TY - JOUR
T1 - Autoimmune central nervous system disorders
T2 - Antibody testing and its clinical utility
AU - Gilligan, Michael
AU - McGuigan, Christopher
AU - McKeon, Andrew
N1 - Publisher Copyright:
© 2024
PY - 2024/4
Y1 - 2024/4
N2 - A rapidly expanding repertoire of neural antibody biomarkers exists for autoimmune central nervous system (CNS) disorders. Following clinical recognition of an autoimmune CNS disorder, the detection of a neural antibody facilitates diagnosis and informs prognosis and management. This review considers the phenotypes, diagnostic assay methodologies, and clinical utility of neural antibodies in autoimmune CNS disorders. Autoimmune CNS disorders may present with a diverse range of clinical features. Clinical phenotype should inform the neural antibodies selected for testing via the use of phenotype-specific panels. Both serum and cerebrospinal fluid (CSF) are preferred in the vast majority of cases but for some analytes either CSF (e.g. N-methyl-D-aspartate receptor [NMDA-R] IgG) or serum (e.g. aquaporin-4 [AQP4] IgG) specimens may be preferred. Screening using 2 methods is recommended for most analytes, particularly paraneoplastic antibodies. We utilize murine tissue-based indirect immunofluorescence assay (TIFA) with subsequent confirmatory protein-specific testing. The cellular location of the target antigen informs choice of confirmatory diagnostic assay (e.g. blot for intracellular antigens such as Hu; cell-based assay for cell surface targets such as leucine-rich glioma inactivated 1 [LGI1]). Titers of positive results have limited diagnostic utility with the exception of glutamic acid decarboxylase (GAD) 65 IgG autoimmunity, which is associated with neurological disease at higher values. While novel antibodies are typically discovered using established techniques such as TIFA and immunoprecipitation-mass spectrometry, more recent high-throughput molecular technologies (such as protein microarray and phage-display immunoprecipitation sequencing) may expedite the process of antibody discovery. Individual neural antibodies inform the clinician regarding the clinical associations, oncological risk stratification and tumor histology, the likely prognosis, and immunotherapy choice. In the era of neural antibody biomarkers for autoimmune CNS disorders, access to appropriate laboratory assays for neural antibodies is of critical importance in the diagnosis and management of these disorders.
AB - A rapidly expanding repertoire of neural antibody biomarkers exists for autoimmune central nervous system (CNS) disorders. Following clinical recognition of an autoimmune CNS disorder, the detection of a neural antibody facilitates diagnosis and informs prognosis and management. This review considers the phenotypes, diagnostic assay methodologies, and clinical utility of neural antibodies in autoimmune CNS disorders. Autoimmune CNS disorders may present with a diverse range of clinical features. Clinical phenotype should inform the neural antibodies selected for testing via the use of phenotype-specific panels. Both serum and cerebrospinal fluid (CSF) are preferred in the vast majority of cases but for some analytes either CSF (e.g. N-methyl-D-aspartate receptor [NMDA-R] IgG) or serum (e.g. aquaporin-4 [AQP4] IgG) specimens may be preferred. Screening using 2 methods is recommended for most analytes, particularly paraneoplastic antibodies. We utilize murine tissue-based indirect immunofluorescence assay (TIFA) with subsequent confirmatory protein-specific testing. The cellular location of the target antigen informs choice of confirmatory diagnostic assay (e.g. blot for intracellular antigens such as Hu; cell-based assay for cell surface targets such as leucine-rich glioma inactivated 1 [LGI1]). Titers of positive results have limited diagnostic utility with the exception of glutamic acid decarboxylase (GAD) 65 IgG autoimmunity, which is associated with neurological disease at higher values. While novel antibodies are typically discovered using established techniques such as TIFA and immunoprecipitation-mass spectrometry, more recent high-throughput molecular technologies (such as protein microarray and phage-display immunoprecipitation sequencing) may expedite the process of antibody discovery. Individual neural antibodies inform the clinician regarding the clinical associations, oncological risk stratification and tumor histology, the likely prognosis, and immunotherapy choice. In the era of neural antibody biomarkers for autoimmune CNS disorders, access to appropriate laboratory assays for neural antibodies is of critical importance in the diagnosis and management of these disorders.
KW - Antibody panels
KW - Autoimmune central nervous system disorders
KW - Autoimmune neurology
KW - Neural antibody testing
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U2 - 10.1016/j.clinbiochem.2024.110746
DO - 10.1016/j.clinbiochem.2024.110746
M3 - Review article
C2 - 38462203
AN - SCOPUS:85188058487
SN - 0009-9120
VL - 126
JO - Clinical Biochemistry
JF - Clinical Biochemistry
M1 - 110746
ER -