; Sampedro, Margaret; Woods, Adrianne; Hummers, Laura K.; Wigley, Frederick M.; Shah, Ami A.; Casciola‐Rosen, Livia

doi:10.1007/s10067-021-05586-x

Cited by 5 publications

(6 citation statements)

References 10 publications

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“…Several studies have revealed that anti-Th/To antibodies are one of SSc autoantibodies with the ability to overlap polymyositis. 19 , 20 Positive anti-Th/RoRNP tests in SSc non-ILD patients could be potentially caused by overlapping case of SSc and polymyositis.…”

Section: Discussionmentioning

confidence: 99%

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

Logito¹,

Tjandrawati²,

Sugianli³

et al. 2023

OARRR

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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.

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Section: Discussionmentioning

confidence: 99%

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

Logito¹,

Tjandrawati²,

Sugianli³

et al. 2023

OARRR

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“…Anti-hydroxymethylglutaryl-coenzyme A reductase (anti-HMGCR) autoantibodies were assessed by enzyme-linked immunosorbent assay (ELISA) (Inova Diagnostics). Additional methodology regarding autoantibody assays, including immunoprecipitation for anti-NXP-2 and the handling of discordant results for multicomponent complexes (e.g., PM75 and PM100), can be found in the Supplementary Materials (20)(21)(22), available on the Arthritis & Rheumatology website at https://onlinelibrary.wiley. com/doi/10.1002/art.42311.…”

Section: Methodsmentioning

confidence: 99%

Subsets of Idiopathic Inflammatory Myositis Enriched for Contemporaneous Cancer Relative to the General Population

Mecoli

Igusa

Chen

et al. 2023

Arthritis & Rheumatology

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Objective This study investigates cancer risk in idiopathic inflammatory myopathy (IIM) relative to the general population. Methods We conducted a single‐center, retrospective cohort study of IIM patients and malignancy. Myositis‐specific and ‐associated autoantibodies were determined by Euroimmun line blot, enzyme‐linked immunosorbent assay, and immunoprecipitation. We calculated standardized prevalence ratios (SPRs) and adjusted for calendar year, age, sex, race, and ethnicity by comparing observed cancers in IIM patients versus expected cancers in the general population using the Surveillance, Epidemiology, and End Results registry. Results Of 1,172 IIM patients, 203 (17%) patients with a cancer history were studied. Over a median follow‐up of 5.2 years, the observed number of IIM patients diagnosed with cancer was increased 1.43‐fold (SPR 1.43 [95% confidence interval (95% CI) 1.15–1.77]; P = 0.002). Within 3 years of IIM symptom onset, an increased SPR was observed for anti–transcription intermediary factor 1γ (anti‐TIF1γ)–positive patients for ovarian and breast cancer (ovarian SPR 18.39 [95% CI 5.01–47.08], P < 0.001; breast SPR 3.84 [95% CI 1.99–6.71], P < 0.001). As expected, anti‐TIF1γ positivity was associated with a significantly elevated SPR; however, only 55% (36 of 66) of all cancers within 3 years of dermatomyositis onset were observed in anti‐TIF1γ–positive patients. Other myositis‐specific autoantibodies, including anti–Mi‐2, anti–small ubiquitin‐like modifier activating enzyme (SAE), and anti‐nuclear matrix protein 2 (NXP‐2), accounted for 26% (17 of 66) of cancers diagnosed within 3 years of dermatomyositis onset. No cancer association, positive or negative, was observed for patients with antisynthetase, anti–melanoma differentiation–associated protein 5 (anti–MDA‐5), or anti–hydroxymethylglutaryl‐coenzyme A reductase (anti‐HMGCR) antibodies. Conclusion In a tertiary referral center population, anti‐TIF1γ was most strongly associated with breast and ovarian cancer. Patients with antisynthetase, anti–MDA‐5, or anti‐HMGCR antibodies had the same cancer risk as the general population.

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“…Positive results were defined according to the manufacturer's instructions, with the additional requirement that patients be positive for both subunits of multicomponent complexes based on previously published data. 10 Sera were assayed for anti-U1RNP antibodies using a commercial enzyme-linked immunosorbent assay (ELISA; Inova Diagnostics). Positive results were defined as >20 units per the manufacturer's recommendations.…”

Section: Methodsmentioning

confidence: 99%

Distinct Scleroderma Autoantibody Profiles Stratify Patients for Cancer Risk at Scleroderma Onset and During the Disease Course

Kim,

Woods,

Gutierrez‐Alamillo

et al. 2023

Arthritis & Rheumatology

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ObjectivesWe examined whether an array of scleroderma autoantibodies associates with risk of cancer and could be useful tools for risk stratification.MethodsScleroderma cancer cases and scleroderma controls without cancer from Johns Hopkins and University of Pittsburgh Scleroderma Centers were studied. Sera were assayed by Lineblot and ELISA for autoantibodies against centromere, topoisomerase 1, RNA polymerase III (POLR3), PM/Scl, Th/To, NOR90, U3RNP, Ku, Ro52, U1RNP, and RNPC3. Logistic regression models were constructed to examine whether distinct autoantibodies associated with overall cancer at any time and cancer‐associated scleroderma (cancer occurring ±3 years of scleroderma onset). The effects of having >1 autoantibody on cancer were further examined using random forest analysis.Results676 cases and 687 controls were studied. After adjusting for relevant covariates, anti‐POLR3 (OR 1.47, 95%CI 1.03‐2.11) and monospecific anti‐Ro52 (OR 2.19, 95%CI 1.29‐3.74) associated with an increased overall cancer risk, whereas anti‐centromere (OR 0.69, 95%CI 0.51‐0.93) and anti‐U1RNP (OR 0.63, 95%CI 0.43‐0.93) associated with lower risk. When examining risk of cancer‐associated scleroderma, these immune responses remained associated with increased or decreased risk: anti‐POLR3 (OR 2.28, 95%CI 1.33‐3.91), monospecific anti‐Ro52 (OR 2.58, 95%CI 1.05‐6.30), anti‐centromere (OR 0.39, 95%CI 0.20‐0.74), and anti‐U1RNP (OR 0.32, 95%CI 0.11‐0.93). Anti‐Ro52 plus anti‐U1RNP or anti‐Th/To was associated with decreased cancer risk compared to anti‐Ro52 alone.ConclusionsThese data suggest that 5 distinct scleroderma immune responses, alone or in combination, may be useful tools to stratify scleroderma patients’ cancer risk. Further study examining cancer risk in autoantibody subgroups relative to the general population is warranted.image

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PM-Scl and Th/To in systemic sclerosis: a comparison of different autoantibody assays

Cited by 5 publications

References 10 publications

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

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

Subsets of Idiopathic Inflammatory Myositis Enriched for Contemporaneous Cancer Relative to the General Population

Distinct Scleroderma Autoantibody Profiles Stratify Patients for Cancer Risk at Scleroderma Onset and During the Disease Course

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