Cell-bound complement activation products in systemic lupus erythematosus: comparison with anti-double-stranded DNA and standard complement measurements.
OBJECTIVE
To compare the performance characteristics of cell-bound complement (C4d) activation products (CBCAPS) on erythrocyte (EC4d) and B cells (BC4d) with antibodies to double-stranded DNA (anti-dsDNA) and complement C3 and C4 in systemic lupus erythematosus (SLE).


METHODS
The study enrolled 794 subjects consisting of 304 SLE and a control group consisting of 285 patients with other rheumatic diseases and 205 normal individuals. Anti-dsDNA and other autoantibodies were measured using solid-phase immunoassays while EC4d and BC4d were determined using flow cytometry. Complement proteins were determined using immunoturbidimetry. Disease activity in SLE was determined using a non-serological Systemic Lupus Erythematosus Disease Activity Index SELENA Modification. A two-tiered methodology combining CBCAPS with autoantibodies to cellular and citrullinated antigens was also developed. Statistical analyses used area under receiver operating characteristic curves and calculations of area under the curve (AUC), sensitivity and specificity.


RESULTS
AUC for EC4d (0.82±0.02) and BC4d (0.84±0.02) was higher than those yielded by C3 (0.73±0.02) and C4 (0.72±0.02) (p<0.01). AUC for CBCAPS was also higher than the AUC yielded by anti-dsDNA (0.79±0.02), but significance was only achieved for BC4d (p<0.01). The combination of EC4d and BC4d in multivariate testing methodology with anti-dsDNA and autoantibodies to cellular and citrullinated antigens yielded 80% sensitivity for SLE and specificity ranging from 70% (Sjogren's syndrome) to 92% (rheumatoid arthritis) (98% vs. normal). A higher proportion of patients with SLE with higher levels of disease activity tested positive for elevated CBCAPS, reduced complement and anti-dsDNA (p<0.03).


CONCLUSIONS
CBCAPS have higher sensitivity than standard complement and anti-dsDNA measurements, and may help with the differential diagnosis of SLE in combination with other autoantibodies.
Albert Einstein College of Medicine and Montefiore Medical Center , Bronx, New York , USA.
Chaim
C
Putterman
Hofstra North Shore-Long Island Jewish School of Medicine , Chicago, Illinois , USA.
Richard
R
Furie
Northwestern University Feinberg School of Medicine , Chicago, Illinois , USA.
Rosalind
R
Ramsey-Goldman
NYU School of Medicine , New York, New York , USA.
Anca
A
Askanase
NYU School of Medicine , New York, New York , USA.
Jill
J
Buyon
UCSD School of Medicine , La Jolla, California , USA.
Kenneth
K
Kalunian
UAB School of Medicine Birmingham , Birmingham, Alabama , USA.
W Winn
WW
Chatham
Brigham and Women's Hospital , Boston, Massachusetts , USA.
Elena
E
Massarotti
Hospital for Special Surgery , New York, New York , USA.
Kyriakos
K
Kirou
Albert Einstein College of Medicine and Montefiore Medical Center , Bronx, New York , USA.
Nicole
N
Jordan
Albert Einstein College of Medicine and Montefiore Medical Center , Bronx, New York , USA.
Irene
I
Blanco
Washington Hospital Center , Washington, DC , USA.
Arthur
A
Weinstein
San Diego Arthritis Research Clinic , San Diego, California , USA.
Puja
P
Chitkara
Allegheny Health System , Pittsburgh, Pennsylvania , USA.
Susan
S
Manzi
Allegheny Health System , Pittsburgh, Pennsylvania , USA.
Joseph
J
Ahearn
Exagen Diagnostics , Vista, California , USA.
Tyler
T
O'Malley
Exagen Diagnostics , Vista, California , USA.
John
J
Conklin
Exagen Diagnostics , Vista, California , USA.
Claudia
C
Ibarra
Exagen Diagnostics , Vista, California , USA.
Derren
D
Barken
Exagen Diagnostics , Vista, California , USA.
Thierry
T
Dervieux
Autoantibodies; Autoimmune Diseases; Systemic Lupus Erythematosus