Open AccessSystemic lupus erythematosus serum deposits C4d on red blood cells, decreases red blood cell membrane deformability, and promotes nitric oxide production
Author(s) -
Ghiran Ionita C.,
Zeidel Mark L.,
Shevkoplyas Sergey S.,
Burns Jennie M.,
Tsokos George C.,
Kyttaris Vasileios C.
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30143
Subject(s) - red blood cell , flow cytometry , complement system , nitric oxide , chemistry , erythrocyte deformability , incubation , band 3 , lupus erythematosus , complement membrane attack complex , immunology , phosphorylation , microbiology and biotechnology , membrane , biology , biochemistry , immune system , membrane protein , antibody , organic chemistry
Abstract Objective Systemic lupus erythematosus (SLE) is characterized by intravascular activation of the complement system and deposition of complement fragments (C3 and C4) on plasma membranes of circulating cells, including red blood cells (RBCs). The aim of this study was to address whether this process affects the biophysical properties of RBCs. Methods Serum and RBCs were isolated from patients with SLE and healthy controls. RBCs from healthy universal donors (type O, Rh negative) were incubated with SLE or control serum. We used flow cytometry to assess complement fragment deposition on RBCs. RBC membrane deformability was measured using 2‐dimensional microchannel arrays. Protein phosphorylation levels were quantified by Western blotting. Results Incubation of healthy universal donor RBCs with sera from patients with SLE, but not with control sera, led to deposition of C4d fragments on the RBCs. Complement‐decorated RBCs exhibited significant decreases in both membrane deformability and flickering. Sera from SLE patients triggered a transitory Ca ++ influx in RBCs that was associated with decreased phosphorylation of β‐spectrin and with increased phosphorylation of band 3, two key proteins of RBC cytoskeleton. Finally, incubation with SLE sera led to the production of nitric oxide by RBCs, whereas this did not occur with control sera. Conclusion Our data suggest that complement activation in patients with SLE leads to calcium‐dependent cytosketeletal changes in RBCs that render them less deformable, probably impairing their flow through capillaries. This phenomenon may negatively affect the delivery of oxygen to the tissues.