Deconstruction of the synovium of rheumatoid arthritis defines inflammatory subtypes

 

LG-P., KDD, DT, AC, GSF, MM, IS, AB-A., AMM, A. Nerviani, FR, CP, LBH and DH recruited patients and obtained synovial tissues. LWM, SMG, HP, VMH, AF, VPB, and JHA contributed to sample acquisition and processing and design of the AMP study. ED, EMG and BFB performed histological assessment of tissues. DW, KPL, AF, and VPB compiled and analyzed histological and clinical data. WA provided project management and compiled histological and clinical data. K. Wei, AHJ, GFMW, A. Nathan, and MBB designed and implemented the tissue disaggregation, cell sorting, and single-cell sequencing pipeline. AHJ, K. Wei, and GFMW oversaw and executed the tissue disaggregation pipeline. S.N., J.R.-M. and N. Meednu. performed immunofluorescence microscopy and analyzed these data together with MC and AHJKEM and IM performed and analyzed functional cellular assays. MJL, FR, and CP contributed unpublished clinical trial data. FZ, A. Nathan, N. Millard, MC, QX, MG-A., JBK, K. Weinand, JM, LR, and SR performed computational and statistical analyses. AHJ, K. Wei, MBB, JHA, LTD, DAR, FZ, A. Nathan, SR, DEO, JR-M. and AF provided input on cellular analysis and interpretation. DEO, JR-M., AF and JHA provided input for histological analyses. N. Millard and KS implemented the website. SR, MBB, JHA, LTD, and DAR supervised the study. FZ, AHJ, A. Nathan, N. Millard, QX, and SR wrote the first draft. FZ, AHJ, A. Nathan, K. Wei, N. Millard, DAR, LTD, JHA, MBB, and SR edited the draft. Members of the AMP RA/SLE Network contributed to this work by managing patient recruitment, managing clinical data, obtaining and processing synovial tissue samples, managing biorepositories, performing histological or computational analyses, providing software code, providing website support and/or providing input for data analysis. and interpretation. All authors participated in editing the final manuscript.

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