Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure

Jeremy K. Cutsforth-Gregory, Andrew B McKeon, Elizabeth Coon, David M. Sletten, Mariana Suarez, Paola Sandroni, Wolfgang Singer, Eduardo E. Benarroch, Robert D. Fealey, Phillip Anson Low

Research output: Contribution to journalArticle

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Abstract

Objective: To assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and Methods: We searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. Results: Of 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). Conclusion: Ganglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.

Original languageEnglish (US)
Pages (from-to)1440-1447
Number of pages8
JournalMayo Clinic Proceedings
Volume93
Issue number10
DOIs
StatePublished - Oct 1 2018

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Antibodies
Cholinergic Receptors
Hypohidrosis
Sensitivity and Specificity
Orthostatic Hypotension
Nicotinic Receptors
Autoimmunity
ROC Curve
Adrenergic Agents
Autoantibodies
Reflex
Databases

ASJC Scopus subject areas

  • Medicine(all)

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Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure. / Cutsforth-Gregory, Jeremy K.; McKeon, Andrew B; Coon, Elizabeth; Sletten, David M.; Suarez, Mariana; Sandroni, Paola; Singer, Wolfgang; Benarroch, Eduardo E.; Fealey, Robert D.; Low, Phillip Anson.

In: Mayo Clinic Proceedings, Vol. 93, No. 10, 01.10.2018, p. 1440-1447.

Research output: Contribution to journalArticle

Cutsforth-Gregory, JK, McKeon, AB, Coon, E, Sletten, DM, Suarez, M, Sandroni, P, Singer, W, Benarroch, EE, Fealey, RD & Low, PA 2018, 'Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure', Mayo Clinic Proceedings, vol. 93, no. 10, pp. 1440-1447. https://doi.org/10.1016/j.mayocp.2018.05.033
Cutsforth-Gregory, Jeremy K. ; McKeon, Andrew B ; Coon, Elizabeth ; Sletten, David M. ; Suarez, Mariana ; Sandroni, Paola ; Singer, Wolfgang ; Benarroch, Eduardo E. ; Fealey, Robert D. ; Low, Phillip Anson. / Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure. In: Mayo Clinic Proceedings. 2018 ; Vol. 93, No. 10. pp. 1440-1447.
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title = "Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure",
abstract = "Objective: To assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and Methods: We searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. Results: Of 289 patients who met inclusion criteria, 163 (56.4{\%}) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92{\%} specificity and 56{\%} sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25{\%}), a level of at least 0.20 nmol/L had 80{\%} specificity and 59{\%} sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1{\%}). Conclusion: Ganglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25{\%} or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.",
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T1 - Ganglionic Antibody Level as a Predictor of Severity of Autonomic Failure

AU - Cutsforth-Gregory, Jeremy K.

AU - McKeon, Andrew B

AU - Coon, Elizabeth

AU - Sletten, David M.

AU - Suarez, Mariana

AU - Sandroni, Paola

AU - Singer, Wolfgang

AU - Benarroch, Eduardo E.

AU - Fealey, Robert D.

AU - Low, Phillip Anson

PY - 2018/10/1

Y1 - 2018/10/1

N2 - Objective: To assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and Methods: We searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. Results: Of 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). Conclusion: Ganglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.

AB - Objective: To assess antibody level as a test of autonomic failure (AF) associated with ganglionic nicotinic acetylcholine receptor antibody (AChR-Ab) autoimmunity. Patients and Methods: We searched the Mayo Clinic laboratory database of 926 ganglionic AChR-Ab–seropositive patients seen at our institution between October 1, 1997, and April 1, 2015, for initial level of 0.05 nmol/L or higher and contemporaneous autonomic reflex screen (standardized evaluation of adrenergic, cardiovagal, and sudomotor functions) from which Composite Autonomic Scoring Scale (CASS) scores could be calculated. Results: Of 289 patients who met inclusion criteria, 163 (56.4%) were women, median age was 54 years (range, 10-87 years), median antibody level was 0.11 nmol/L (range, 0.05-22.10 nmol/L), and median CASS total score was 2.0 (range, 0-10). Using receiver operating characteristic curve analysis, a level above 0.40 nmol/L predicted severe AF (CASS score, ≥7) with 92% specificity and 56% sensitivity. For at least moderate AF (CASS score ≥4 and anhidrosis ≥25%), a level of at least 0.20 nmol/L had 80% specificity and 59% sensitivity. Levels below 0.20 nmol/L were not predictive of the presence or absence of AF. For predicting orthostatic hypotension, ganglionic AChR-Ab level had excellent specificity above 0.4 nmol/L but lacked sensitivity. Autoantibodies to additional targets were present in 61 patients (21.1%). Conclusion: Ganglionic AChR-Ab level of at least 0.40 nmol/L is a moderately sensitive and highly specific marker for severe AF, as is a level of at least 0.20 nmol/L for moderate AF if CASS score is coupled with anhidrosis of 25% or more, among patients with suspected ganglionic AChR-Ab autoimmune autonomic ganglionopathy. Antibody levels of less than 0.20 nmol/L have little clinical importance in the absence of clinical AF.

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