{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T09:33:26Z","timestamp":1771234406319,"version":"3.50.1"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2020,7,1]],"date-time":"2020-07-01T00:00:00Z","timestamp":1593561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100007820","name":"Alliance for Lupus Research","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007820","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,7,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Our recent study has implicated bradykinin (BK) signaling as being of pathogenic importance in lupus. This study aims to investigate the biomarker potential of BK peptides, BK and BK-des-arg-9, in lupus and other rheumatic autoimmune diseases. Sera from systemic lupus erythematosus (SLE) patients and healthy subjects were screened for BK and BK-des-arg-9 by liquid chromatography\u2013mass spectrometry metabolomics. Serum from 6-mo-old C57BL\/6 mice and three murine lupus strains were also screened for the two peptides by metabolomics. Given the promising initial screening results, validation of these two peptides was next conducted using multiple reaction monitoring in larger patient cohorts. In initial metabolomics screening, BK-des-arg-9 was 22-fold higher in SLE serum and 106-fold higher in mouse lupus serum compared with healthy controls. In validation assays using multiple reaction monitoring and quadrupole time-of-flight mass spectrometry, BK and BK-des-arg-9 showed significant elevations in SLE serum compared with controls (p &amp;lt; 0.0001; area under the curve = 0.79\u20130.88), with a similar but less pronounced increase being noted in rheumatoid arthritis serum. Interestingly, increased renal SLE disease activity index in lupus patients was associated with reduced circulating BK-des-arg-9, and the reasons for this remain to be explored. To sum, increased conversion of BK to the proinflammatory metabolite BK-des-arg-9 appears to be a common theme in systemic rheumatic diseases. Besides serving as an early marker for systemic autoimmunity, independent studies also show that this metabolic axis may also be a pathogenic driver and therapeutic target in lupus.<\/jats:p>","DOI":"10.4049\/jimmunol.1801167","type":"journal-article","created":{"date-parts":[[2020,6,15]],"date-time":"2020-06-15T19:45:11Z","timestamp":1592250311000},"page":"369-376","source":"Crossref","is-referenced-by-count":15,"title":["Upregulation of Proinflammatory Bradykinin Peptides in Systemic Lupus Erythematosus and Rheumatoid Arthritis"],"prefix":"10.1093","volume":"205","author":[{"given":"Kamala","family":"Vanarsa","sequence":"first","affiliation":[{"name":"Biomedical Engineering, University of Houston , Houston, TX 77204"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-5234","authenticated-orcid":false,"given":"Jared","family":"Henderson","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of Houston , Houston, TX 77204"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8729-4897","authenticated-orcid":false,"given":"Sanam","family":"Soomro","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of Houston , Houston, TX 77204"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Qin","sequence":"additional","affiliation":[{"name":"Tongji University School of Medicine, Shanghai Tenth People\u2019s Hospital , Shanghai 200072 ,","place":["People\u2019s Republic of China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ting","family":"Zhang","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of Houston , Houston, TX 77204"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Jordan","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Albert Einstein College of Medicine , Bronx, NY 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3204-6068","authenticated-orcid":false,"given":"Chaim","family":"Putterman","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Albert Einstein College of Medicine , Bronx, NY 10461"},{"name":"Azrieli Faculty of Medicine, Bar-Ilan University , Zefat, Israel 52000"},{"name":"Research Institute, Galilee Medical Center , Nahariya, Israel 22100"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8540-1289","authenticated-orcid":false,"given":"Irene","family":"Blanco","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Albert Einstein College of Medicine , Bronx, NY 10461"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ramesh","family":"Saxena","sequence":"additional","affiliation":[{"name":"Nephrology Clinical and Translational Research, University of Texas Southwestern Medical Center , Dallas, TX 75390"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandra","family":"Mohan","sequence":"additional","affiliation":[{"name":"Biomedical Engineering, University of Houston , Houston, TX 77204"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,7,15]]},"reference":[{"key":"2025030417504342800_r1","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.bone.2008.02.003","article-title":"Kinin B1 and B2 receptor expression in osteoblasts and fibroblasts is enhanced by interleukin-1 and tumour necrosis factor-alpha. 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