Abstract
Objective
To compare test characteristics of the Euroimmun line blot assay with other assays for two uncommon autoantibody specificities in systemic sclerosis (SSc).
Methods
Patients from the Johns Hopkins Scleroderma Center were assayed routinely using the Euroimmun platform. Patients positive for anti-Th/To (N = 73) and anti-PM-Scl (PM75 and/or PM100; N = 290) by Euroimmun were compared with SSc patients negative for these autoantibodies. For Th/To antibodies, the comparison assay was immunoprecipitation (IP), performed using 4 Th/To complex components: POP1, RPP40, RPP30, and RPP25. For anti-PM-Scl, IPs were performed with PM100 and PM75. Different Euroimmun cut-offs for assigning antibody positive status (≥ 15/+, ≥ 36/++, ≥ 71/+++) were examined. Kappa statistics were calculated to determine agreement between assays.
Results
The best performing thresholds for defining anti-PM-Scl positivity were both PM75 and PM100 ≥ 15/+ on Euroimmun, corresponding to a kappa statistic of 0.79, sensitivity 72% and specificity 100%. For anti-Th/To, kappa values were lower for all comparisons (κ < 0.5). Given the high sensitivity of defining anti-Th/To by ≥ 15/+ (91–95%), a potential approach is to use Euroimmun screening (15/+ cut-off), followed by confirmatory IP.
Conclusion
Given the increasing utilization of Euroimmun and the importance of comparing data across cohorts, continued use of this platform is warranted, acknowledging discordance with IP for some specificities. For these, using a two-step approach (Euroimmun to maximize sensitivity, confirmatory assay to increase specificity) is suggested.
Key Points: • For less common SSc autoantibody specificities, some discordances exist between IP and Euroimmun LIA. • The best performing thresholds for defining anti-PM-Scl positivity were both PM75 and PM100 ≥ 15/+ on Euroimmun. • For Th/To, a two-step approach (Euroimmun to maximize sensitivity, confirmatory assay to increase specificity) is suggested. |
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Mecoli CA, Casciola-Rosen L (2018) An update on autoantibodies in scleroderma. Curr Opin Rheumatol 30(6):548–553
Mecoli CA, Adler BL, Yang Q, Rosen A, Casciola-Rosen L, Shah AA (2020) Cancer in Systemic Sclerosis: analysis of antibodies against components of the Th/To Complex. Arthritis Rheum
Medsger TA Jr et al (2003) Assessment of disease severity and prognosis. Clin Exp Rheumatol 21(3 Suppl 29):S42–S46
Cottrell TR, Wise RA, Wigley FM, Boin F (2014) The degree of skin involvement identifies distinct lung disease outcomes and survival in systemic sclerosis. Ann Rheum Dis 73(6):1060–1066
Mecoli CA, Shah AA, Boin F, Wigley FM, Hummers LK (2018) Vascular complications in systemic sclerosis: a prospective cohort study. Clin Rheumatol 37(9):2429–2437
Simonneau G et al (2019) Haemodynamic definitions and updated clinical classification of pulmonary hypertension. Eur Respir J 53(1)
Fiorentino D, Chung L, Zwerner J, Rosen A, Casciola-Rosen L (2011) The mucocutaneous and systemic phenotype of dermatomyositis patients with antibodies to MDA5 (CADM-140): a retrospective study. J Am Acad Dermatol 65(1):25–34
Brouwer R, Pruijn GJ, van Venrooij WJ (2001) The human exosome: an autoantigenic complex of exoribonucleases in myositis and scleroderma. Arthritis Res 3(2):102–106
Hanke K, Brückner CS, Dähnrich C, Huscher D, Komorowski L, Meyer W, Janssen A, Backhaus M, Becker M, Kill A, Egerer K, Burmester GR, Hiepe F, Schlumberger W, Riemekasten G (2009) Antibodies against PM/Scl-75 and PM/Scl-100 are independent markers for different subsets of systemic sclerosis patients. Arthritis Res Ther 11(1):R22
Hamaguchi Y, Kuwana M, Takehara K (2020) Performance evaluation of a commercial line blot assay system for detection of myositis- and systemic sclerosis-related autoantibodies. Clin Rheumatol 39:3489–3497
Tansley SL et al (2020) The promise, perceptions, and pitfalls of immunoassays for autoantibody testing in myositis. Arthritis Res Ther 22(1):117
Funding
The Rheumatic Diseases Research Core Center, where the autoantibodies were assayed, is supported by NIH P30-AR070254. The autoantibody assays were funded through the Chresanthe Staurulakis Memorial Discovery Fund and NIAMS R01 AR-073208. LCR and AS are funded in part by the Donald B. and Dorothy L. Stabler Foundation. This work was also supported by NIH grant 1K23AR075898. The Johns Hopkins Scleroderma Center Research Registry receives support from the Johns Hopkins inHealth Precision Medicine Initiative and the Scleroderma Research Foundation. CM is a Jerome L Greene Scholar.
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Drs. Mecoli, Hummers, Wigley, Shah, and Casciola-Rosen contributed to the study conception and design. Material preparation, data collection, and analysis were performed by all listed authors. The first draft of the manuscript was written by C. A. Mecoli, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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All participants provided written informed consent prior to inclusion in this study. This study was approved by the Johns Hopkins IRB.
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A. A. Shah and L. Casciola-Rosen have contributed equally to this work.
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Mecoli, C.A., Gutierrez-Alamillo, L., Yang, Q. et al. PM-Scl and Th/To in systemic sclerosis: a comparison of different autoantibody assays. Clin Rheumatol 40, 2763–2769 (2021). https://doi.org/10.1007/s10067-021-05586-x
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DOI: https://doi.org/10.1007/s10067-021-05586-x