Our study objective was testing for anti-neuronal
autoantibodies within commercially available
intravenous immunoglobulin (
IVIg) preparations. Sixteen samples from 5 different commercially available
IVIg preparations were tested with cell-based assays (CBA) and
enzyme-linked
immunosorbent assay (ELISA) to detect and characterize common neuronal
autoantibodies, and with immunohistochemistry on teased fibers from mouse sciatic nerve and on mouse brain sections to screen for nodal and not yet identified neuronal
antigens. In 15/16
IVIg preparations, anti-GAD
antibodies were detected in titers ranging from 40 to 1507 IU/mL, as typically seen in
type 1 diabetes, but not in the range (> 2000 IU/mL) seen in GAD-positive neurological patients. None of the preparations was however positive with anti-GAD CBA.
Antibodies to AQP4 were also detected by ELISA in 15/16
IVIg preparations with titers comparable to those seen in AQP4-seropositive NMO patients; with CBA, however, all
IVIg samples were AQP4-negative.
IVIg preparations contained
IgG-anti-MAG
antibodies by ELISA at statistically significant higher titers compared to controls. Two of the 16
IVIg samples were positive for human
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)
antibodies. All
IVIg preparations were negative for
antibodies to MOG, NMDAR, anti-nodal, and other neuronal-specific
proteins.
IVIg preparations contain
antibodies against GAD and AQP4 in titers comparable to those seen in autoimmune patients when tested by ELISA, but not by CBA or tissue immunohistochemistry, suggesting that the
autoantibodies within the
IVIg are against linear rather than structural
epitopes, as part of the natural antibody immune repertoire. The information is clinically important for diagnosis when testing patients' sera after they have received
therapy with
IVIg to avoid false interpretation.