Human polyreactive IgM monoclonal antibodies with blocking activity against self-reactive IgG

Area of Science:

• Immunology
• Autoimmunity
• Molecular Biology

Background:

• Natural IgM antibodies play a role in controlling IgG reactivity in healthy serum.
• Multispecific IgM monoclonal antibodies (MoAbs) from renal dialysis patients exhibit properties similar to natural polyreactive autoantibodies.

Purpose of the Study:

• To investigate the blocking activity of human IgM monoclonal antibodies (MoAbs) on self-reactive IgG antibodies.
• To determine if these MoAbs can inhibit the binding of disease-associated autoantibodies to specific antigens.

Main Methods:

• Competitive inhibition assays were performed using four human IgM MoAbs.
• The binding of purified IgG from healthy controls, SLE patients, and autoimmune thyroiditis patients to histone, dsDNA, RNP, and thyroglobulin was assessed.
• The interaction mechanism was further investigated using F(ab')2 fragments of autoreactive IgG.

Main Results:

• The IgM MoAbs inhibited the binding of self-reactive IgG to histone and dsDNA, but not to RNP or thyroglobulin.
• This inhibitory effect was dose-dependent and mediated by V-region interactions.
• The MoAbs did not inhibit IgG alloantibody binding to cellular antigens in polytransfused patients.

Conclusions:

• The studied IgM MoAbs demonstrate functional blocking activity against specific autoantibodies.
• These findings support the concept of a functional idiotypic network regulating autoimmune responses.
• The IgM MoAbs may represent natural polyreactive antibodies within a physiological network that neutralizes autoreactive IgG.