Neuronal surface antigen-specific immunostaining pattern on a rat brain immunohistochemistry in autoimmune...

Area of Science:

• Neuroimmunology
• Autoimmune Encephalitis Diagnostics
• Antibody-Based Biomarkers

Background:

• Autoimmune encephalitis (AE) is associated with various neuronal surface (NS) antibodies (NS-Ab).
• Tissue-based assays (TBA), including rodent brain immunohistochemistry (IHC), are crucial for screening NS-Ab and cell-based assays (CBA) for NS antigen determination.
• The clinical relevance and detailed immunostaining patterns of NS antigens in commercial IHC assays require further investigation.

Purpose of the Study:

• To evaluate the predictive value of "neuropil pattern" and "GFAP pattern" in commercial IHC for NS-Ab detection in 261 patients.
• To characterize the specific immunostaining patterns of seven NS antigens: NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, and GluK2.
• To assess the utility of TBA in screening for NS-Ab and GFAP-Ab and estimating NS antigens.

Main Methods:

• Retrospective analysis of 261 patients' sera using commercial rat brain IHC to assess "neuropil" and "GFAP" patterns.
• Correlation of IHC patterns with results from cell-based assays (CBA) for antibody detection.
• Detailed characterization of immunostaining patterns for seven specific NS antigens (NMDAR, LGI1, GABAaR, GABAbR, AMPAR, Caspr2, GluK2) using TBA.

Main Results:

• The "neuropil pattern" demonstrated high specificity (98.2%) but moderate sensitivity (66.0%) for predicting NS-Ab, with a significant false-negative rate (34.0%) particularly for low-titer NMDAR antibodies.
• False-positive "neuropil-like" staining was attributed to high titers of GAD65-Ab.
• GFAP or GFAP-mimicking patterns were observed in 9.6% of patients, with GFAP-Ab confirmed in 21 of 31 examined patients.
• Distinct immunostaining patterns were identified for each NS antigen, aiding in antigen-specific identification.

Conclusions:

• Commercial IHC is valuable for screening NS-Ab and GFAP-Ab and estimating NS antigens in AE.
• The "neuropil pattern" in commercial IHC is highly specific but may miss low-titer NS-Ab, requiring cautious interpretation of negative results.
• Characterizing antigen-specific immunoreactivity patterns using TBA is a useful biomarker for diagnosing AE.