Add-On: Leaky Brain - Array 20
The Add-On: Leaky Brain – Array 20 measures serum IgG and IgA antibodies to blood-brain barrier proteins (occludin, claudins, aquaporin-4, S100B, GFAP, myelin basic protein) and neuronal antigens. It is an exploratory functional-medicine panel used to assess immune reactivity in unexplained cognitive, mood, or neuropsychiatric symptoms, not a diagnostic test for specific neurological disease.
7
Biomarkers
Blood (serum)
Sample
14–21 business days
Turnaround
No
Fasting
What is the Array 20 test?
The Add-On: Leaky Brain – Array 20 is a specialised antibody panel measuring serum IgG and IgA reactivity to blood-brain barrier proteins, astrocytic markers, and neuronal antigens. It is positioned within functional and integrative medicine as an exploratory tool to assess whether immune reactivity to central nervous system barrier components correlates with unexplained cognitive decline, mood disorders, or chronic neurological symptoms in patients whose conventional diagnostic work-up has not yielded a structural or definitive autoimmune diagnosis. The panel does not diagnose a specific neurological disease. Rather, it is ordered alongside comprehensive autoimmune, metabolic, and neuroinflammatory assessments to identify patterns of immune activation that may inform personalised treatment strategies aimed at reducing systemic inflammation, supporting gut-barrier integrity, and addressing potential blood-brain barrier permeability. Practitioners use Array 20 as one component of a broader investigative approach in patients who do not fit established diagnostic criteria yet exhibit persistent neuropsychiatric symptoms.
What does the Array 20 test measure?
The blood-brain barrier is a specialised endothelial interface between the systemic circulation and the central nervous system parenchyma, formed by tight junctions between capillary endothelial cells and supported by astrocyte endfeet, pericytes, and a basement membrane. It selectively restricts the passage of macromolecules and immune cells into brain tissue. In some neuroinflammatory and systemic autoimmune conditions, barrier integrity may be compromised, and immune reactivity to barrier proteins has been hypothesised as a marker of that compromise.
Cyrex Array 20 measures serum IgG and IgA antibodies to a panel of proteins associated with the blood-brain barrier, including tight-junction components (occludin, claudins, zonulin), astrocyte markers (S100B, aquaporin-4), and neuronal antigens. Elevated antibody titres are interpreted within a functional or integrative framework as potential evidence of barrier permeability or neuroinflammatory processes, though none of the Array 20 antibodies is a validated diagnostic marker for a specific neurological disease.
S100B is a calcium-binding protein expressed predominantly in astrocytes and is released into blood following astrocytic activation or injury. Cerebrospinal fluid and serum S100B concentrations are studied as biomarkers of central nervous system trauma or pathology, but antibodies to S100B reflect an immune response to the protein rather than direct measurement of the protein itself.
Antibodies to S100B are hypothesised to reflect ongoing astrocyte damage or immune cross-reactivity in the setting of neuroinflammation. Their clinical utility remains exploratory; they are not part of routine neurological diagnostics but may be included in functional-medicine evaluations of unexplained cognitive or neuropsychiatric symptoms.
Occludin and claudins are transmembrane proteins integral to tight junctions in vascular endothelia, including those of the blood-brain barrier. Tight junctions regulate paracellular permeability; their disruption has been implicated in barrier breakdown in models of neuroinflammation, stroke, and infection.
Antibodies to tight-junction proteins are measured as exploratory markers of blood-brain barrier compromise. The assay is not standardised across laboratories, and reactivity does not yet map to a specific disease diagnosis but may inform integrative treatment strategies aimed at reducing systemic inflammation.
Aquaporin-4 is a water-channel protein concentrated in astrocyte endfeet at the blood-brain interface and along the glial limitans. In neuromyelitis optica spectrum disorder, high-affinity IgG against AQP4 causes complement-mediated astrocyte injury and demyelination; diagnosis requires a validated cell-based assay.
Array 20 includes an antibody screen for aquaporin-4 as one component of a broader barrier-permeability panel. The assay is exploratory and not a substitute for the diagnostic NMOSD test. Positive results require neurology referral and confirmatory testing if central demyelination is suspected.
Glial fibrillary acidic protein is an intermediate filament found in astrocytes; serum GFAP has been studied as a biomarker of astrocytic injury in trauma, stroke, and neurodegenerative disease. Antibodies to GFAP, distinct from measurement of the protein itself, are occasionally seen in autoimmune encephalitides and as an exploratory marker in functional panels.
GFAP antibodies may reflect astrocytic damage or autoimmune reactivity but are not yet validated for routine clinical use. They are measured in exploratory contexts or as part of broader autoimmune encephalitis work-ups.
Myelin basic protein is a major structural component of central nervous system myelin sheaths. Antibodies to MBP have been studied in multiple sclerosis and other demyelinating conditions, though they lack diagnostic specificity.
MBP antibodies are an exploratory marker in suspected neuroinflammation or demyelination. They do not diagnose or exclude multiple sclerosis, which remains a clinical and MRI diagnosis supplemented by cerebrospinal fluid oligoclonal bands.
IgA responses reflect mucosal immune activation and have been proposed as markers of gut-brain axis dysfunction or systemic translocation of antigens. The relationship between serum IgA to neuronal antigens and central nervous system pathology is hypothetical and under investigation.
Neuronal IgA antibodies are measured in a functional-medicine framework as exploratory markers of cross-reactivity or systemic inflammation. They are not diagnostic of a neurological disease and should be interpreted in the broader clinical and laboratory context.
Why is the Array 20 test ordered?
- Unexplained or treatment-resistant cognitive impairment, brain fog, or memory decline in the absence of structural imaging abnormalities or established neurodegenerative biomarkers
- Chronic mood disorders, anxiety, or depression that have not responded adequately to standard pharmacotherapy and in which neuroinflammation is hypothesised
- Suspected autoimmune encephalitis or central nervous system autoimmunity after initial conventional serologies (ANA, paraneoplastic panels) are unrevealing but clinical suspicion persists
- Patients with systemic autoimmune disease (rheumatoid arthritis, lupus, coeliac disease) who develop new cognitive or neuropsychiatric symptoms and for whom a link between systemic and central nervous system inflammation is being explored
- Functional-medicine evaluations of suspected gut-brain axis dysfunction, particularly in patients with intestinal hyperpermeability ('leaky gut') and concurrent neurological complaints
- Follow-up after interventions targeting systemic inflammation, intestinal permeability, or dietary triggers to document changes in antibody reactivity over time
- Screening of at-risk individuals, such as those with family history of neuroinflammatory disease, traumatic brain injury, or chronic systemic inflammatory conditions, who wish to explore subclinical immune activation before overt neurological symptoms appear
Sample collection and turnaround
Sample type
Blood (serum)
Fasting required
No
Collection method
Venipuncture at patient service centre
Turnaround
14–21 business days
Collection notes
Phlebotomy required; serum is shipped to Cyrex Laboratories. The patient or practitioner must arrange for venepuncture at a draw site that can process and ship speciality-lab specimens. Cyrex provides collection instructions and shipping materials.
Specimen requirements
Serum separator tube; minimum volume per Cyrex protocol (typically 2–3 mL serum). Specimen must be centrifuged, separated, and frozen if not shipped immediately. Follow Cyrex shipping and handling instructions precisely to avoid specimen rejection.
What can affect Array 20 results?
Patients with rheumatoid arthritis, lupus, Sjögren syndrome, or coeliac disease may exhibit polyclonal antibody elevation and non-specific cross-reactivity, so results should be interpreted in the context of established systemic autoimmunity rather than as independent evidence of primary central nervous system pathology.
Blood-brain barrier disruption and astrocyte injury following trauma or ischaemia can release neuronal and barrier antigens into the circulation, potentially triggering antibody production; timing relative to the injury is relevant to interpretation.
Acute infections can transiently increase blood-brain barrier permeability and stimulate immune reactivity to central nervous system antigens; testing during or shortly after infection may yield non-specific elevation.
Immunosuppressants, corticosteroids, and biologic agents may dampen antibody responses; conversely, checkpoint inhibitors and immune modulators may unmask or elevate autoantibody titres.
Array 20 uses a proprietary multiplexed immunoassay platform; results are not interchangeable with other laboratories' blood-brain barrier antibody panels, and serial testing should be performed at the same laboratory.
Some antibodies (for example, aquaporin-4 or GFAP antibodies) may be elevated in early or subclinical autoimmune encephalitides; positive findings warrant further conventional neurology work-up and should not be dismissed as false positives without clinical correlation.
What do Array 20 results mean?
Elevated
Elevated antibody reactivity to one or more Array 20 antigens is interpreted within a functional framework as potential evidence of blood-brain barrier compromise, astrocytic injury, or immune cross-reactivity to central nervous system proteins. It does not establish a specific neurological diagnosis. Practitioners correlate positive findings with clinical history, neuroimaging, cerebrospinal fluid studies, and other autoimmune markers. For example, elevated aquaporin-4 antibodies require referral to neurology and cell-based confirmatory testing if neuromyelitis optica is suspected; elevated tight-junction antibodies may prompt interventions targeting intestinal permeability and systemic inflammation. The pattern and magnitude of elevation guide whether conventional neurology referral, additional autoimmune testing, or integrative treatment strategies are warranted.
Normal
Results within the laboratory-defined reference range indicate no significant antibody elevation. This is reassuring in the context of a functional-medicine evaluation but does not exclude all forms of neuroinflammation or blood-brain barrier dysfunction, which may not always generate detectable serum antibody responses. Clinical judgement and correlation with symptoms, imaging, and other laboratory findings remain essential.
Reduced
Low or negative antibody titres suggest the absence of significant immune reactivity to blood-brain barrier and neuronal antigens at the time of testing. They do not exclude neurological disease, particularly if symptoms are caused by structural, vascular, infectious, or non-immune mechanisms. Interpretation requires clinical context — a negative Array 20 in a patient with progressive dementia does not obviate the need for conventional dementia work-up.
Note: Array 20 is a functional, exploratory panel, not a validated diagnostic test for any specific neurological disease. Its antibodies are not part of mainstream neurology guidelines, and positive results should not replace conventional diagnostic pathways for multiple sclerosis, neuromyelitis optica, autoimmune encephalitis, or dementia. The panel is best used as an adjunct in patients whose conventional work-up is unrevealing but in whom integrative practitioners suspect immune-mediated barrier dysfunction. Serial testing can document trends but must be performed at the same laboratory using the same platform. Practitioners should ensure patients understand the exploratory nature of the test and that it forms part of a broader investigative and therapeutic strategy rather than a stand-alone diagnostic tool.
Frequently asked questions
Array 20 is a speciality antibody panel measuring IgG and IgA reactivity to blood-brain barrier proteins (tight-junction components, astrocyte markers, aquaporin-4) and neuronal antigens. It is used in functional medicine to explore immune activation in patients with unexplained cognitive, mood, or neuropsychiatric symptoms.
How to access the Array 20 test
The Array 20 reference page is free and open to all practitioners. Create a free practitioner account to see pricing, save tests to your list, and generate requisition forms. Verification takes 1–2 business days.
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Published: October 7, 2026
Last reviewed: October 7, 2026
- Banks WA. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des. (2005)
- Daneman R, Prat A. The blood-brain barrier. Cold Spring Harb Perspect Biol. (2015)
- Graus F, et al. A clinical approach to diagnosis of autoimmune encephalitis. Lancet Neurol. (2016)
- Vojdani A, et al. Novel diagnosis of neural-specific antibodies by ELISA. (Verify citation for Array 20 validation studies.) (2020)
- Lennon VA, et al. IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med. (2005)
This content is for licensed healthcare practitioners only and does not constitute medical advice. Clinical decisions should be based on the full clinical picture and not on any single test result.
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