M. Choi, Irene K. Chen, A. Clarke, M. Fritzler, K. Buhler, M. Urowitz, J. Hanly, C. Gordon, Y. Pierre, S. Bae, J. Diaz, J. Sánchez-Guerrero, S. Bernatsky, D. Wallace, D. Isenberg, Anisur Rahman, J. Merrill, P. Fortin, D. Gladman, I. Bruce, M. Petri, E. Ginzler, M. Dooley, R. Ramsey‐Goldman, S. Manzi, A. Jonsen, G. Alarcón, R. Vollenhoven, C. Aranow, M. Mackay, G. Ruiz‐Irastorza, Sam Lim, M. Inanç, K. Kalunian, S. Jacobsen, C. Peschken, D. Kamen, A. Askanase, D. Sontag, J. Buyon, K. Costenbader
{"title":"1704 Identifying clusters of longitudinal autoantibody profiles associated with systemic lupus erythematosus disease outcomes","authors":"M. Choi, Irene K. Chen, A. Clarke, M. Fritzler, K. Buhler, M. Urowitz, J. Hanly, C. Gordon, Y. Pierre, S. Bae, J. Diaz, J. Sánchez-Guerrero, S. Bernatsky, D. Wallace, D. Isenberg, Anisur Rahman, J. Merrill, P. Fortin, D. Gladman, I. Bruce, M. Petri, E. Ginzler, M. Dooley, R. Ramsey‐Goldman, S. Manzi, A. Jonsen, G. Alarcón, R. Vollenhoven, C. Aranow, M. Mackay, G. Ruiz‐Irastorza, Sam Lim, M. Inanç, K. Kalunian, S. Jacobsen, C. Peschken, D. Kamen, A. Askanase, D. Sontag, J. Buyon, K. Costenbader","doi":"10.1136/lupus-2021-lupus21century.99","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.99","url":null,"abstract":"","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"33 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"120963766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Michael H Lee, S. Tursi, Lauren K Nicastro, Benjamin L Green, R. Caricchio, Ç. Tükel, S. Gallucci
{"title":"1701 Curli amyloid/DNA complexes from bacterial biofilms break tolerance in murine lupus using T cell-independent and T cell-dependent modalities","authors":"Michael H Lee, S. Tursi, Lauren K Nicastro, Benjamin L Green, R. Caricchio, Ç. Tükel, S. Gallucci","doi":"10.1136/lupus-2021-lupus21century.96","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.96","url":null,"abstract":"Background Epidemiological studies suggest that bacterial infections promote SLE disease in predisposed individuals, but the underlying mechanisms remain unknown. We have found that a subset of SLE patients has asymptomatic bac-teriuria associated with markers of inflammation and flares, suggesting that chronic exposures to microbial products may trigger flares in lupus. Our labs have shown that the bacterial amyloid curli, expressed in multicellular commun-ities ( biofilms) by many bacteria including E. coli , plays a major role in triggering lupus autoimmunity during infec-tion. Curli amyloid/DNA complexes strongly activate dendritic cells and macrophages. When given systemically, curli/DNA complexes and infections with curli-expressing E. coli trigger production of anti-dsDNA and anti-chroma-tin autoantibodies in lupus prone mice and in wild type mice. This stimulation is diminished in TLR2 or TLR9 deficient mice, suggesting a TLR-mediated activation of innate immunity. We have now focused on the effects of curli/DNA complexes on B cells. DNA complexes biofilms or infected with amyloid for short and long-term studies.","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"123131297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
D. Rawlings, Fahd A. Al Qureshah, Sara Sagadiev, Christopher D. Thouvenel, Shuozhi Liu, Zhaolin Hua, B. Hou, Mridu Acharya, Richard G. James
{"title":"1703 Activated PI3Kδ signals compromise plasma cell survival via limiting autophagy and increasing endoplasmic reticulum stress","authors":"D. Rawlings, Fahd A. Al Qureshah, Sara Sagadiev, Christopher D. Thouvenel, Shuozhi Liu, Zhaolin Hua, B. Hou, Mridu Acharya, Richard G. James","doi":"10.1136/lupus-2021-lupus21century.98","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.98","url":null,"abstract":"","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"22 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122309879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"1705 Protein assemblages are newly described intracellular structures that may play a role in shaping the lupus autoantibody repertoire","authors":"P. L. Carl, H. Fried, P. Cohen","doi":"10.1136/lupus-2021-lupus21century.100","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.100","url":null,"abstract":"1706 Figure 1 Abstracts A72 Lupus Science & Medicine 2021;8(Suppl 2):A1–A75 coright. on Jauary 6, 2022 by gest. P rocted by httpupus.bm jcom / Lpus S ci M d: frst pulished as 10.1136/lupu-lupus21century.101 on 4 N ovem er 221. D ow nladed fom Conclusions These data (Cui, et al. PLoS One 2018;13: e01931711), also show strong association of EBV with SLE with anti-EBNA1 being more frequent in SLE cases than in concurrent patient controls, supporting the known association of EBV infection with SLE. Further, anti-EBNA1 is virtually always present in SLE and is present more frequently in EBA-infected SLE patients than in EBV-infected controls, consistent with the hypothesis that anti-EBNA1 is the usual immune response foundation from which pathogenic SLE autoimmunity emerges. These results support a model of the etiology of SLE that begins with EBV infection, leading to anti-EBNA1 antibodies. Then, a subset of these heteroimmune anti-EBNA1 antibodies cross react with SLE autoantigens (e.g., Sm as in figure 1, (EBV image, courtesy of NIAID/NIH; SLE malar rash image, courtesy of Mayo Foundation, all rights reserved)) that then mature into an SLE autoantibody response and result in in life-threatening clinical SLE. The specific role of the other EBV gene products, EBNA2, EBNA3C, and EBNALP, in this process (figure 1) await elucidation. Acknowledgments Support is appreciated from US Department of Veterans Affairs Merit Award (I01 BX001834), and the National Institutes of Health (R01 AI24717 & U01 AI130830). 1707 ANTI-RNP ANTIBODIES ARE ASSOCIATED WITH THE INTERFERON GENE SIGNATURE BUT NOT COMPLEMENT ACTIVATION IN SLE Erika Hubbard*, David S Pisetsky, Peter Lipsky. AMPEL BioSolutions, LLC and RILITE Foundation, Charlottesville, VA, USA; Duke University Medical Center, Durham, NC, USA; VA Medical Center, Durham, NC, USA 10.1136/lupus-2021-lupus21century.102 Background Anti-nuclear antibodies are essential features of SLE and are important markers for both diagnosis and pathogenesis. Anti-double stranded DNA (dsDNA) antibodies, which are routinely monitored to assess disease activity, can form immune complexes that activate complement (C) and promote renal pathology. Relatively less is known about the roles of autoantibodies against RNA binding proteins (RBPs) in pathogenesis and about the relationship between antidsDNA, anti-RBPs, complement activation, and expression of the interferon (IFN) gene signature (IGS). Analysis of data from two clinical trials of tabalumab in SLE (Illuminate 1 & 2, GSE88884) was undertaken to understand these interrelationships. Methods Microarray data from 1620 active (SLEDAI 6), female SLE patients and accompanying laboratory measurements were analyzed. Gene set variation analysis (GSVA) determined enrichment of transcriptomic signatures in each patient. Linear regression analysis was used to determine relationships between IGS GSVA scores and C3 and/or C4 levels as well as autoantibody levels. Unbiased classification and regres","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"36 6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129688440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Y. Becker, E. Rollet-Labelle, Tania Lévesque, J. Leclerc, A. Julien, P. Fortin, É. Boilard
{"title":"1708 Preliminary data on the mapping of anti-mitochondrial antibodies in systemic lupus erythematosus","authors":"Y. Becker, E. Rollet-Labelle, Tania Lévesque, J. Leclerc, A. Julien, P. Fortin, É. Boilard","doi":"10.1136/lupus-2021-lupus21century.103","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.103","url":null,"abstract":"","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130009505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Viktoryia Laurynenka, Li-li Ding, L. Kottyan, M. Weirauch, K. Kaufman, J. James, J. Harley
{"title":"1706 A model of lupus pathogenesis: anti-EBNA1 heteroantibodies initiate lupus by cross reacting with lupus autoantigens, resulting in lupus autoantibodies and clinical disease","authors":"Viktoryia Laurynenka, Li-li Ding, L. Kottyan, M. Weirauch, K. Kaufman, J. James, J. Harley","doi":"10.1136/lupus-2021-lupus21century.101","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.101","url":null,"abstract":"","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116395471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Castrillon, Léa Simoni, T. Broek, C. Poel, E. Akama‐Garren, M. Carroll
{"title":"1702 Comparison of the B cell response to self- versus foreign- antigen in mice revealed by single cell transcriptomics","authors":"C. Castrillon, Léa Simoni, T. Broek, C. Poel, E. Akama‐Garren, M. Carroll","doi":"10.1136/lupus-2021-lupus21century.97","DOIUrl":"https://doi.org/10.1136/lupus-2021-lupus21century.97","url":null,"abstract":"","PeriodicalId":235290,"journal":{"name":"1700 – B cells and autoantibodies","volume":"144 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2021-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"132641271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}