Received: 14 March 2017
Accepted: 19 January 2018
We thank all patients who have participated in this study as well as K. DeFrancesco and I. Matos for patient recruitment at the Yale Center for Clinical Investigation. We also thank J. Sterpka for technical assistance, L. Wen for providing GF NOD mice, N. Palm for use of an anaerobic chamber, M. Bosenberg for the dermatopathology samples, and S. Lewis for efforts to produce recombinant Ro60 protein. We thank W. Kwok (Benaroya Research Institute) for tetramer synthesis. Funding: This work was supported in part by grants from the NIH (K08AI095318, R01AI118855, R01 GM073863; T32AI07019), the Yale Rheumatic Diseases Research Core (NIH P30 AR053495), the Women’s Health Research at Yale, the O’Brien Center at Yale (NIH P30DK079310), the Arthritis National Research Foundation, the Arthritis Foundation, and the Lupus Research Institute. T.M.G. was supported by NIH training grant 5T32AR007016-41. K.H. was supported by NIH training grant T32GM007223 and by an NSF Predoctoral Fellowship. M.B. was supported by a Ruth L. Kirschstein National Research Service Award (F32 ES026227). The Yale Center for Clinical Investigation is supported by the Clinical and Translational Science Awards grant number UL1 RR024139 from the National Center for Research Resources, the National Center for Advancing Translational Science, and the NIH Roadmap for Medical Research. This work was also partly supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research (Xinguo Chen, K.H., M.B., S.S., and S.L.W.) and by the NIH PREP program R25GM104553 (A.J.I.). Author contributions: S.S., P.D., and S.L.W. created the list of Ro60 orthologs; T.M.G. cross-referenced them with the commensal databases and created the phylogenetic tree; and S.S. identified YrlA RNAs. T.M.G., C.D., and J.G. led human subjects protocols and recruitment, and C.D., S.C.R., and C.K. assisted in human sample processing. K.H.C. provided sera and clinical information of Harvard cohort. T.M.G. and W.E.R. performed 16S sequencing and analysis. Anaerobic bacterial cultures were done by T.M.G. and C.D. T.M.G., S.C.R., and C.K. performed qPCR. Xinguo Chen, K.H., and M.B. expressed and purified recombinant bacterial Ro60 proteins. Xinguo Chen expressed and purified the human protein from baculovirus-infected cells with assistance from T.M.G. C.D. generated the hRo60 protein produced in mammalian cells. ELISA was designed by T.M.G. and C.D. and also performed by C.K. and Xindi Chen. T cell cloning, single-cell sorting, tetramer studies, T cell proliferation, and TCR sequencing were done by C.D. Human immunoprecipitation was done by M.B. Bacterial immunoprecipitation and Northern blots were done by Xinguo Chen with assistance from T.M.G. Western blotting was performed by C.D. 16S rRNA FISH experiments were performed by C.D. Immunofluorescence was performed by C.D. and A.J.I. Mouse experiments were performed by T.M.G. with help from S.M.V., W.E.R., and C.K. IMQ mouse experiments were performed by A.J.I. and D.Z.R. M.G. provided human subjects recruitment and experimental design. A.L.G. assisted in experiment design and critical review of the manuscript. M.A.K., T.M.G., C.D., and S.L.W. wrote the manuscript. M.A.K. and S.L.W. conceived the study and provided experiment design and guidance. Competing interests: The authors declare that they have no competing interests. Data and materials availability: Human sera of lupus patients from Massachusetts are available from Yale University under a material transfer agreement with Brigham and Women’s Hospital. The 16S sequencing data have been deposited in the European Nucleotide Archive, accession PRJEB24742.