Autoantibodies against complement factor B in rheumatoid arthritis.

Area of Science:

• Immunology
• Rheumatology
• Biochemistry

Background:

• Rheumatoid arthritis (RA) is an autoimmune disease characterized by joint inflammation.
• The complement system's overactivation is implicated in RA pathogenesis.
• Previous studies reported autoantibodies against complement components like C1q, MBL, and factor H (FH) in RA.

Purpose of the Study:

• To investigate the presence and role of autoantibodies against complement proteins in a Hungarian RA cohort.
• To characterize autoantibodies against factor B (FB), a complement regulator, in ACPA-positive RA patients.

Main Methods:

• Serum samples from 97 ACPA-positive RA patients and 117 healthy controls were analyzed for autoantibodies against complement proteins.
• Western blot was used to detect in vivo formed FB-autoanti-FB complexes.
• Complement assays (hemolysis, fluid phase activation, solid phase convertase) were performed to assess the functional impact of FB autoantibodies.

Main Results:

• Autoantibodies against C1q, MBL, and FB were detected in a subset of RA patients.
• FB autoantibodies, primarily IgG isotypes binding to the Bb region, were identified in five RA patients.
• These FB autoantibodies demonstrated inhibitory effects on complement-mediated hemolysis and C3-convertase activity, and reduced C3 and C5b-9 deposition.

Conclusions:

• The study identified FB autoantibodies in ACPA-positive RA patients.
• These autoantibodies appear to inhibit, rather than enhance, complement activation.
• The findings suggest a potential protective role for these autoantibodies against complement overactivation in RA, warranting further investigation.