Platelet C4d is highly specific for systemic lupus erythematosus.
OBJECTIVE
Complement-activation product C4d is deposited on normal erythrocytes, while abnormal levels have been observed on the surface of erythrocytes of patients with systemic lupus erythematosus (SLE). This study examines whether C4d also deposits on human platelet surfaces, and whether platelet-bound C4d may provide a biomarker for SLE.


METHODS
We conducted a cross-sectional study of 105 patients with SLE, 115 patients with other diseases, and 100 healthy controls. Levels of C4d on the surface of platelets were examined by flow cytometry and scanning confocal microscopy. Statistical analyses were performed to determine the clinical variables associated with platelet C4d.


RESULTS
Abnormal levels of platelet C4d were found to be highly specific for SLE. Platelet C4d was detected in 18% of patients with SLE, being 100% specific for a diagnosis of SLE compared with healthy controls and 98% specific for SLE compared with patients with other diseases (P < 0.0001). In addition, platelet C4d was significantly associated with positivity for lupus anticoagulant (P < 0.0001) and anticardiolipin antibodies of the IgG (P = 0.035) or the IgM (P = 0.016) isotype. Platelet C4d was also significantly associated with SLE disease activity according to the SLE Disease Activity Index (P = 0.039), low serum C4 (P = 0.046), an elevated erythrocyte sedimentation rate (P = 0.006), and abnormal levels of C4d on erythrocytes (P < 0.0001).


CONCLUSIONS
This observation suggests that platelet-bound C4d may be a useful biomarker for SLE and may be a clue to the pathogenic mechanisms responsible for the myriad thrombotic and vascular complications of lupus associated with antiphospholipid antibodies.
Navratil
Jeannine S
JS
University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Manzi
Susan
S
Kao
Amy H
AH
Krishnaswami
Shanthi
S
Liu
Chau-Ching
CC
Ruffing
Margie J
MJ
Shaw
Penny S
PS
Nilson
Abbey C
AC
Dryden
Emily R
ER
Johnson
Jeffrey J
JJ
Ahearn
Joseph M
JM
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000378:metabolism*; D015935:Complement C4b; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000097:blood* / Q000175:diagnosis; D018613:Microscopy, Confocal; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood*
D015415:Biomarkers; D010446:Peptide Fragments; D015935:Complement C4b; C032261:complement C4d