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J Neuroimmunol. 2020 Feb 15;339:577138. doi: 10.1016/j.jneuroim.2019.577138. Epub 2019 Dec 15.

Evaluation of the Cunningham Panel™ in pediatric autoimmune neuropsychiatric disorder associated with streptococcal infection (PANDAS) and pediatric acute-onset neuropsychiatric syndrome (PANS): Changes in antineuronal antibody titers parallel changes in patient symptoms.

Author information

1
Moleculera Labs, Inc., 755 Research Parkway, Suite 410, Oklahoma City, OK 73104, United States of America. Electronic address: shimasakic@moleculera.com.
2
Barrow Neurological Institute, Phoenix Children's Hospital, 1919 East Thomas Rd, Department of Child Health, University of Arizona College of Medicine-Phoenix, Phoenix, AZ, United States of America.
3
The PANS/PANDAS Institute, 545 Island Road, Suite 1D, Ramsey, NJ 07446, United States of America.
4
Division of Infectious Diseases, University of Missouri School of Medicine, Columbia, MO, United States of America.
5
The Kaplan Center for Integrative Medicine, 6828 Elm Street, Suite 300, McLean, VA 22101, United States of America.
6
IMMUNOe Health and Research Centers, 6801 South Yosemite Street, Centennial, CO 80112, United States of America.
7
Medical Arts Psychotherapy Associates, P.A., 33 Overlook Road, Suite 406, Summit, NJ 07901, United States of America.
8
Private Practice Neurology, 325 Boston Post Rd., Suite 1D, Orange, CT 06477, United States of America.
9
TherapyWorks ATL, 621 North Avenue NE, Atlanta, GA 30308, United States of America.
10
Section of Endocrinology and Diabetes, University of Oklahoma Department of Medicine, 1000 N Lincoln Blvd., Oklahoma City, OK 73104, United States of America.
11
1261 E. Hillsdale Blvd., Foster City, CA 94404, United States of America.
12
Armonk Integrative Medicine, Private Practice, Pediatrics, 99 Business Park Drive, Armonk, NY 10504, United States of America.
13
Latimer Neurology Center, 1101 30th Street NW Suite #320, Washington, DC 20007, United States of America.
14
Moleculera Labs, Inc., 755 Research Parkway, Suite 410, Oklahoma City, OK 73104, United States of America.
15
Moleculera Labs, Inc., 755 Research Parkway, Suite 410, Oklahoma City, OK 73104, United States of America; The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America.
16
The University of Oklahoma Health Sciences Center, Oklahoma City, OK, 73104, United States of America.

Abstract

OBJECTIVE:

This retrospective study examined whether changes in patient pre- and post-treatment symptoms correlated with changes in anti-neuronal autoantibody titers and the neuronal cell stimulation assay in the Cunningham Panel in patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infection (PANDAS), and Pediatric Acute-onset Neuropsychiatric Syndrome (PANS).

METHODS:

In an analysis of all tests consecutively performed in Moleculera Labs' clinical laboratory from April 22, 2013 to December 31, 2016, we identified 206 patients who were prescribed at least one panel prior to and following treatment, and who met the PANDAS/PANS diagnostic criteria. Patient follow-up was performed to collect symptoms and treatment or medical intervention. Of the 206 patients, 58 met the inclusion criteria of providing informed consent/assent and documented pre- and post-treatment symptoms. Clinician and parent-reported symptoms after treatment or medical intervention were categorized as "Improved/Resolved" (n = 34) or "Not-Improved/Worsened" (n = 24). These were analyzed for any association between changes in clinical status and changes in Cunningham panel test results. Clinical assay performance was also evaluated for reproducibility and reliability.

RESULTS:

Comparison of pre- and post-treatment status revealed that the Cunningham Panel results correlated with changes in patient's neuropsychiatric symptoms. Based upon the change in the number of positive tests, the overall accuracy was 86%, the sensitivity and specificity were 88% and 83% respectively, and the Area Under the Curve (AUC) was 93.4%. When evaluated by changes in autoantibody levels, we observed an overall accuracy of 90%, a sensitivity of 88%, a specificity of 92% and an AUC of 95.7%. Assay reproducibility for the calcium/calmodulin-dependent protein kinase II (CaMKII) revealed a correlation coefficient of 0.90 (p < 1.67 × 10-6) and the ELISA assays demonstrated test-retest reproducibility comparable with other ELISA assays.

CONCLUSION:

This study revealed a strong positive association between changes in neuropsychiatric symptoms and changes in the level of anti-neuronal antibodies and antibody-mediated CaMKII human neuronal cell activation. These results suggest there may be clinical utility in monitoring autoantibody levels and stimulatory activity against these five neuronal antigen targets as an aid in the diagnosis and treatment of infection-triggered autoimmune neuropsychiatric disorders. Future prospective studies should examine the feasibility of predicting antimicrobial and immunotherapy responses with the Cunningham Panel.

KEYWORDS:

Antineuronal antibodies; Autoimmune encephalopathy; Basal ganglia encephalitis; Basal ganglia encephalopathy; CaMKII; Cunningham Panel; PANDAS, PANS

PMID:
31884258
DOI:
10.1016/j.jneuroim.2019.577138
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