Rheumatoid factor testing detects autoantibodies directed against which portion of immunoglobulin G?

• A. RF detects antibodies against the Fab portion of IgG.
• B. RF detects antibodies against immune complexes in joints.
• C. RF detects autoantibodies against the Fc portion of IgG (often IgM type).
• D. RF detects antibodies against citrullinated peptides.

Answer: (C)

Rheumatoid factor testing looks for autoantibodies that bind to the Fc region of IgG. The classic RF is an IgM antibody directed against the Fc fragment of IgG, the constant tail region, not the antigen-binding Fab portion. This binding to IgG's Fc can promote immune complex formation and inflammation in joints, which is why RF is associated with rheumatoid arthritis. It’s important to note that RF is not specific for RA and can be seen in other conditions and even in some healthy individuals. The Fc region target is what makes this test distinct from antibodies against the Fab region or against citrullinated peptides.