The Cunningham Panel

Rachel Roth
13 minutes ago
4 min read

Summary:

The Cunningham panel is not evidence-based and is not recommended for diagnosing PANDAS, PANS, or autoimmune encephalitis. PANS and PANDAS remain diagnoses based on clinical criteria. I am happy to review and discuss your results with you to the best of my abilities. I do not routinely recommend the Cunningham panel for the reasons outlined below.

What the Cunningham Panel Is

The Cunningham Panel is a commercial laboratory test developed by Moleculera Labs that measures IgG antibodies against five neuronal targets and assesses their functional effects on neuronal cells. Specifically, it measures:

Anti-dopamine D1 receptor antibodies
Anti-dopamine D2 receptor antibodies
Anti-lysoganglioside-GM1 antibodies
Anti-tubulin antibodies
Calcium/calmodulin-dependent protein kinase II (CaMKII) activation in human neuronal cells [1-2]

What It's Supposed to Do

The panel is marketed as a diagnostic aid for PANDAS and PANS based on the autoimmune hypothesis that streptococcal or other infections trigger antibodies that cross-react with basal ganglia antigens through molecular mimicry. The test purports to detect these pathogenic anti-neuronal antibodies and demonstrate their functional activity (via CaMKII activation), thereby confirming an autoimmune etiology and supporting the diagnosis. [1-2]

Why It Doesn't Work

The evidence shows the Cunningham panel fails as a diagnostic test for several critical reasons:

Poor Diagnostic Accuracy

The most rigorous independent evaluation, published in 2017 by Hesselmark and Bejerot, examined 53 Swedish patients with suspected PANS/PANDAS using comprehensive psychiatric assessment as the reference standard. The study found:

Sensitivities of individual biomarkers: 15-60%
Specificities: 28-92% (meaning up to 72% false positive rate for some markers)
Positive predictive values: only 17-40%
Negative predictive values: 44-74%
Most critically: a majority of healthy controls had pathological Cunningham Panel results
Test-retest reliability was insufficient [3]

This translates to the extremely low specificities cited by the AAP: only 6% for PANS and 10% for PANDAS, meaning 90-94% of positive results would be false positives. [4]

Methodological Flaws in Supporting Evidence

The only published study claiming the panel's utility (Shimasaki 2020) has severe limitations:

Retrospective design examining only patients already diagnosed with PANDAS/PANS
No control group of healthy children or children with other neuropsychiatric conditions
Conducted by Moleculera Labs, the company that manufactures and sells the test
Did not assess diagnostic accuracy for distinguishing PANDAS/PANS from other conditions
Only examined whether antibody changes correlated with symptom changes in patients already diagnosed [1]

The Broader Scientific Context

While there is emerging evidence that anti-neuronal antibodies may play a role in PANDAS/PANS pathophysiology—particularly recent work showing antibodies binding to striatal cholinergic interneurons—this does not validate the Cunningham Panel as a diagnostic test. [4-6] Research-grade antibody studies differ fundamentally from commercial diagnostic tests: they require validation showing the test can accurately distinguish affected patients from healthy controls and from patients with other conditions.

Clinical Bottom Line

The Cunningham Panel measures antibodies that may be biologically interesting in research contexts, but the test lacks the sensitivity, specificity, and reliability required for clinical diagnosis. The high false-positive rate in healthy children means positive results do not confirm PANS/PANS, and the modest sensitivity means negative results do not exclude it—rendering the test clinically useless for individual patient decision-making. [3-4]

What I Tell Patients:

PANS and PANDAS remain diagnoses based on clinical criteria. Clinicians should diagnose through careful history, physical examination, and appropriate workup to exclude other conditions—not through the Cunningham panel. The cost of a Cunningham panel is about $1000, paid privately. The risk of testing (a blood draw) is low, but the results are often confusing and do not impact treatment. Therefore, while I am happy to review and discuss results with you, I do not routinely recommend the Cunningham panel.

The Cunningham panel is not recommended because it has very low specificity (6% for PANS and 10% for PANDAS) and very high positive rates among healthy children.
The results will neither confirm nor eliminate PANS and will not alter planned treatment.
A 2026 narrative review confirms that no currently available biomarker (ie no lab testing)—including the Cunningham Panel—has demonstrated adequate individual-level diagnostic accuracy for PANDAS.
The only published study evaluating the Cunningham panel was conducted by the laboratory that manufactures the test (Moleculera Labs).
The study was small and had significant methodological limitations: it was retrospective, included only patients already diagnosed with PANDAS/PANS, lacked a control group.