Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder affecting
the joints. Many patients carry anti-citrullinated protein autoantibodies (ACPA).
Overactivation of the complement system seems to be part of the pathogenesis of RA,
and autoantibodies against the pathway initiators C1q and MBL, and the regulator of
the complement alternative pathway, factor H (FH), were previously reported. Our aim
was to analyze the presence and role of autoantibodies against complement proteins
in a Hungarian RA cohort. To this end, serum samples of 97 ACPA-positive RA patients
and 117 healthy controls were analyzed for autoantibodies against FH, factor B (FB),
C3b, C3-convertase (C3bBbP), C1q, MBL and factor I. In this cohort, we did not detect
any patient with FH autoantibodies but detected C1q autoantibodies in four patients,
MBL autoantibodies in two patients and FB autoantibodies in five patients. Since the
latter autoantibodies were previously reported in patients with kidney diseases but
not in RA, we set out to further characterize such FB autoantibodies. The isotypes
of the analyzed autoantibodies were IgG2, IgG3, IgGκ, IgGλ and their binding site
was localized in the Bb part of FB. We detected in vivo formed FB–autoanti-FB complexes
by Western blot. The effect of the autoantibodies on the formation, activity and FH-mediated
decay of the C3 convertase in solid phase convertase assays was determined. In order
to investigate the effect of the autoantibodies on complement functions, hemolysis
assays and fluid phase complement activation assays were performed. The autoantibodies
partially inhibited the complement-mediated hemolysis of rabbit red blood cells, inhibited
the activity of the solid phase C3-convertase and C3 and C5b-9 deposition on complement
activating surfaces. In summary, in ACPA-positive RA patients we identified FB autoantibodies.
The characterized FB autoantibodies did not enhance complement activation, rather,
they had inhibitory effect on complement. These results support the involvement of
the complement system in the pathomechanism of RA and raise the possibility that protective
autoantibodies may be generated in some patients against the alternative pathway C3
convertase. However, further analyses are needed to assess the exact role of such
autoantibodies.
