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. 2022 May 19;28(6):1256–1268. doi: 10.1038/s41591-022-01789-0

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Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — a, Classification into synovial pathotypes according to semiquantitative scores for CD3⁺ T cells, CD20⁺ B cells, CD68⁺ macrophages and CD138⁺ plasma cells, with representative examples from patients classified as lymphomyeloid (CD20 ≥ 2 and/or CD138≥2), diffuse-myeloid (CD68SL≥2, and CD20/CD138<2) or fibroid/pauci-immune (CD68SL/CD20/CD138<2). Right, 16-week CDAI 50% response in patients stratified by pathotype (n = 152). Bar plots showing the proportion of CDAI 50% responders for rituximab (in blue) and tocilizumab (in yellow) within each pathotype, with corresponding exact numbers. Fisher's test, exact P values for P < 0.05. b, Approach to in silico deconvolution of synovial tissue using MCP-counter. c, MCP-counter scores for each cell type compared among CDAI 50% responders (R) and nonresponders (NR). Bar plots indicate nominal log₁₀ P values for tocilizumab and –log₁₀ P values for rituximab (two-sided Mann–Whitney test); dashed lines correspond to P = 0.05. Boxplots (right) show median and first and third quartiles, whiskers extending to the highest and lowest values. d–f, 16-week CDAI 50% response in patients stratified into B and T cell poor/rich (d) and macrophage/mDC poor/rich (e) according to median MCP-counter scores for individual cells (rich if above median, poor if below), or by combining B cell and macrophage/mDC scores from d,e (f). Exact P values shown when <0.05, two-sided Fisher's test comparing the proportions of responders to rituximab (in blue) and tocilizumab (in yellow). g–i, Longitudinal disease activity scores (CDAI), shown as mean ± s.d., for each month from baseline to 16 weeks for patients randomized to rituximab (in blue) or tocilizumab (in yellow) and classified as B and T cell poor/rich (g), macrophage/mDC poor/rich (h) and combined B cell/macrophage poor/rich (i). Comparison of CDAI between the two medications at individual time points by two-sided Mann–Whitney test, exact P values for <0.05 (adjustment for multiple comparisons by FDR). P values for the drug × time interaction term (two-way repeated-measures analysis of covariance) are shown when <0.05. c–i, n = 133 patients with baseline RNA-seq. NK, natural killer cells. mDC, myeloid dendritic cells.