TY - JOUR
T1 - Clinical Utility of Striational Antibodies in Paraneoplastic and Myasthenia Gravis Paraneoplastic Panels
AU - Shelly, Shahar
AU - Mills, John R.
AU - Dubey, Divyanshu
AU - McKeon, Andrew
AU - Zekeridou, Anastasia
AU - Pittock, Sean J.
AU - Harper, C. Michel
AU - Naddaf, Elie
AU - Milone, Margherita
AU - Mandrekar, Jay
AU - Klein, Christopher J.
N1 - Funding Information:
Dr. Shelly and Dr. Mills report no disclosures. Dr. Dubey reports research support from Center of Multiple Sclerosis and Autoimmune Neurology and Grifols Pharmaceuticals and has consulted for UCB Pharmaceuticals. All compensation for consulting activities is paid directly to the Mayo Clinic. Dr. McKeon has a patent pending for MAP1B as a marker of neurologic autoimmunity and paraneoplastic disorders; consulted for Grifols, Medimmune, and Euroimmun without personal compensation; and received research support from Medimmune and Euroimmun. Dr. Zekeridou reports a patent for PDE10A-IgG as a biomarker of neurologic autoimmunity. Dr. Pittock reports grants, personal fees, and nonfinancial support from Alexion Pharmaceuticals, Inc.; grants from Grifols and Autoimmune Encephalitis Alliance; grants, personal fees, nonfinancial support, and other from Viela Bio and Astellas; personal consultation fees from UCB, Astellas, and Roche; and has patents 8,889,102 (application 12–678350; Neuromyelitis Optica Autoantibodies as a Marker for Neoplasia—issued), 9,891,219B2 (application 12–573942; Methods for Treating Neuromyelitis Optica by Administration of Eculizumab to an Individual That Is Aquaporin-4–IgG Autoantibody Positive—issued), and pending patents on GFAP-IgG, Septin-5-IgG, MAP1B-IgG, and KLHL11. Dr. Harper and Dr. Naddaf report no disclosures. Dr. Milone reports research funding from a Mayo Clinic benefactor (John Lawyer) and honorarium to serve as associate editor for Neurology Genetics. Dr. Mandrekar reports no disclosures. Dr. Klein reports he is on the therapeutic CMTA advisory board; has received teaching honorarium from Ackea Pharmaceuticals for lectures on hereditary TTR amyloidosis and Fabry disease; is a paid consultant to Pfizer regarding tafamidis but has received no personal compensation; and has participated in clinical trials for inotersen and patisiran but received no personal compensation for his participation. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
Copyright © 2021 American Academy of Neurolo
PY - 2021/6/15
Y1 - 2021/6/15
N2 - Objective To critically assess the clinical utility of striational antibodies (StrAbs) within paraneoplastic and myasthenia gravis (MG) serologic evaluations. Methods All Mayo Clinic patients tested for StrAbs from January 1, 2012, to December 31, 2018, utilizing Mayo's Unified Data Platform (UDP) were reviewed for neurologic diagnosis and cancer. Results A total of 38,502 unique paraneoplastic evaluations and 1,899 patients with MG were tested. In paraneoplastic evaluations, the StrAbs positivity rate was higher in cancer vs without cancer (5% [321/6,775] vs 4% [1,154/31,727]; p < 0.0001; odds ratio [OR] 1.35; confidence interval [CI] 1.19-1.53), but receiver operating characteristic (ROC) analysis indicated no diagnostic accuracy in cancer (area under the ROC curve [AUC] 0.505). No neurologic phenotype was significantly associated with StrAbs in the paraneoplastic group. Positivity was more common in all MG cancers compared to paraneoplastic cancers (p < 0.0001). In MG evaluations, the StrAbs positivity rate was higher in those with cancer vs without (46% [217/474] vs 26% [372/1,425]; p < 0.0001; OR 2.39, CI 1.9-2.96), with ROC analysis indicating poor diagnostic accuracy for thymic cancer (AUC 0.634, recommended cutoff = 1:60, sensitivity = 56%, specificity = 71%), with worse accuracy for extrathymic cancers (AUC 0.543). In paraneoplastic or MG evaluations, the value of antibody positivity did not improve cancer predictions. Paraneoplastic evaluated patients with positive StrAbs were more likely to obtain CT (p = 0.0001), with cancer found in 3% (12/468). Conclusion Despite a statistically significant association with cancer, an expansive review of performance in clinical service demonstrates that StrAbs are neither specific nor sensitive in predicting malignancy or neurologic phenotypes. CT imaging is overutilized with positive StrAbs results. Removal of StrAbs from paraneoplastic or MG evaluations will improve the diagnostic characteristics of the current MG test.
AB - Objective To critically assess the clinical utility of striational antibodies (StrAbs) within paraneoplastic and myasthenia gravis (MG) serologic evaluations. Methods All Mayo Clinic patients tested for StrAbs from January 1, 2012, to December 31, 2018, utilizing Mayo's Unified Data Platform (UDP) were reviewed for neurologic diagnosis and cancer. Results A total of 38,502 unique paraneoplastic evaluations and 1,899 patients with MG were tested. In paraneoplastic evaluations, the StrAbs positivity rate was higher in cancer vs without cancer (5% [321/6,775] vs 4% [1,154/31,727]; p < 0.0001; odds ratio [OR] 1.35; confidence interval [CI] 1.19-1.53), but receiver operating characteristic (ROC) analysis indicated no diagnostic accuracy in cancer (area under the ROC curve [AUC] 0.505). No neurologic phenotype was significantly associated with StrAbs in the paraneoplastic group. Positivity was more common in all MG cancers compared to paraneoplastic cancers (p < 0.0001). In MG evaluations, the StrAbs positivity rate was higher in those with cancer vs without (46% [217/474] vs 26% [372/1,425]; p < 0.0001; OR 2.39, CI 1.9-2.96), with ROC analysis indicating poor diagnostic accuracy for thymic cancer (AUC 0.634, recommended cutoff = 1:60, sensitivity = 56%, specificity = 71%), with worse accuracy for extrathymic cancers (AUC 0.543). In paraneoplastic or MG evaluations, the value of antibody positivity did not improve cancer predictions. Paraneoplastic evaluated patients with positive StrAbs were more likely to obtain CT (p = 0.0001), with cancer found in 3% (12/468). Conclusion Despite a statistically significant association with cancer, an expansive review of performance in clinical service demonstrates that StrAbs are neither specific nor sensitive in predicting malignancy or neurologic phenotypes. CT imaging is overutilized with positive StrAbs results. Removal of StrAbs from paraneoplastic or MG evaluations will improve the diagnostic characteristics of the current MG test.
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U2 - 10.1212/WNL.0000000000012050
DO - 10.1212/WNL.0000000000012050
M3 - Article
C2 - 33903199
AN - SCOPUS:85130593065
SN - 0028-3878
VL - 96
SP - E2966-E2976
JO - Neurology
JF - Neurology
IS - 24
ER -