For Wieslab and all International Ordering Physicians and Patients

 

(Please scroll down for International Ordering Instructions)

In a recently published article in the Journal of Neuroimmunology, Hesselmark and Bejerot enrolled 53 patients using the Cunningham Panel, in which they concluded “Clinical use of the Cunningham Panel in diagnosing PANS or PANDAS is not supported by this study.”

After reading their study methods, we learned that they collected patients’ blood specimens in invalid collection tubes (Gold top) , which contain both a clot activator and a serum gel separator. Blood samples drawn in tubes other than the required Glass Red Top 1 tubes (which have no clot activators, no anticoagulants, no preservatives and no serum separator gel) are rejected for testing by Moleculera Labs.

We do not accept serum collected from blood drawn in containers other than Glass Red Top, 2 as data shows interference in the Cunningham Panel assay results. We brought these concerns to the author’s attention, which resulted in the publication of a Corrigendum 3 in the Journal of Neuroimmunology. Unfortunately, the corrigendum referred to a recommendation rather than what is a requirement for the use of glass red top tubes (as specified above).

The Cunningham Panel is clinically validated only for the use of specimens drawn in glass red top tubes. These collection tubes are included in each test kit sent within the U.S., and collection instructions are clearly stated in requisitions for international orders. Our research has shown that blood drawn in tubes other than glass red top tubes yield sporadically unpredictable, and sometimes irreproducible, results with some patient samples. It is unclear at this time what the mechanism of interference is and/or binding properties of the clot activator and serum separator gel in the Gold Top tubes. Since the five-assay Cunningham Panel includes antigen-binding and antibody cell stimulation, there may be more than one mechanism of interference, as results can be increased or decreased in collection tubes with additives. Since the Cunningham Panel has been validated only with glass collection tubes with no additives, as an accredited clinical laboratory we can only accept specimens that are collected in validated collection containers.

We have since learned that all of the Hesselmark et al. specimens in their study were drawn in gold top tubes. Had Moleculera been aware of this, all those specimens would have been rejected. Not all laboratories are able to validate assays in multiple collection tubes, so it is uncertain why the study was performed using an invalid collection tube. We have since offered to work together with the researchers to conduct an additional study utilizing the validated collection tube. We have additional concerns with the Hesselmark and Bejerot study as there was no laboratory evidence that all patients in their control group were infection-free. Since PANDAS/PANS is believed to be a result of an infection-triggered autoimmune response, patients with these disorders may have multiple, and often sub-clinical infections revealed upon appropriate laboratory testing. There is no indication that such testing was performed in the control group. This could be an additional source of test result confusion.


1 Specimen Requirements/Containers, Department of Pathology & Laboratory Medicine, University of California, Irvine, School of Medicine. http://www.pathology.uci.edu/services/specimen-containers.asp Last accessed 12/22/17.

2 Ordering the Cunningham Panel Lab Tests https://www.moleculeralabs.com/order-cunningham-panel-tests/ Last accessed 12/22/17

3 Corrigendum to “Biomarkers for diagnosis of pediatric acute neuropsychiatric syndrome (PANS) – Sensitivity and specificity of the Cunningham Panel” [J. Neuroimmunol. 312. (2017) 31-37] http://www.jni-journal.com/article/S0165-5728(17)30487-3/fulltext Last accessed 12/22/17


The research of Dr. Madeleine Cunningham and the research conducted in conjunction with other institutions [1-16] has clearly demonstrated that the Cunningham Panel biomarker targets are associated with autoimmune neuropsychiatric disorders such as PANDAS/PANS and other neuropsychiatric conditions. We welcome the opportunity to collaborate in well-designed and well-controlled studies to better characterize the clinical utility of these biomarkers in autoimmune neuropsychiatric disorders.

Should you have further questions or wish to order the Cunningham Panel, please connect with:

AONM (our International provider in the U.K.)
Phone number: 0044 3331 210 305
Website: www.aonm.org
Email: info@aonm.org

You may also contact us at Moleculera Labs by email at customerservice@moleculera.com or by calling (405) 239-5250. We will be happy to answer your questions and address any concerns that you may have.


REFERENCES

1 Kirvan, C.A., Swedo, S.E., Heuser, J.S., Cunningham, M.W., Mimicry and autoantibody-mediated neuronal cell signaling in Sydenham chorea. Nature Medicine, 2003. 9(7): p. 914-920.

2 Kirvan, C.A., et al., Antibody-mediated neuronal cell signaling in behavior and movement disorders. J Neuroimmunol, 2006. 179(1-2): p. 173-9.

3 Kirvan, C.A., Swedo, S.E., Kurahara, D., Cunningham, M.W., Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham’s chorea. Autoimmunity, 2006. 39(1): p. 21-9.

4 Kirvan, C.A., Cox, C.J., Swedo, S.E., Cunningham, M.W., Tubulin Is a Neuronal Target of Autoantibodies in Sydenham’s Chorea. Journal of Immunology, 2007. 178: p. 7412-7421.

5 Ellis, N.M., et al., Priming the immune system for heart disease: a perspective on group A streptococci. J Infect Dis, 2010. 202(7): p. 1059-67.

6 Brimberg, L., et al., Behavioral, pharmacological, and immunological abnormalities after streptococcal exposure: a novel rat model of Sydenham chorea and related neuropsychiatric disorders. Neuropsychopharmacology, 2012. 37(9): p. 2076-87.

7 Cunningham, M.W., Autoimmunity: an infection-related risk? Curr Opin Rheumatol, 2013. 25(4): p. 477-9.

8 Ben-Pazi, H., J.A. Stoner, and M.W. Cunningham, Dopamine receptor autoantibodies correlate with symptoms in Sydenham’s chorea. PLoS One, 2013. 8(9): p. e73516.

9 Cox, C.J., et al., Brain Human Monoclonal Autoantibody from Sydenham Chorea Targets Dopaminergic Neurons in Transgenic Mice and Signals Dopamine D2 Receptor: Implications in Human Disease. The Journal of Immunology, 2013. 191(11): p. 5524-5541.

10 Lotan, D., et al., Behavioral and neural effects of intra-striatal infusion of anti-streptococcal antibodies in rats. Brain Behav Immun, 2014. 38: p. 249-62.

11 Singer, H.S., et al., Neuronal antibody biomarkers for Sydenham’s chorea identify a new group of children with chronic recurrent episodic acute exacerbations of tic and obsessive compulsive symptoms following a streptococcal infection. PLoS One, 2015. 10(3): p. e0120499.

12 Chang, K., et al., Clinical evaluation of youth with pediatric acute-onset neuropsychiatric syndrome (PANS): recommendations from the 2013 PANS Consensus Conference. J Child Adolesc Psychopharmacol, 2015. 25(1): p. 3-13.

13 Cox, C.J., Zuccolo, A. J., Edwards, E. V., Mascaro-Blanco, A., Alvarez, K., Stoner, J., Chang, K., Cunningham, M. W., Antineuronal antibodies in a heterogeneous group of youth and young adults with tics and obsessive-compulsive disorder. J Child Adolesc Psychopharmacol, 2015. 25(1): p. 76-85.

14 Graziella Orefici, P., Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS), in Streptococcus pyogenes: Basic Biology to Clinical Manifestations. 2016.

15 Cunningham, M.W. and C.J. Cox, Autoimmunity against dopamine receptors in neuropsychiatric and movement disorders: a review of Sydenham chorea and beyond. Acta Physiol (Oxf), 2016. 216(1): p. 90-100.

16 Frankovich, J., et al., Clinical Management of Pediatric Acute-Onset Neuropsychiatric Syndrome: Part II—Use of Immunomodulatory Therapies. Journal of Child and Adolescent Psychopharmacology, 2017.