PMID- 32938782
OWN - NLM
STAT- MEDLINE
DCOM- 20201216
LR  - 20201216
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Linking)
VI  - 95
IP  - 22
DP  - 2020 Dec 1
TI  - Improving accuracy of myasthenia gravis autoantibody testing by reflex algorithm.
PG  - e3002-e3011
LID - 10.1212/WNL.0000000000010910 [doi]
AB  - OBJECTIVE: To improve myasthenia gravis (MG) autoantibody testing. METHODS: MG 
      serologic tests with confirmatory or refuting clinical-electrodiagnostic (EDX) 
      testing and cancer evaluations were reviewed over 4 years (2012-2015). All 
      patients had acetylcholine receptor-binding (AChR-Bi), modulating (AChR-Mo), and 
      striational (STR) autoantibody testing, and negatives reflexed to muscle-specific 
      kinase (MuSK). Thymoma and cancer occurrences were correlated with STR and 
      reflexed glutamic acid decarboxylase 65 (GAD65), ganglionic acetylcholine 
      receptor (alpha3), collapsin response mediating protein-5, and voltage-gated 
      potassium channel complex autoantibodies. RESULTS: Of 433 samples tested, 133 
      (31%) met clinical-EDX criteria for MG. Best sensitivity (90%) occurred at 
      AChR-Bi >0.02 nmol/L, leaving 14 negative (6 ocular MG, 7 generalized MG, 1 MuSK 
      MG) with specificity 90% (31 false-positives). Using AChR-Mo antibodies (>20% 
      loss), specificity was better (92%, 24 false-positives), but sensitivity dropped 
      (85%). Specificity improved (95%) by testing AChR-Mo when AChR-Bi are positive, 
      resulting in 45% reduction of false-positives (31-17), maintaining AChR-Bi 90% 
      sensitivity. Cutoff values recommended by area under the curve analysis did not 
      outperform this approach. AChR-Bi and AChR-Mo values were significantly higher in 
      true-positives. CT evaluations in 121 MG samples revealed 16 thymomas. Historical 
      or subsequent cancers occurred in 22. STR and reflexed autoantibodies were not 
      more common in MG with thymoma or other cancers. Full-body CT (n = 34) was 
      performed in those with STR and reflex autoantibody positivity, but without 
      additional cancers found. CONCLUSION: Accuracy of MG serologic testing is 
      improved by reflexing AChR-Bi-positive cases to AChR-Mo. STR and other reflexed 
      cancer evaluation autoantibodies did not provide value beyond standard CT chest 
      imaging at the time of MG diagnosis. Diagnostic certainty is informed by AChR-Bi 
      and AChR-Mo with higher values increasing specificity.
CI  - (c) 2020 American Academy of Neurology.
FAU - Shelly, Shahar
AU  - Shelly S
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Paul, Pritikanta
AU  - Paul P
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Bi, Hongyan
AU  - Bi H
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Dubey, Divyanshu
AU  - Dubey D
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Milone, Margherita
AU  - Milone M
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Sorenson, Eric J
AU  - Sorenson EJ
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Crum, Brian A
AU  - Crum BA
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Laughlin, Ruple S
AU  - Laughlin RS
AUID- ORCID: 0000-0002-1884-5824
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Liewluck, Teerin
AU  - Liewluck T
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Mandrekar, Jay
AU  - Mandrekar J
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Pittock, Sean J
AU  - Pittock SJ
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Zekeridou, Anastasia
AU  - Zekeridou A
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - McKeon, Andrew
AU  - McKeon A
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Harper, Michael C
AU  - Harper MC
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Mills, John R
AU  - Mills JR
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN.
FAU - Klein, Christopher J
AU  - Klein CJ
AUID- ORCID: 0000-0002-4012-8856
AD  - From the Departments of Neurology (S.S., P.P., H.B., D.D., M.M., E.J.S., B.A.C., 
      R.S.L., T.L., S.J.P., A.Z., A.M., M.C.H., C.J.K.), Laboratory Medicine and 
      Pathology (D.D., S.J.P., A.Z., A.M., J.R.M., C.J.K.), and Biomedical Statistics 
      and Bioinformatics (J.M.), Mayo Clinic Foundation, Rochester, MN. 
      klein.christopher@mayo.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200916
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Autoantibodies)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Algorithms
MH  - Autoantibodies/*blood
MH  - Electrodiagnosis
MH  - Female
MH  - Humans
MH  - Immunologic Tests/*standards
MH  - Male
MH  - Middle Aged
MH  - Myasthenia Gravis/blood/*diagnosis/immunology
MH  - Retrospective Studies
MH  - Sensitivity and Specificity
MH  - Thymoma/blood/*diagnosis/immunology
MH  - Thymus Neoplasms/blood/*diagnosis/immunology
MH  - Young Adult
EDAT- 2020/09/18 06:00
MHDA- 2020/12/17 06:00
CRDT- 2020/09/17 05:38
PHST- 2020/04/04 00:00 [received]
PHST- 2020/07/22 00:00 [accepted]
PHST- 2020/09/18 06:00 [pubmed]
PHST- 2020/12/17 06:00 [medline]
PHST- 2020/09/17 05:38 [entrez]
AID - WNL.0000000000010910 [pii]
AID - 10.1212/WNL.0000000000010910 [doi]
PST - ppublish
SO  - Neurology. 2020 Dec 1;95(22):e3002-e3011. doi: 10.1212/WNL.0000000000010910. Epub 
      2020 Sep 16.