- Pooled IVIg and SCIg frequently produce positive neuronal LIA results at physiological 10 g/L, whereas manufacturer dilutions commonly abrogate these positives.
- Neuronal tissue IIF yielded non-specific staining for all products at manufacturer dilution and 88% at 10 g/L, with no correlation to LIA or GAD65 ELISA.
- GAD65 ELISA titres were elevated in all Ig preparations; three patients seroconverted after IVIg, underscoring need for cautious post-Ig result interpretation.
Pathology. 2026 Sep 9:S0031-3025(26)00638-0. doi: 10.1016/j.pathol.2026.08.003. Online ahead of print.
ABSTRACT
Immunoglobulin (Ig) products are prescribed for the treatment of a range of immune-mediated disorders, including autoimmune neurological disease. Both intravenous immunoglobulin (IVIg) and subcutaneous immunoglobulin (SCIg) formulations are available. While Ig products can interfere with immunoassay result interpretation, their influence on neuronal antibody screening methods specifically is unknown. Twenty-five Ig products were sourced and processed at 10 g/L to reflect physiological IgG levels, with these preparations then subjected to the manufacturer-recommended dilution protocols for neuronal line immunoassay (LIA), neuronal tissue indirect immunofluorescence (IIF) and glutamic acid decarboxylase (GAD) 65 enzyme-linked immunosorbent assay (ELISA). To provide clinical context, three cases are illustrated, specifically for GAD65 ELISA and Ig interference. Both IVIg and SCIg demonstrated variable positivity across neuronal LIA, tissue IIF and GAD65 ELISA. At 10 g/L, 16 of 25 (64%) products were positive by neuronal LIA, with a median signal intensity of 19 (1+), whereas no products were positive at the manufacturer-recommended dilution. In six individual batches, a reproducible antibody profile was observed (GAD65, CV2/CRMP5, Titin, Zic4). Positive neuronal tissue IIF staining was observed for all Ig products at the manufacturer-recommended dilution and for 22 of 25 (88%) of products at 10 g/L; however, the patterns were non-specific and showed no correlation with LIA or GAD65 ELISA results. On average, GAD65 ELISA titres were elevated for all Ig products: 200.5 IU/mL at 10 g/L and 441.4 IU/mL for neat preparations. Three patients developed positive GAD65 ELISA results after IVIg, having previously shown no detectable titres. Immunoglobulin-related assay interference was observed under experimental conditions, with variations likely attributable to pooled donor Ig, product matrices and the working dilution. Under routine concentrations, the diagnostic applicability of these findings varied by assay. Collectively, these findings highlight the need for cautious interpretation of results if performed after the administration of Ig products.
PMID:42859103 | DOI:10.1016/j.pathol.2026.08.003
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