Anti-Neuronal Antibodies Within the IVIg Preparations: Importance in Clinical Practice

Area of Science:

• Neuroimmunology
• Immunology
• Biochemistry

Background:

• Intravenous immunoglobulin (IVIg) is a therapy derived from pooled human plasma.
• Concerns exist regarding potential contamination of IVIg with autoantibodies.
• Neuronal autoantibodies can cause neurological disorders.

Purpose of the Study:

• To investigate the presence and characterization of anti-neuronal autoantibodies in commercial IVIg preparations.
• To determine if detected autoantibodies are against linear or structural epitopes.
• To provide clinically relevant information for interpreting diagnostic tests in patients treated with IVIg.

Main Methods:

• Testing of 16 IVIg samples from 5 commercial preparations.
• Utilized cell-based assays (CBA), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry.
• Screened for antibodies against GAD, AQP4, MAG, HMGCR, MOG, NMDAR, and nodal antigens.

Main Results:

• Anti-GAD and anti-AQP4 antibodies detected by ELISA in most IVIg samples, but negative by CBA.
• Elevated IgG-anti-MAG antibodies found in IVIg compared to controls.
• Two IVIg samples tested positive for anti-HMGCR antibodies.
• All IVIg preparations were negative for anti-MOG, anti-NMDAR, and anti-nodal antibodies.

Conclusions:

• IVIg preparations contain autoantibodies (e.g., anti-GAD, anti-AQP4) that appear to target linear epitopes, not structural ones.
• The presence of these autoantibodies in IVIg can lead to false-positive results in diagnostic assays.
• Clinical interpretation of patient sera tested after IVIg therapy requires careful consideration of these findings.