Binding of complement component C1q to anti-beta2 glycoprotein I antibodies from patients with antiphospholipid syndrome.
OBJECTIVE
To determine if anti-beta2 GPI reactive with surface-bound beta2 GPI can bind C1q, i. e. to determine whether surface-bound beta2 GPI-anti-beta2 GPI immune complexes can initiate the classical pathway of complement activation.


METHODS
Beta2 GPI was bound to chemically-activated microtiter plates which had previously been shown to promote anti-beta2 GPI reactivity with bound beta2 GPI. Wells with surface-bound beta2 GPI (capped with bovine serum albumin) were then reacted with complement-inactivated sera from antiphospholipid syndrome patients (APS) or with control sera. Following removal of unbound serum components, the wells were incubated with biotinylated C1q and probed with peroxidase-conjugated avidin D. Bound C1q was detected at 450 nm using tetramethyl benzidine/peroxidase as a substrate system and expressed as absorbance units (Abs).


RESULTS
The identified 20 APS with elevated anti-beta2 GPI: 4 with IgG only, 4 with IgM only, 1 with IgA only, 1 with IgG and IgA, 6 with IgG and IgM and 4 with IgG, IgA and IgM. C1q binding from 20 healthy controls was 0.039 +/- 0.029 (SD). Of the APS, 17/20 (85%) had Abs >5 SD above controls. The 3 APS with C1q Abs within normal limits had, respectively, IgM only (1), IgA only (1), and both IgG and IgM (1). Statistical analyses (Kruskal-Wallis followed by Dunn's post test) suggest differences in IgG and IgG + IgM groups compared to con (Kruskal-Wallis: p = 0.0002; Dunn's: con vs. IgG, p < 0.05; con vs. IgG + IgM, p < 0.01).


CONCLUSIONS
Anti-beta2 GPI from APS appear to have a variable degree of C1q affinity. Those patients with strong C1q binding responses are likely to have an inflammatory component to their disease processes.
Odorczuk
M
M
Laboratory of Experimental Medicine, St. Joseph's Hospital and Medical Center, Paterson, NJ 07503, USA.
Keil
L B
LB
DeBari
V A
VA
D000936:Antigen-Antibody Complex / Q000378:metabolism; D016736:Antiphospholipid Syndrome / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D001323:Autoantibodies / Q000097:blood / Q000276:immunology / Q000378:metabolism*; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D003171:Complement Pathway, Classical / Q000276:immunology; D006023:Glycoproteins / Q000097:blood / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007074:Immunoglobulin G / Q000378:metabolism; D007249:Inflammation / Q000276:immunology; D008562:Membrane Glycoproteins / Q000097:blood / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding / Q000276:immunology / Q000502:physiology; D053482:beta 2-Glycoprotein I
D000936:Antigen-Antibody Complex; D001323:Autoantibodies; D006023:Glycoproteins; D007074:Immunoglobulin G; D008562:Membrane Glycoproteins; D053482:beta 2-Glycoprotein I; D015922:Complement C1q