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. 2021 May 20;12:627986. doi: 10.3389/fimmu.2021.627986

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Copyright © 2021 Grönwall, Liljefors, Bang, Hensvold, Hansson, Mathsson-Alm, Israelsson, Joshua, Svärd, Stålesen, Titcombe, Steen, Piccoli, Sherina, Clavel, Svenungsson, Gunnarsson, Saevarsdottir, Kastbom, Serre, Alfredsson, Malmström, Rönnelid, Catrina, Lundberg and Klareskog

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Cluster analysis reveals different subsets of RA patients with AMPA reactivity. (A) Hierarchical clustering of autoantibody reactivities in 384 RA patients using Ward’s method and normalized values. Four clusters of patients were further analyzed, with cluster 3 (n = 187) being primarily ACPA negative/low, and cluster 1 (n = 107), cluster 2 (n = 57) and cluster 4 (n = 33) with higher autoantibody positivity. (B) Differences in age, DAS28 disease activity, IgG anti-CCP2 and number or ACPA fine-specificities (of 10 tested) in the different clusters. P-values are indicated from Kruskal-Wallis analysis with Dunn’s correction for multiple comparisons. (C) Comparison of frequency of antibody positivity in the different patient clusters. P-values are indicated from logistic regression analysis, showing if the three ACPA+ clusters (1, 2 and 4) are significantly different when adjusting for age, HLA shared epitope, sex, smoking, and DAS28. (D) Comparison of autoantibody positivity and characteristics between cluster 2 and 4 using Fisher’s exact test.