Cunningham Panel Reviews – Study incorrectly reviews Cunningham Panel reliability

Authors publish corrigendum to study reviewing Cunningham Panel

A study by Hesselmark and Bejerot¹, which reviews the efficacy and utility of the Cunningham Panel, has several limitations, as acknowledged by the authors in a corrigendum published in the Journal of Neuroimmunology. The study calls into question the test’s reliability but employs invalid collection methods and lacks appropriate healthy controls.

In their correction, entitled “Corrigendum to Biomarkers for diagnosis of pediatric acute neuropsychiatric syndrome (PANS) – sensitivity and specificity of the Cunningham Panel,”² the authors describe utilizing invalid serum collection tubes.

During the Cunningham Panel Review, Invalid Collection Tubes Impact Results

Although the study reviews the use of the Cunningham Panel and its reliability, the collection method was invalid. “We have been informed that Moleculera Labs recommend Red Top glass tubes when collecting blood for the Cunningham Panel,” the authors state.

“In our study, we have used serum sampling tubes (BD Vacutainer® SST™ II Advance tubes, Gold Top) but erroneously reported sampling in “serum sampling tube (BD Vacutainer, yellow top).”

“The use of another blood collection tube than the one recommended by Moleculera could be viewed as a limitation in our study,” the authors point out.

In fact, the autoantibodies tested with the Cunningham Panel™ “have to our knowledge not been tested using the two different types of tubes.”

Using the wrong collection tubes can greatly impact the reliability of test results. “Invalid blood collection methods alone would render the results questionable at best,” explains Richard Frye, M.D. in his correspondence to Translational Psychiatry.³

“But, potential assay interfering substances which could alter the results would render the study void.”

During the Cunningham Panel Review, Insufficient Inclusion and Exclusion Criteria for Healthy Controls Alters Results

“The clinical value of a medical test is highly dependent on applying it to an appropriate symptomatic disease population,” explains Frye.

This study lacked a reliable ‘healthy control’ population. And while it is not mentioned in the Corrigendum, this is a significant flaw.

“Many of their [Hesselmark et al.] healthy controls demonstrated an elevation in the antibody-mediated cell signaling calcium calmodulin-dependent protein kinase II (CaMKII) activation assay,” states Frye.

These elevated levels are likely due to several factors: inclusion of both adults and children; invalid collection methods; and insufficient exclusion and inclusion criteria.

For instance, “when selecting healthy controls, the authors did not exclude family members with a history of psychiatric, autoimmune or movement disorders,” explains Frye.

In fact, patients who were treated for a psychiatric disorder for longer than one year prior to enrolling in the study were included as ‘healthy controls.’ (This is based on the authors’ stated exclusion criteria.)

Furthermore, the study did not screen for, or exclude, ‘healthy controls’ with recent or active infections.