Anti-GAD65 autoantibody levels measured by ELISA and alternative types of immunoassays in relation to neuropsychiatric diseases versus diabetes mellitus type 1.

Autor: Zong S; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands., Vinke AM; Department of Neurology, Maastricht University Medical Center (MUMC +), Maastricht, Netherlands., Du P; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands., Hoffmann C; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands.; Algarve Biomedical Center, Algarve Biomedical Center Research Institute, Faro, Portugal., Mané-Damas M; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands., Molenaar PC; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands., Damoiseaux JGMC; Central Diagnostic Laboratory, MUMC+, Maastricht, Netherlands., Losen M; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands., Rouhl RPW; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands.; Department of Neurology, Maastricht University Medical Center (MUMC +), Maastricht, Netherlands.; Academic Centre for Epileptology Kempenhaeghe/MUMC+, Maastricht, Netherlands., Martinez-Martinez P; Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNS), Maastricht University, Maastricht, Netherlands.
Jazyk: angličtina
Zdroj: Frontiers in neurology [Front Neurol] 2023 May 25; Vol. 14, pp. 1111063. Date of Electronic Publication: 2023 May 25 (Print Publication: 2023).
DOI: 10.3389/fneur.2023.1111063
Abstrakt: Background: Anti-GAD65 autoantibodies (GAD65-Abs) may occur in patients with epilepsy and other neurological disorders, but the clinical significance is not clear-cut. Whereas high levels of GAD65-Abs are considered pathogenic in neuropsychiatric disorders, low or moderate levels are only considered as mere bystanders in, e.g., diabetes mellitus type 1 (DM1). The value of cell-based assays (CBA) and immunohistochemistry (IHC) for GAD65-Abs detection has not been clearly evaluated in this context.
Objective: To re-evaluate the assumption that high levels of GAD65-Abs are related to neuropsychiatric disorders and lower levels only to DM1 and to compare ELISA results with CBA and IHC to determine the additional value of these tests.
Methods: 111 sera previously assessed for GAD65-Abs by ELISA in routine clinical practice were studied. Clinical indications for testing were, e.g., suspected autoimmune encephalitis or epilepsy (neuropsychiatric cohort; n  = 71, 7 cases were initially tested positive for GAD65-Abs by ELISA), and DM1 or latent autoimmune diabetes in adults (DM1/LADA cohort ( n  = 40, all were initially tested positive)). Sera were re-tested for GAD65-Abs by ELISA, CBA, and IHC. Also, we examined the possible presence of GAD67-Abs by CBA and of other neuronal autoantibodies by IHC. Samples that showed IHC patterns different from GAD65 were further tested by selected CBAs.
Results: ELISA retested GAD65-Abs level in patients with neuropsychiatric diseases was higher than in patients with DM1/LADA (only retested positive samples were compared; 6 vs. 38; median 47,092 U/mL vs. 581 U/mL; p  = 0.02). GAD-Abs showed positive both by CBA and IHC only if antibody levels were above 10,000 U/mL, without a difference in prevalence between the studied cohorts. We found other neuronal antibodies in one patient with epilepsy (mGluR1-Abs, GAD-Abs negative), and in a patient with encephalitis, and two patients with LADA.
Conclusion: GAD65-Abs levels are significantly higher in patients with neuropsychiatric disease than in patients with DM1/LADA, however, positivity in CBA and IHC only correlates with high levels of GAD65-Abs, and not with the underlying diseases.
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2023 Zong, Vinke, Du, Hoffmann, Mané-Damas, Molenaar, Damoiseaux, Losen, Rouhl and Martinez-Martinez.)
Databáze: MEDLINE