TY - JOUR
T1 - Autoimmune/Paraneoplastic Encephalitis Antibody Biomarkers
T2 - Frequency, Age, and Sex Associations
AU - Kunchok, Amy
AU - McKeon, Andrew
AU - Zekeridou, Anastasia
AU - Flanagan, Eoin P.
AU - Dubey, Divyanshu
AU - Lennon, Vanda A.
AU - Klein, Christopher Jon
AU - Mills, John R.
AU - Pittock, Sean J.
N1 - Funding Information:
Potential Competing Interests: Amy Kunchok has received research support from Biogen in a previous employment. Andrew McKeon has received research funding from Alexion, Grifols, and Viela Bio/MedImmune and has patents pending for IgGs as biomarkers of autoimmune neurologic disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B). Anastasia Zekeridou has a patent pending for PDE10A-IgG as a biomarker of autoimmune neurologic disorders. Eoin P. Flanagan is a site principal investigator in a randomized placebo-controlled clinical trial of inebilizumab (a CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune/Viela Bio. He receives no personal compensation and receives reimbursement just for the research activities related to the trial. Divyanshu Dubey has a patent pending for Kelch-like protein 11 as a marker of neurologic autoimmunity and has received research support from Grifols, Center for Clinical and Translational Science. Dr Dubey has consulted for UCB and Astellas. He has participated in UCB Advisory Board Meeting in Lyon, France, on September 23, 2019. All compensation for consulting activities is paid directly to Mayo Clinic. Dr Dubey has been a speaker at American Academy of Neurology Annual conference. All compensation for speaking activities is paid directly to Mayo Clinic. Vanda Lennon shares in royalties from RSR/Kronus Inc derived from a Mayo Clinic patent regarding diagnostic testing for AQP4 autoantibodies and has patents pending for IgGs as biomarkers of autoimmune neurologic disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B) and for ?Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive.? Christopher Klein is on the therapeutic CMTA advisory board. He has received teaching honorarium from Akcea pharmaceuticals for lectures on hereditary TTR amyloidosis and Fabry disease. He has consulted for Pfizer regarding tafamidus (all compensation for consulting activities is paid directly to Mayo Clinic). He has participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. John R. Mills holds patents on the use of mass spectrometry to measure monoclonal immunoglobulins and receives royalties related to these patents from The Binding Site. Sean J. Pittock reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals, Inc; grants from Grifols, Autoimmune Encephalitis Alliance; grants, personal fees, nonfinancial support, and other from Viela Bio/MedImmune, Inc. Dr Pittock has a patent #9,891,219 (Application#12-573942) ?Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive.? Dr Pittock also has patents pending for IgGs as biomarkers of autoimmune neurologic disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B).
Funding Information:
Potential Competing Interests: Amy Kunchok has received research support from Biogen in a previous employment. Andrew McKeon has received research funding from Alexion , Grifols , and Viela Bio / MedImmune and has patents pending for IgGs as biomarkers of autoimmune neurologic disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B). Anastasia Zekeridou has a patent pending for PDE10A-IgG as a biomarker of autoimmune neurologic disorders. Eoin P. Flanagan is a site principal investigator in a randomized placebo-controlled clinical trial of inebilizumab (a CD19 inhibitor) in neuromyelitis optica spectrum disorders funded by MedImmune / Viela Bio . He receives no personal compensation and receives reimbursement just for the research activities related to the trial. Divyanshu Dubey has a patent pending for Kelch-like protein 11 as a marker of neurologic autoimmunity and has received research support from Grifols , Center for Clinical and Translational Science . Dr Dubey has consulted for UCB and Astellas. He has participated in UCB Advisory Board Meeting in Lyon, France, on September 23, 2019. All compensation for consulting activities is paid directly to Mayo Clinic. Dr Dubey has been a speaker at American Academy of Neurology Annual conference. All compensation for speaking activities is paid directly to Mayo Clinic. Vanda Lennon shares in royalties from RSR/Kronus Inc derived from a Mayo Clinic patent regarding diagnostic testing for AQP4 autoantibodies and has patents pending for IgGs as biomarkers of autoimmune neurologic disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B) and for “Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive.” Christopher Klein is on the therapeutic CMTA advisory board. He has received teaching honorarium from Akcea pharmaceuticals for lectures on hereditary TTR amyloidosis and Fabry disease. He has consulted for Pfizer regarding tafamidus (all compensation for consulting activities is paid directly to Mayo Clinic). He has participated in the clinical trials for inotersen and patisiran but received no personal compensation for his participation. John R. Mills holds patents on the use of mass spectrometry to measure monoclonal immunoglobulins and receives royalties related to these patents from The Binding Site. Sean J. Pittock reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals , Inc; grants from Grifols , Autoimmune Encephalitis Alliance ; grants, personal fees, nonfinancial support, and other from Viela Bio / MedImmune , Inc. Dr Pittock has a patent #9,891,219 (Application#12-573942) “Methods for Treating Neuromyelitis Optica (NMO) by Administration of Eculizumab to an individual that is Aquaporin-4 (AQP4)-IgG Autoantibody positive.” Dr Pittock also has patents pending for IgGs as biomarkers of autoimmune neurologic disorders (septin-5, Kelch-like protein 11, GFAP, PDE10A, and MAP1B).
Publisher Copyright:
© 2021 Mayo Foundation for Medical Education and Research
PY - 2021
Y1 - 2021
N2 - Objective: To determine the frequency of detection and the age and sex associations of autoimmune/paraneoplastic encephalitis antibody biomarkers (AE-Abs). Methods: There were 42,032 patients tested in the Mayo Clinic Neuroimmunology Laboratory between January 2018 and December 2019 for AE-Abs in serum or cerebrospinal fluid (CSF), including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, CASPR2-IgG, LGI1-IgG, GAD65-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1/2/Tr-IgGs, ANNA1/2/3-IgGs, GFAP-IgG, mGluR1-IgG, DPPX-IgG, and MOG-IgG1. Results were examined to determine frequency of antibody positivity. Age and sex associations were examined by multivariable logistic regression. Results: Adult serum analysis (22,472 patients; 56% female) revealed that 814 (3.6%) were positive: NMDA-R-IgG (24.6%) > GAD65-IgG (21.5%) > LGI1-IgG (20.5%) > others. Of children (5649; 50% female), 251 (4.4%) were positive: NMDA-R-IgG (53.1%) > MOG-IgG1 (32%) > GAD65-IgG (7.1%) > others. Adult CSF analysis (18,745 patients; 54% female) revealed that 796 (4.2%) were positive: NMDA-R-IgG (39.7%) > GAD65-IgG (28.5%) > LGI1-IgG (11.4%) > others. Of children (5136; 50% female), 282 (5.5%) were positive: NMDA-R-IgG (88.1%) > GAD65-IgG (8.7%) > others. Age younger than 20 years was associated with NMDA-R-IgG and MOG-IgG1 (odds ratio [OR], 8.11 and 7.84, respectively; P<.001). Age older than 65 years was associated with GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, and ANNA1-IgG (OR, 7.33, 14.98, 3.67, and 14.53; P<.001). Women accounted for 60% of NMDA-R-IgG (CSF) and 78% of GAD65-IgG (CSF and serum) cohorts (OR, 1.32 [P=.002] and 2.23 [P<.001], respectively). Men accounted for 62% of the LGI1-IgG cohort (OR, 1.87; P<.001). Age and sex interacted for NMDA-R-IgG, particularly in female patients younger than 20 years (OR, 7.72; P<.001). Conclusion: The most frequent AE-Abs detected were NMDA-R-IgG, GAD65-IgG, LGI1-IgG, and MOG-IgG1. Age and sex associations may suggest paraneoplastic, or aging influences on neurologic autoimmunity.
AB - Objective: To determine the frequency of detection and the age and sex associations of autoimmune/paraneoplastic encephalitis antibody biomarkers (AE-Abs). Methods: There were 42,032 patients tested in the Mayo Clinic Neuroimmunology Laboratory between January 2018 and December 2019 for AE-Abs in serum or cerebrospinal fluid (CSF), including NMDA-R-IgG, AMPA-R-IgG, GABAB-R-IgG, CASPR2-IgG, LGI1-IgG, GAD65-IgG, CRMP5-IgG, amphiphysin-IgG, PCA1/2/Tr-IgGs, ANNA1/2/3-IgGs, GFAP-IgG, mGluR1-IgG, DPPX-IgG, and MOG-IgG1. Results were examined to determine frequency of antibody positivity. Age and sex associations were examined by multivariable logistic regression. Results: Adult serum analysis (22,472 patients; 56% female) revealed that 814 (3.6%) were positive: NMDA-R-IgG (24.6%) > GAD65-IgG (21.5%) > LGI1-IgG (20.5%) > others. Of children (5649; 50% female), 251 (4.4%) were positive: NMDA-R-IgG (53.1%) > MOG-IgG1 (32%) > GAD65-IgG (7.1%) > others. Adult CSF analysis (18,745 patients; 54% female) revealed that 796 (4.2%) were positive: NMDA-R-IgG (39.7%) > GAD65-IgG (28.5%) > LGI1-IgG (11.4%) > others. Of children (5136; 50% female), 282 (5.5%) were positive: NMDA-R-IgG (88.1%) > GAD65-IgG (8.7%) > others. Age younger than 20 years was associated with NMDA-R-IgG and MOG-IgG1 (odds ratio [OR], 8.11 and 7.84, respectively; P<.001). Age older than 65 years was associated with GABAB-R-IgG, LGI1-IgG, CASPR2-IgG, and ANNA1-IgG (OR, 7.33, 14.98, 3.67, and 14.53; P<.001). Women accounted for 60% of NMDA-R-IgG (CSF) and 78% of GAD65-IgG (CSF and serum) cohorts (OR, 1.32 [P=.002] and 2.23 [P<.001], respectively). Men accounted for 62% of the LGI1-IgG cohort (OR, 1.87; P<.001). Age and sex interacted for NMDA-R-IgG, particularly in female patients younger than 20 years (OR, 7.72; P<.001). Conclusion: The most frequent AE-Abs detected were NMDA-R-IgG, GAD65-IgG, LGI1-IgG, and MOG-IgG1. Age and sex associations may suggest paraneoplastic, or aging influences on neurologic autoimmunity.
UR - http://www.scopus.com/inward/record.url?scp=85121721923&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85121721923&partnerID=8YFLogxK
U2 - 10.1016/j.mayocp.2021.07.023
DO - 10.1016/j.mayocp.2021.07.023
M3 - Article
AN - SCOPUS:85121721923
JO - Mayo Clinic Proceedings
JF - Mayo Clinic Proceedings
SN - 0025-6196
ER -