18 results on '"Zekeridou, Anastasia"'
Search Results
2. Anti-Neuronal Nuclear Antibody 3 Autoimmunity Targets Dachshund Homolog 1.
- Author
-
Zekeridou A, Yang B, Lennon VA, Guo Y, Wu L, Lucchinetti CF, McKeon A, Pittock SJ, and Flanagan EP
- Subjects
- Animals, Female, Humans, Male, Middle Aged, Autoantigens, Biomarkers, Immunoglobulin G, Autoimmunity, Neoplasms
- Abstract
The antigen specificity of Anti-Neuronal Nuclear Antibody-type 3 (ANNA3)-IgG is unknown. We identified Dachshund-homolog 1 (DACH1) as the ANNA3 autoantigen and confirmed it by antigen-specific assays, immunohistochemical colocalization and immune absorption experiments. Patients' median age was 63.5 years (range, 49-88); 67% were female. Neurological manifestations (information available for 30 patients) included one or more of neuropathy, 12; cognitive difficulties, 11; ataxia, 8; dysautonomia, 7. Evidence of a neoplasm was present in 27 of 30 (90%), most of neuroendocrine lineage. DACH1-IgG is rare and represents a novel proposed biomarker of neurological autoimmunity and cancer. ANN NEUROL 2022;91:670-675., (© 2022 American Neurological Association.)
- Published
- 2022
- Full Text
- View/download PDF
3. Synaptic autoimmunity: new insights into LGI1 antibody-mediated neuronal dysfunction.
- Author
-
Zekeridou A and Pittock SJ
- Subjects
- Humans, Intracellular Signaling Peptides and Proteins, Neurons, Synaptic Transmission, Autoantibodies, Autoimmunity
- Published
- 2020
- Full Text
- View/download PDF
4. Phosphodiesterase 10A IgG: A novel biomarker of paraneoplastic neurologic autoimmunity.
- Author
-
Zekeridou A, Kryzer T, Guo Y, Hassan A, Lennon V, Lucchinetti CF, Pittock S, and McKeon A
- Subjects
- Aged, Autoantibodies blood, Autoantibodies cerebrospinal fluid, Basal Ganglia pathology, Biomarkers blood, Biomarkers cerebrospinal fluid, Female, Humans, Magnetic Resonance Imaging, Male, Movement Disorders immunology, Neoplasms immunology, Neuroimaging, Paraneoplastic Syndromes blood, Paraneoplastic Syndromes cerebrospinal fluid, Autoimmunity immunology, Immunoglobulin G blood, Immunoglobulin G cerebrospinal fluid, Paraneoplastic Syndromes immunology, Phosphoric Diester Hydrolases immunology
- Abstract
Objective: To describe a novel antibody biomarker of neurologic paraneoplastic autoimmunity specific for phosphodiesterase 10A (PDE10A), a striatum-enriched phosphodiesterase, and to characterize the clinical phenotype of patients with PDE10A immunoglobulin G (IgG)., Methods: We describe 7 patients with autoantibodies specific for PDE10A identified in the Mayo Clinic Neuroimmunology Laboratory. Patient specimens (sera, 7; CSF, 4) produced identical basal ganglia-predominant synaptic staining of murine brain tissue by indirect immunofluorescence. The autoantigen was identified by immunoprecipitation and mass spectrometry as PDE10A, and confirmed by antigen-specific recombinant Western blot and cell-based assays, and immune absorption experiments., Results: The median patient age was 70 years (range 66-76); 4 were men. Four patients with clinical information available had movement disorders (hyperkinetic in 3 [chorea, ballismus, dystonia] and parkinsonism in 1). All patients but one had cancer (lung [adenocarcinoma 1, squamous cell carcinoma 1, poorly differentiated mesenchymal carcinoma 1], renal adenocarcinoma 2, and pancreatic adenocarcinoma 1). Two of the 7 patients developed hyperkinetic movement disorders during treatment with immune checkpoint inhibitors (nivolumab and pembrolizumab), though none of 26 cancer control patients treated with immune checkpoint inhibitors harbored PDE10A IgG in their serum. MRIs from those 2 patients with hyperkinetic movement disorders demonstrated fluid-attenuated inversion recovery/T2 basal ganglia hyperintensities, and their CSF harbored unique oligoclonal bands. One of those 2 patients had substantial improvement after corticosteroids. One patient's renal adenocarcinoma expressed PDE10A by immunohistochemistry., Conclusions: PDE10A IgG defines a novel rare neurologic autoimmune syndrome and expands the spectrum of diagnosable paraneoplastic CNS disorders. The intracellular location of PDE10A suggests a T-cell-mediated pathology targeting cells displaying MHC1-bound PDE10A peptides., (Copyright © 2019 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)
- Published
- 2019
- Full Text
- View/download PDF
5. LGI1 and CASPR2 neurological autoimmunity in children.
- Author
-
López-Chiriboga AS, Klein C, Zekeridou A, McKeon A, Dubey D, Flanagan EP, Lennon VA, Tillema JM, Wirrell EC, Patterson MC, Gadoth A, Aaen JG, Brenton JN, Bui JD, Moen A, Otten C, Piquet A, and Pittock SJ
- Subjects
- Adolescent, Autoantibodies immunology, Autoantibodies metabolism, Autoimmune Diseases of the Nervous System metabolism, Child, Child, Preschool, Female, Humans, Immunotherapy methods, Intracellular Signaling Peptides and Proteins, Male, Membrane Proteins immunology, Nerve Tissue Proteins immunology, Potassium Channels, Voltage-Gated immunology, Proteins immunology, Autoimmune Diseases of the Nervous System immunology, Autoimmunity immunology, Membrane Proteins metabolism, Nerve Tissue Proteins metabolism, Proteins metabolism
- Abstract
The clinical phenotype of leucine-rich glioma-inactivated protein 1 (LGI1) and contactin-associated proteinlike 2 (CASPR2) autoimmunity is well defined in adults. Data for children are limited (<10 cases). Among 13,319 pediatric patients serologically tested for autoimmune neurological disorders (2010-2017), 264 were seropositive for voltage-gated potassium channel-complex-IgG (radioimmunoprecipitation). Only 13 (4.9%) were positive by transfected cell-binding assay for LGI1-IgG (n = 7), CASPR2-IgG (n = 3), or both (n = 3). This is significantly less than in adults. Encephalopathy, seizures, and peripheral nerve hyperexcitability were common, as was coexisting autoimmunity. No faciobrachial dystonic seizures or cancers were identified. Functional neurologic disorders were frequently the initial diagnosis, and immunotherapy appeared beneficial. Ann Neurol 2018;84:473-480., (© 2018 American Neurological Association.)
- Published
- 2018
- Full Text
- View/download PDF
6. Autoimmune GFAP astrocytopathy: Prospective evaluation of 90 patients in 1 year.
- Author
-
Dubey D, Hinson SR, Jolliffe EA, Zekeridou A, Flanagan EP, Pittock SJ, Basal E, Drubach DA, Lachance DH, Lennon VA, and McKeon A
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Biomarkers blood, Biomarkers cerebrospinal fluid, Child, Encephalomyelitis blood, Encephalomyelitis cerebrospinal fluid, Encephalomyelitis diagnosis, Female, HEK293 Cells, Humans, Immunoglobulin G blood, Immunoglobulin G cerebrospinal fluid, Male, Meningoencephalitis blood, Meningoencephalitis cerebrospinal fluid, Meningoencephalitis diagnosis, Middle Aged, Prospective Studies, Young Adult, Astrocytes metabolism, Astrocytes pathology, Autoimmunity physiology, Glial Fibrillary Acidic Protein blood, Glial Fibrillary Acidic Protein cerebrospinal fluid
- Abstract
In this prospective evaluation of serum and CSF samples, all but two CSF GFAPα-IgG positive patients had autoimmune meningoencephalomyelitis while serum GFAPα-IgG positivity alone was less specific. Phenotypes were diverse among patients that were serum positive only. Adult and pediatric clinical presentations were similar. Most patients were immunotherapy responsive. Co-existing NMDA-R-IgG and cancer were associated with lack of response to first-line immunotherapy. Among patients with follow-up information, 18% had relapses. This study demonstrates CSF GFAPα-IgG is a specific autoimmune meningoencephalomyelitis biomarker, with favorable corticosteroid response. Lack of response should prompt evaluation for co-existing NMDA-R-IgG or malignancy., (Copyright © 2018 Elsevier B.V. All rights reserved.)
- Published
- 2018
- Full Text
- View/download PDF
7. New insights into neuropathology and pathogenesis of autoimmune glial fibrillary acidic protein meningoencephalomyelitis
- Author
-
Guo, Yong, Endmayr, Verena, Zekeridou, Anastasia, McKeon, Andrew, Leypoldt, Frank, Hess, Katharina, Kalinowska-Lyszczarz, Alicja, Klang, Andrea, Pakozdy, Akos, Höftberger, Elisabeth, Hametner, Simon, Haider, Carmen, De Simoni, Désirée, Peters, Sönke, Gelpi, Ellen, Röcken, Christoph, Oberndorfer, Stefan, Lassmann, Hans, Lucchinetti, Claudia F., and Höftberger, Romana
- Published
- 2024
- Full Text
- View/download PDF
8. High-resolution epitope mapping of anti-Hu and anti-Yo autoimmunity by programmable phage display
- Author
-
O’Donovan, Brian, Mandel-Brehm, Caleigh, Vazquez, Sara E, Liu, Jamin, Parent, Audrey V, Anderson, Mark S, Kassimatis, Travis, Zekeridou, Anastasia, Hauser, Stephen L, Pittock, Sean J, Chow, Eric, Wilson, Michael R, and DeRisi, Joseph L
- Subjects
Biomedical and Clinical Sciences ,Immunology ,Genetics ,Neurosciences ,Biotechnology ,2.1 Biological and endogenous factors ,Aetiology ,phage display ,autoimmunity ,anti-Hu ,anti-Yo ,paraneoplastic ,Clinical sciences ,Biological psychology - Abstract
Paraneoplastic neurological disorders are immune-mediated diseases understood to manifest as part of a misdirected anti-tumor immune response. Paraneoplastic neurological disorder-associated autoantibodies can assist with diagnosis and enhance our understanding of tumor-associated immune processes. We designed a comprehensive library of 49-amino-acid overlapping peptides spanning the entire human proteome, including all splicing isoforms and computationally predicted coding regions. Using this library, we optimized a phage immunoprecipitation and sequencing protocol with multiple rounds of enrichment to create high-resolution epitope profiles in serum and cerebrospinal fluid (CSF) samples from patients suffering from two common paraneoplastic neurological disorders, the anti-Yo (n = 36 patients) and anti-Hu (n = 44 patients) syndromes. All (100%) anti-Yo patient samples yielded enrichment of peptides from the canonical anti-Yo (CDR2 and CDR2L) antigens, while 38% of anti-Hu patients enriched peptides deriving from the nELAVL (neuronal embryonic lethal abnormal vision like) family of proteins, the anti-Hu autoantigenic target. Among the anti-Hu patient samples that were positive for nELAVL, we noted a restricted region of immunoreactivity. To achieve single amino acid resolution, we designed a novel deep mutational scanning phage library encoding all possible single-point mutants targeting the reactive nELAVL region. This analysis revealed a distinct preference for the degenerate motif, RLDxLL, shared by ELAVL2, 3 and 4. Lastly, phage immunoprecipitation sequencing identified several known autoantigens in these same patient samples, including peptides deriving from the cancer-associated antigens ZIC and SOX families of transcription factors. Overall, this optimized phage immunoprecipitation sequencing library and protocol yielded the high-resolution epitope mapping of the autoantigens targeted in anti-Yo and anti-Hu encephalitis patients to date. The results presented here further demonstrate the utility and high-resolution capability of phage immunoprecipitation sequencing for both basic science and clinical applications and for better understanding the antigenic targets and triggers of paraneoplastic neurological disorders.
- Published
- 2020
9. High-resolution epitope mapping of anti-Hu and anti-Yo autoimmunity by programmable phage display.
- Author
-
O'Donovan, Brian, Mandel-Brehm, Caleigh, Vazquez, Sara E, Liu, Jamin, Parent, Audrey V, Anderson, Mark S, Kassimatis, Travis, Zekeridou, Anastasia, Hauser, Stephen L, Pittock, Sean J, Chow, Eric, Wilson, Michael R, and DeRisi, Joseph L
- Subjects
anti-Hu ,anti-Yo ,autoimmunity ,paraneoplastic ,phage display - Abstract
Paraneoplastic neurological disorders are immune-mediated diseases understood to manifest as part of a misdirected anti-tumor immune response. Paraneoplastic neurological disorder-associated autoantibodies can assist with diagnosis and enhance our understanding of tumor-associated immune processes. We designed a comprehensive library of 49-amino-acid overlapping peptides spanning the entire human proteome, including all splicing isoforms and computationally predicted coding regions. Using this library, we optimized a phage immunoprecipitation and sequencing protocol with multiple rounds of enrichment to create high-resolution epitope profiles in serum and cerebrospinal fluid (CSF) samples from patients suffering from two common paraneoplastic neurological disorders, the anti-Yo (n = 36 patients) and anti-Hu (n = 44 patients) syndromes. All (100%) anti-Yo patient samples yielded enrichment of peptides from the canonical anti-Yo (CDR2 and CDR2L) antigens, while 38% of anti-Hu patients enriched peptides deriving from the nELAVL (neuronal embryonic lethal abnormal vision like) family of proteins, the anti-Hu autoantigenic target. Among the anti-Hu patient samples that were positive for nELAVL, we noted a restricted region of immunoreactivity. To achieve single amino acid resolution, we designed a novel deep mutational scanning phage library encoding all possible single-point mutants targeting the reactive nELAVL region. This analysis revealed a distinct preference for the degenerate motif, RLDxLL, shared by ELAVL2, 3 and 4. Lastly, phage immunoprecipitation sequencing identified several known autoantigens in these same patient samples, including peptides deriving from the cancer-associated antigens ZIC and SOX families of transcription factors. Overall, this optimized phage immunoprecipitation sequencing library and protocol yielded the high-resolution epitope mapping of the autoantigens targeted in anti-Yo and anti-Hu encephalitis patients to date. The results presented here further demonstrate the utility and high-resolution capability of phage immunoprecipitation sequencing for both basic science and clinical applications and for better understanding the antigenic targets and triggers of paraneoplastic neurological disorders.
- Published
- 2020
10. Neurological autoimmunity in patients with non‐pulmonary neuroendocrine neoplasms: clinical manifestations and neural autoantibody profiles.
- Author
-
Mangioris, Georgios, Halfdanarson, Thorvardur R., Lennon, Vanda A., Chang, Bryce K., Dubey, Divyanshu, Dyck, P. James B., Flanagan, Eoin P., McKeon, Andrew, Mills, John R., Pittock, Sean J., and Zekeridou, Anastasia
- Subjects
NEUROENDOCRINE tumors ,SYMPTOMS ,AUTOIMMUNE diseases ,AUTOANTIBODIES ,NEUROMUSCULAR diseases ,AUTOIMMUNITY - Abstract
Background and purpose: Paraneoplastic neurological autoimmunity is well described with small‐cell lung cancer, but information is limited for other neuroendocrine neoplasms (NENs). Methods: Adult patients with histopathologically confirmed non‐pulmonary NENs, neurological autoimmunity within 5 years of NEN diagnosis, and neural antibody testing performed at the Mayo Clinic Neuroimmunology Laboratory (January 2008 to March 2023) were retrospectively identified. Control sera were available from patients with NENs without neurological autoimmunity (116). Results: Thirty‐four patients were identified (median age 68 years, range 31–87). The most common primary tumor sites were pancreas (nine), skin (Merkel cell, eight), small bowel/duodenum (seven), and unknown (seven). Five patients received immune checkpoint inhibitor (ICI) therapy before symptom onset; symptoms preceded cancer diagnosis in 62.1% of non‐ICI‐treated patients. The most frequent neurological phenotypes (non‐ICI‐treated) were movement disorders (12; cerebellar ataxia in 10), dysautonomia (six), peripheral neuropathy (eight), encephalitis (four), and neuromuscular junction disorders (four). Neural antibodies were detected in 55.9% of patients studied (most common specificities: P/Q‐type voltage‐gated calcium channel [seven], muscle‐type acetylcholine receptor [three], anti‐neuronal nuclear antibody type 1 [three], and neuronal intermediate filaments [two]), but in only 6.9% of controls. Amongst patients receiving cancer or immunosuppressive therapy, 51.6% had partial or complete recovery. Outcomes were unfavorable in 48.3% (non‐ICI‐treated) and neural autoantibody positivity was associated with poor neurological outcome. Discussion: Neurological autoimmunity associated with non‐pulmonary NENs is often multifocal and can be treatment responsive, underscoring the importance of rapid recognition and early treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
11. CDR2 and CDR2L line blot performance in PCA-1/anti-Yo paraneoplastic autoimmunity.
- Author
-
Vorasoot, Nisa, Scharf, Madeleine, Miske, Ramona, Thakolwiboon, Smathorn, Dubey, Divyanshu, Mills, John R., Pittock, Sean J., Zekeridou, Anastasia, Ott, Anthonina, and McKeon, Andrew
- Subjects
CEREBELLUM degeneration ,IMMUNOGLOBULIN G ,AUTOIMMUNITY ,CEREBROSPINAL fluid ,MEDIAN (Mathematics) - Abstract
Background: Purkinje cytoplasmic autoantibody type 1 (PCA-1)/anti-Yo autoimmunity is a common high-risk paraneoplastic neurological disorder, traditionally attributed antigenically to cerebellar degeneration--related protein 2 (CDR2), predominantly affecting women with gynecologic or breast adenocarcinoma. Single-modality CDR2 testing may produce false-positive results. We assessed the performance characteristics of the more recently purported major PCA-1/Yo antigen, CDR2-like (CDR2L), side by side with CDR2, in a line blot format. Methods: CDR2 and CDR2L were tested in six specimen groups (serum and cerebrospinal fluid (CSF)). Group 1, PCA-1/Yo mouse brain indirect immunofluorescence assay (IFA) positives; Group 2, PCA-1/Yo IFA mimics; Group 3, suspected CDR2 line blot false positives; Group 4, consecutive patient samples tested for neural antibodies over 1 year; Group 5, healthy subject serums; and Group 6, polyclonal (non-specific) immunoglobulin G (IgG)-positive serums. Results: Group 1: Of 64 samples tested, all but two were CDR2 positive (both CSF samples) and all were CDR2L positive. In individual patients, CDR2L values were always higher than CDR2. The two "CDR2L-only" positives were CSF samples with low titer PCA-1/Yo by IFA with serum negativity but with typical clinical phenotype. Group 2: All 51 PCA-1/Yo mimics were CDR2/CDR2L negative. Group 3: Nine samples [six of 1289 (0.47%) serums and three of 700 CSF samples (0.43%) were PCA-1/Yo IFA negative/CDR2 positive; two of the six available (serums from the same patient) were also CDR2L positive; the other four CDR2L negative had low CDR2 values (17--22). Group 4: Twenty-two patients had unexpected CDR2 or CDR2L positivity; none had tissue IFA positivity. Eleven of the 2,132 serum (0.5%) and three of the 677 CSF (0.4%) samples were CDR2 positive; median value was 19 (range, 11--48). Seven of the 2,132 serum(0.3%) and three of the 677 CSF (0.4%) samples were CDR2L positive; median value was 18 (range, 11--96). Group 5: All 151 healthy serumsamples were negative. Group 6: One of the 46 polyclonal serum samples was CDR2L positive. Optimum overall performance was accomplished by requiring both CDR2 and CDR2L positivity in serum (sensitivity, 100%; and specificity, 99.9%) and positivity for CDR2L in CSF (sensitivity, 100%; and specificity, 99.6%). Conclusion: CDR2L provides additional PCA-1/anti-Yo sensitivity in CSF, and dual positivity with CDR2 provides additional specificity assurance in serum. Combining antigen-specific and tissue-based assays optimizes PCA-1/anti-Yo testing. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
12. Tenascin‐R Autoimmunity: Isolated Tremor Reversed with Immunotherapy.
- Author
-
Yang, Binxia, Brown, Andrew, McKeon, Andrew, Ahlskog, J. Eric, Tipton, Philip, Guo, Yong, Lucchinetti, Claudia, Pittock, Sean J., and Zekeridou, Anastasia
- Subjects
MOVEMENT disorders ,TREMOR ,CEREBROSPINAL fluid ,FOLLICULAR lymphoma ,AUTOIMMUNITY ,IMMUNOTHERAPY - Abstract
Autoimmune movement disorders are increasingly recognized, but isolated tremor is extremely rare. We describe a 70‐year‐old male with rapidly progressive, severe postural and intention tremor and weight loss. His cerebrospinal fluid was inflammatory and harbored a neural tissue‐restricted antibody. The autoantigen was identified by immunoprecipitation and mass spectrometry and confirmed by antigen‐specific assays to be specific for tenascin‐R. He was investigated for cancer and diagnosed with follicular lymphoma that expressed tenascin‐R suggesting a paraneoplastic origin; cancer treatment and immunotherapy led to complete recovery. With this individualized patient approach and antibody discovery, we expand the spectrum of antibodies accompanying autoimmune hyperkinetic movement disorders. ANN NEUROL 2023;94:502–507 [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
13. Immune checkpoint inhibitor‐associated central nervous system autoimmunity.
- Author
-
Valencia‐Sanchez, Cristina, Sechi, Elia, Dubey, Divyanshu, Flanagan, Eoin P., McKeon, Andrew, Pittock, Sean J., and Zekeridou, Anastasia
- Subjects
IMMUNE checkpoint proteins ,CENTRAL nervous system ,AUTOIMMUNE diseases ,SMALL cell lung cancer ,PARANEOPLASTIC syndromes ,IPILIMUMAB ,PERIPHERAL nervous system ,AUTOIMMUNITY - Abstract
Background and purpose: Outcome and rechallenge data on central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICIs) are limited. We aim to describe a large series of patients with ICI‐triggered CNS autoimmunity, and to compare these patients with spontaneous paraneoplastic syndromes (PNS). Methods: We retrospectively reviewed Mayo Clinic patients with ICI‐triggered CNS autoimmunity (February 2015–June 2021). Clinical characteristics were compared to spontaneous PNS patients (with antineuronal nuclear antibody [ANNA]‐1 or anti‐Hu neurological autoimmunity, and/or neuroendocrine tumors [NET]) evaluated within the same period. Results: Thirty‐one patients were included (55% female, median age = 63 years, range = 39–76). Median time from ICI initiation was 3.65 months (range = 0.8–44.5). The most common associated malignancies were melanoma and small cell lung cancer. CNS manifestations included encephalitis (n = 16), meningoencephalitis (n = 8), cerebellar ataxia (n = 4), demyelinating syndrome (n = 2), and myelopathy (n = 1). Magnetic resonance imaging was abnormal in 62%. Cerebrospinal fluid was inflammatory in 70%. Neural autoantibodies were identified in 47%, more frequently in patients with NET (p = 0.046). ICI was discontinued in 97%; 90% received immunosuppressive treatment. After median 6.8 months follow‐up (range = 0.7–46), 39% had unfavorable outcomes (grade ≥ 3). This was associated with higher severity degree at onset, shorter period from ICI to neurological symptom onset, and encephalitis. Four patients were rechallenged with ICI, and one relapsed. Patients with NET and with ANNA‐1 ICI‐triggered CNS autoimmunity had associated peripheral nervous system manifestations more frequently than their spontaneous counterparts (p = 0.007 and p = 0.028, respectively). Conclusions: One third of ICI‐related CNS autoimmunity patients have unfavorable outcomes. Relapses may occur after ICI rechallenge. Neural autoantibodies are often present, more commonly in patients with NET. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
14. Case Report: Innate Immune System Challenge Unleashes Paraneoplastic Neurological Autoimmunity.
- Author
-
Zhu, Mingqin, Ma, Yuetao, Zekeridou, Anastasia, and Lennon, Vanda A.
- Subjects
IMMUNE system ,ALTERNATIVE treatment for cancer ,PERIPHERAL nervous system ,NERVE tissue proteins ,AUTOIMMUNITY ,PARANEOPLASTIC syndromes ,BCG vaccines ,APOPTIN - Abstract
Paraneoplastic autoimmune neurological disorders reflect tumor-initiated immune responses against onconeural antigens. Symptoms and signs can affect the central and/or peripheral nervous systems, neuromuscular junction or muscle, and typically evolve subacutely before an underlying neoplasm is discovered. We describe four patients whose neurological symptoms were precipitated by potent innate immune system challenges: bladder instillation of BCG, tick bite and an "alternative cancer therapy" with bacterial extracts and TNF-α. We hypothesize that a tumor-initiated autoimmune response (evidenced by autoantibody profiles), pre-dating the immune system challenge, was unmasked or amplified in these patients by cytokines released systemically from innate immune cells activated by microbial pathogen-associated molecular patterns (PAMPs). The resultant upregulation of cognate onconeural peptides as MHC1 protein complexes on neural cell surfaces would render those cells susceptible to killing by CD8+ T cells, thus precipitating the patient's neurological symptoms. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
15. Synaptic autoimmunity: new insights into LGI1 antibody-mediated neuronal dysfunction.
- Author
-
Zekeridou, Anastasia and Pittock, Sean J
- Subjects
FRONTOTEMPORAL lobar degeneration ,NERVE tissue proteins ,ANTI-NMDA receptor encephalitis ,CEREBROSPINAL fluid ,AUTOIMMUNITY ,GLUTAMATE transporters ,SYNAPTOPHYSIN ,ANTIBODY-dependent cell cytotoxicity ,AUTOANTIBODIES ,IMMUNITY ,NEURAL transmission ,NEURONS ,SIGNAL peptides - Published
- 2020
- Full Text
- View/download PDF
16. Pre-existing antiacetylcholine receptor autoantibodies and B cell lymphopaenia are associated with the development of myositis in patients with thymoma treated with avelumab, an immune checkpoint inhibitor targeting programmed death-ligand 1.
- Author
-
Mammen, Andrew L., Rajan, Arun, Pak, Katherine, Lehky, Tanya, Casciola-Rosen, Livia, Donahue, Renee N., Lepone, Lauren M., Zekeridou, Anastasia, Pittock, Sean J., Hassan, Raffit, Schlom, Jeffrey, and Gulley, James L.
- Published
- 2019
- Full Text
- View/download PDF
17. Papillitis associated with IgLON5 autoimmunity: A novel clinical phenotype.
- Author
-
Li, Xiaoyang, Chen, John J., Hur, Minjun, Paton, Gillian R., McKeon, Andrew, and Zekeridou, Anastasia
- Subjects
- *
OPTIC disc edema , *OPTIC neuritis , *AUTOIMMUNITY , *MOVEMENT disorders , *PHENOTYPES - Abstract
To describe papillitis as a clinical phenotype of IgLON5 autoimmunity. We retrospectively reviewed patients with IgLON5 autoimmunity who had optic neuropathy, optic neuritis, or optic disc edema. Sera from patients with recurrent papillitis were tested for IgLON5 antibodies. We found two elderly males presenting with papillitis in the presence of IgLON5 antibodies. CSF pleocytosis was present and partial vision improvement occurred in one patient despite immunotherapy. Sera from 18 patients with recurrent papillitis were negative for IgLON5 antibodies. Papillitis could be a manifestation of IgLON5 disease, with or without accompanying cognitive, sleep, and movement disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
18. AMPAR autoimmunity: Neurological and oncological accompaniments and co-existing neural autoantibodies.
- Author
-
McCombe, Jennifer A., Zivelonghi, Cecilia, Vorasoot, Nisa, Majed, Masoud, Flanagan, Eoin P., Dubey, Divyanshu, Pittock, Sean J., McKeon, Andrew, and Zekeridou, Anastasia
- Subjects
- *
AUTOIMMUNE diseases , *AUTOANTIBODIES , *ANTI-NMDA receptor encephalitis , *SYMPTOMS , *AUTOIMMUNITY , *PROPIONIC acid - Abstract
α -amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) encephalitis is rare but treatable. We reviewed the clinical and autoantibody profiles of 52 AMPAR-IgG-positive patients (median age 48 years [range 12–81]; 38 female) identified at the Mayo Clinic neuroimmunology laboratory. Main presentation was encephalitis; symptoms other than encephalitis associated with co-existing antibodies (p = 0.004). A tumor was found in 33/44; mostly thymoma. Most patients had partial (14/29) or complete (11/29) immunotherapy response. Thirty-one patients had at least one co-existing antibody that predicted thymoma in paraneoplastic patients (p = 0.008). In conclusion, in AMPAR encephalitis co-existing antibodies predict clinical presentation other than encephalitis and thymoma. [Display omitted] • AMPAR-IgG-positive patients present with immunotherapy-responsive encephalitis. • 75% have an underlying malignancy making AMPAR-IgG a "high-risk" antibody. • Co-existing neural antibodies predict clinical presentation other than encephalitis. • Co-existing neural antibodies predict tumor association in paraneoplastic cases. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.