OBJECTIVE: C4-derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte-bound C4 (E-C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement-bearing immune complexes via erythrocytes expressing complement receptor 1 (CR1). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E-C4 and E-CR1 expression on erythrocytes of patients with SLE. METHODS: We conducted a cross-sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1. RESULTS: Patients with SLE had higher levels of E-C4d and lower levels of E-CR1 than did patients with other diseases (P < or = 0.001) or healthy controls (P < or = 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%. CONCLUSION: This is the first report of abnormal levels of E-C4d in human disease. We found that abnormally high levels of E-C4d and low levels of E-CR1 are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E-C4d/E-CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis.
OBJECTIVE: C4-derived activation fragments are the only complement ligands present on the surfaces of normal erythrocytes. The significance of this observation is unknown, and the role of erythrocyte-bound C4 (E-C4) in human disease has not been explored. More than any other human disease, the pathogenesis of systemic lupus erythematosus (SLE) has been characterized by defects in clearance of complement-bearing immune complexes via erythrocytes expressing complement receptor 1 (CR1). This study was undertaken to determine whether these functional defects might be reflected by abnormal patterns of E-C4 and E-CR1 expression on erythrocytes of patients with SLE. METHODS: We conducted a cross-sectional study of 100 patients with SLE, 133 patients with other diseases, and 84 healthy controls. Erythrocytes were characterized by indirect immunofluorescence and by flow cytometry for determination of levels of C4d and CR1. RESULTS:Patients with SLE had higher levels of E-C4d and lower levels of E-CR1 than did patients with other diseases (P < or = 0.001) or healthy controls (P < or = 0.001). The test was 81% sensitive and 91% specific for SLE versus healthy controls and 72% sensitive and 79% specific for SLE versus other diseases, and it had an overall negative predictive value of 92%. CONCLUSION: This is the first report of abnormal levels of E-C4d in human disease. We found that abnormally high levels of E-C4d and low levels of E-CR1 are characteristic of SLE, and combined measurement of the 2 molecules has high diagnostic sensitivity and specificity for lupus. Determination of E-C4d/E-CR1 levels may be a useful addition to current tests and criteria for SLE diagnosis.
Authors: Ionita C Ghiran; Mark L Zeidel; Sergey S Shevkoplyas; Jennie M Burns; George C Tsokos; Vasileios C Kyttaris Journal: Arthritis Rheum Date: 2011-02
Authors: D J Birmingham; K F Gavit; S M McCarty; C Y Yu; B H Rovin; H N Nagaraja; L A Hebert Journal: Clin Exp Immunol Date: 2006-02 Impact factor: 4.330
Authors: Robert A Cohen; George Bayliss; Jose C Crispin; Gwen F Kane-Wanger; Christine A Van Beek; Vasileios C Kyttaris; Ingrid Avalos; C Yung Yu; George C Tsokos; Isaac E Stillman Journal: Clin Immunol Date: 2008-07 Impact factor: 3.969
Authors: Amy H Kao; Jeannine S Navratil; Margie J Ruffing; Chau-Ching Liu; Douglas Hawkins; Kathleen M McKinnon; Natalya Danchenko; Joseph M Ahearn; Susan Manzi Journal: Arthritis Rheum Date: 2010-03
Authors: Kazi Abdus Salam; Richard Y Wang; Teresa Grandinetti; Valeria De Giorgi; Harvey J Alter; Robert D Allison Journal: Hepatology Date: 2018-11-01 Impact factor: 17.425
Authors: C-H Chen; I Ghiran; F J M Beurskens; G Weaver; J A Vincent; A Nicholson-Weller; L B Klickstein Journal: Clin Exp Immunol Date: 2007-06 Impact factor: 4.330