Refining serological scores in rheumatoid arthritis classification: an international study.
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Van Hoovels Lieve, Chatzichristos Christos, Irure-Ventura Juan, Vandebeek Daphné, Lodewijckx Elke, Vander Cruyssen Bert, Sieghart Daniela, Bonroy Carolien, Nagy Eszter, Pullerits Rille, Čučnik Saša, Dahle Charlotte, Heijnen Ingmar, Bernasconi Luca, Benkhadra Farid, Bogaert Laura, Van Den Bremt Stefanie, Van Liedekerke Ann, Vanheule Geert, Robbrecht Johan, Wirth Claudine, Mueller Rüdiger B, Kyburz Diego, Sjöwall Christopher, Kastbom Alf, Ješe Rok, Jovancevic Boja, Kiss Emese, Jacques Peggy, De Vos Maarten, López-Hoyos Marcos, Steiner Günter, Verschueren Patrick, Bossuyt Xavier
Аннотация
MATERIALS AND METHODS: Diagnostic samples from 398 patients with RA and 448 diseased controls (DC) were evaluated with RF and ACPA assays from five different manufacturers. A grid search was conducted across all possible integer score pairs for RF and ACPA to identify the weighting combination that optimised the specificity of RA classification. This combination was applied in a refined scoring system (RSS) for three confirmatory cohorts comprising, respectively, 67, 157 and 132 patients with RA and 441, 153 and 193 DC.
FINDINGS: In the investigative cohort, the optimal combination of weighting scores was characterised by higher scores for ACPA, higher antibody levels and double RF/ACPA positivity.Applying the optimal combination of weighting scores decreased misclassification compared with the 2010 RA classification criteria, minimally affecting sensitivity. For seropositive patients, RSS significantly lowered misclassification from 38.3-55.8% to 15.0-26.9%.The improved specificity of RSS (compared with the 2010 criteria) was validated in the confirmatory cohorts. Considering only seropositive patients, the RSS significantly decreased RA misclassification (8.6-36.8% vs 20.0-78.9%), minimally affecting the sensitivity (86.7-97.3% vs 86.7-96.0%).
INTERPRETATION: Serological weight factors for RA classification can be improved by taking into account the antibody type, the antibody levels and single or combined positivity. The application of an RSS reduced the number of RA misclassifications.