title: Consumption of erythrocyte CR1 (CD35) is associated with protection against systemic lupus erythematosus renal flare.
abstract: Erythrocyte complement receptor type one (E-CR1) is thought to protect against immune complex (IC) disease through interactions that lead to E-CR1 consumption, and low E-CR1 levels are characteristic of systemic lupus erythematosus (SLE). The purpose of this study was to test the hypothesis that E-CR1 consumption can predict or mark SLE flare. Recurrently active SLE patients [n = 43; 28 with past or present major renal manifestations (SLER) and 15 without (SLENR)], were evaluated every 2 months by detailed protocol testing (mean follow-up 22 months), including direct measurements of E-CR1 levels using a radioimmunoassay. In all patients, detectable E-CR1 levels fluctuated widely through acute periods of consumption and regeneration, preventing the use of any single value as a baseline. However, when individual chronic baseline values were used, determined as the mean of all E-CR1 values 4 months or more from a flare, a clear trend was observed. In 16 of 16 instances of non-renal flare in SLER patients, E-CR1 levels decreased at flare (mean decrease 34%, P < 0.0001). In contrast, no consistent difference was observed for flare in SLENR patients or for renal flare in SLER patients. Changes in E-CR1 levels did not correlate with plasma CR1 levels. In conclusion, single occurrences of E-CR1 consumption did not generally predict or mark SLE flare. However, compared to the average E-CR1 levels measured during no-flare intervals, E-CR1 consumption in SLER patients at flare was strongly associated with freedom from signs of renal involvement. We postulate that E-CR1 consumption reflects E-CR1 function that includes protecting against SLE nephritis.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, The Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH 43210, USA. dan.birmingham@osumc.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Birmingham
authors.forename: K F
authors.initials: KF
authors.lastname: Gavit
authors.forename: S M
authors.initials: SM
authors.lastname: McCarty
authors.forename: C Y
authors.initials: CY
authors.lastname: Yu
authors.forename: B H
authors.initials: BH
authors.lastname: Rovin
authors.forename: H N
authors.initials: HN
authors.lastname: Nagaraja
authors.forename: L A
authors.initials: LA
authors.lastname: Hebert
mesh_terms: D003176:Complement C3 / Q000032:analysis; D003181:Complement C4 / Q000032:analysis; D004912:Erythrocytes / Q000276:immunology*; D005260:Female; D006801:Humans; D007668:Kidney / Q000276:immunology; D008137:Longitudinal Studies; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology*; D008181:Lupus Nephritis / Q000097:blood / Q000276:immunology; D008297:Male; D011446:Prospective Studies; D017463:Receptors, Complement 3b / Q000097:blood / Q000276:immunology*
chemical_list: D003176:Complement C3; D003181:Complement C4; D017463:Receptors, Complement 3b