IgG and IgG4 reactivity to IL-1RA is elevated in plasma and serum of subgroups of patients with IgG4-RD. A and B, ELISA quantification of IgG reactivities to recombinant human IL-1RA in plasma from a discovery cohort consisting of healthy controls (HC; n 10), disease controls (subjects with Sjögren’s syndrome or gout; DC; n = 12), and patients with IgG4-RD (n = 13) (A) and in serum from a validation cohort consisting of age-matched healthy controls (HC; n = 50) and IgG4-RD patients (n = 122) (B). C, ELISA quantification of reactivities of individual IgG subclass (IgG1–4) antibodies to recombinant human IL-1RA in plasma from patients in the discovery cohort (HC, n = 10; IgG4-RD, n = 14). D, ELISA quantification of IgG4 reactivities to recombinant human IL-1RA in serum from a validation cohort (HC, n = 50; IgG4-RD, n = 147). Green lines indicate threshold for positive IL-1RA reactivity (3 SD above the mean optical density for DC and HC groups for the discovery and validation cohorts, respectively). Data represent means ± SD of europium counts (A, C) or optical densities (B, D) of ≥2 independent experiments. *P < 0.05, **P < 0.01, ***P<0.001 by Kruskal-Wallis (A), Mann-Whitney U-tests (B - D).