Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients

Eoin P. Flanagan; Shannon R. Hinson; Vanda A. Lennon; Boyan Fang; Allen J. Aksamit; P. Pearse Morris; Eati Basal; Josephe A. Honorat; Nora B. Alfugham; Jenny J. Linnoila; Brian G. Weinshenker; Sean J. Pittock; Andrew McKeon

doi:10.1002/ana.24881

Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients

Eoin P. Flanagan, Shannon R. Hinson, Vanda A. Lennon, Boyan Fang, Allen J. Aksamit, P. Pearse Morris, Eati Basal, Josephe A. Honorat, Nora B. Alfugham, Jenny J. Linnoila, Brian G. Weinshenker, Sean J. Pittock, Andrew McKeon

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141 Scopus citations

Abstract

Objective: A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described. Methods: The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell-based (n = 323) assays. Results: Median symptom onset age was 44 years (range = 8–103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP-IgG positivity was encountered in serum controls by tissue-based assay (0.5%) or cell-based assay (1.5%), and in CSF controls by cell-based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N-methyl-D-aspartate receptor–IgG and aquaporin-4–IgG coexisted (71%). Six patients with prolonged follow-up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. Interpretation: GFAPα-IgG, when detected in CSF, is highly specific for an immunotherapy-responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298–309.

Original language	English (US)
Pages (from-to)	298-309
Number of pages	12
Journal	Annals of neurology
Volume	81
Issue number	2
DOIs	https://doi.org/10.1002/ana.24881
State	Published - Feb 1 2017

ASJC Scopus subject areas

Neurology
Clinical Neurology

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10.1002/ana.24881

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Flanagan, E. P., Hinson, S. R., Lennon, V. A., Fang, B., Aksamit, A. J., Morris, P. P., Basal, E., Honorat, J. A., Alfugham, N. B., Linnoila, J. J., Weinshenker, B. G., Pittock, S. J., & McKeon, A. (2017). Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients. Annals of neurology, 81(2), 298-309. https://doi.org/10.1002/ana.24881

Flanagan, EP, Hinson, SR, Lennon, VA, Fang, B, Aksamit, AJ, Morris, PP, Basal, E, Honorat, JA, Alfugham, NB, Linnoila, JJ, Weinshenker, BG, Pittock, SJ & McKeon, A 2017, 'Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients', Annals of neurology, vol. 81, no. 2, pp. 298-309. https://doi.org/10.1002/ana.24881

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title = "Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients",

abstract = "Objective: A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described. Methods: The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell-based (n = 323) assays. Results: Median symptom onset age was 44 years (range = 8–103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP-IgG positivity was encountered in serum controls by tissue-based assay (0.5%) or cell-based assay (1.5%), and in CSF controls by cell-based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N-methyl-D-aspartate receptor–IgG and aquaporin-4–IgG coexisted (71%). Six patients with prolonged follow-up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. Interpretation: GFAPα-IgG, when detected in CSF, is highly specific for an immunotherapy-responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298–309.",

author = "Flanagan, {Eoin P.} and Hinson, {Shannon R.} and Lennon, {Vanda A.} and Boyan Fang and Aksamit, {Allen J.} and Morris, {P. Pearse} and Eati Basal and Honorat, {Josephe A.} and Alfugham, {Nora B.} and Linnoila, {Jenny J.} and Weinshenker, {Brian G.} and Pittock, {Sean J.} and Andrew McKeon",

note = "Publisher Copyright: {\textcopyright} 2017 American Neurological Association",

year = "2017",

month = feb,

day = "1",

doi = "10.1002/ana.24881",

language = "English (US)",

volume = "81",

pages = "298--309",

journal = "Annals of neurology",

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T1 - Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy

T2 - Analysis of 102 patients

AU - Flanagan, Eoin P.

AU - Hinson, Shannon R.

AU - Lennon, Vanda A.

AU - Fang, Boyan

AU - Aksamit, Allen J.

AU - Morris, P. Pearse

AU - Basal, Eati

AU - Honorat, Josephe A.

AU - Alfugham, Nora B.

AU - Linnoila, Jenny J.

AU - Weinshenker, Brian G.

AU - Pittock, Sean J.

AU - McKeon, Andrew

PY - 2017/2/1

Y1 - 2017/2/1

N2 - Objective: A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described. Methods: The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell-based (n = 323) assays. Results: Median symptom onset age was 44 years (range = 8–103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP-IgG positivity was encountered in serum controls by tissue-based assay (0.5%) or cell-based assay (1.5%), and in CSF controls by cell-based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N-methyl-D-aspartate receptor–IgG and aquaporin-4–IgG coexisted (71%). Six patients with prolonged follow-up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. Interpretation: GFAPα-IgG, when detected in CSF, is highly specific for an immunotherapy-responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298–309.

AB - Objective: A novel autoimmune central nervous system (CNS) disorder with glial fibrillary acidic protein (GFAP)-IgG as biomarker was recently characterized. Here, 102 patients with GFAP-IgG positivity are described. Methods: The 102 included patients had: (1) serum, cerebrospinal fluid (CSF), or both that yielded a characteristic astrocytic pattern of mouse tissue immunostaining; (2) confirmation of IgG reactive with specific GFAP isoforms (α, ɛ, or κ) by cell-based assays; and (3) clinical data available. Control specimens (n = 865) were evaluated by tissue (n = 542) and cell-based (n = 323) assays. Results: Median symptom onset age was 44 years (range = 8–103), and 54% were women. The predominant phenotype (83 patients; 81%) was inflammation of meninges, brain, spinal cord, or all 3 (meningoencephalomyelitis). Among patients, highest specificity for those phenotypes was observed for CSF testing (94%), and highest sensitivity was for the GFAPα isoform (100%). Rare GFAP-IgG positivity was encountered in serum controls by tissue-based assay (0.5%) or cell-based assay (1.5%), and in CSF controls by cell-based assay (0.9%). Among patients, striking perivascular radial enhancement was found on brain magnetic resonance imaging in 53%. Although cases frequently mimicked vasculitis, angiography was uniformly negative, and spinal imaging frequently demonstrated longitudinally extensive myelitic lesions. Diverse neoplasms encountered were found prospectively in 22%. Ovarian teratoma was most common and was predicted best when both N-methyl-D-aspartate receptor–IgG and aquaporin-4–IgG coexisted (71%). Six patients with prolonged follow-up had brisk corticosteroid response, but required additional immunosuppression to overcome steroid dependency. Interpretation: GFAPα-IgG, when detected in CSF, is highly specific for an immunotherapy-responsive autoimmune CNS disorder, sometimes with paraneoplastic cause. Ann Neurol 2017;81:298–309.

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Glial fibrillary acidic protein immunoglobulin G as biomarker of autoimmune astrocytopathy: Analysis of 102 patients

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