TY - JOUR
T1 - PM-Scl and Th/To in systemic sclerosis
T2 - a comparison of different autoantibody assays
AU - Mecoli, C. A.
AU - Gutierrez-Alamillo, L.
AU - Yang, Q.
AU - Sampedro, M.
AU - Woods, A.
AU - Hummers, L. K.
AU - Wigley, F.
AU - Shah, A. A.
AU - Casciola-Rosen, L.
N1 - Publisher Copyright:
© 2021, International League of Associations for Rheumatology (ILAR).
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
KW - Autoantibodies
KW - Methodology
KW - PM-Scl
KW - Scleroderma
KW - Th/To
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UR - http://www.scopus.com/inward/citedby.url?scp=85100178279&partnerID=8YFLogxK
U2 - 10.1007/s10067-021-05586-x
DO - 10.1007/s10067-021-05586-x
M3 - Article
C2 - 33459953
AN - SCOPUS:85100178279
SN - 0770-3198
VL - 40
SP - 2763
EP - 2769
JO - Clinical rheumatology
JF - Clinical rheumatology
IS - 7
ER -