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 J.
AU - Mills, John R.
AU - Pittock, Sean J.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2022/3
Y1 - 2022/3
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.
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U2 - 10.1016/j.mayocp.2021.07.023
DO - 10.1016/j.mayocp.2021.07.023
M3 - Article
C2 - 34955239
AN - SCOPUS:85121721923
SN - 0025-6196
VL - 97
SP - 547
EP - 559
JO - Mayo Clinic proceedings
JF - Mayo Clinic proceedings
IS - 3
ER -