Autoimmune Encephalitis

Encephalitis is a broad clinical term encompassing cases of inflammation of the brain’s parenchymal tissues.  Several distinct conditions can lead to similar symptomology, including viral infection, side effects of medications, and autoimmune attack.  Autoimmune encephalitis refers to the cases wherein the body erroneously targets cells in the central nervous system as pathogens, resulting in the immune system attacking them directly.

Multiple different antibodies can be responsible for autoimmune encephalitis, resulting in significant difficulties in accurate diagnosis.

Glutamate Receptor (NMDA) Antibodies

Anti-NMDAR encephalitis is the most common presentation of the disorder.  Symptoms include fever, headache, and exhaustion, which can progress over time into psychosis.  Eventually, seizures, respiratory distress, and blood pressure and heart rate abnormalities can develop.

Antibodies (Ab) can come to target the cells of the central nervous system (CNS) as a result of teratomas – N-methyl D-aspartate receptors (NMDAR) on tumors are targeted and attacked via glutamate (Glu) channels, which can lead to decreased immunological tolerance for the Abs.  This result in autoantibodies crossing the blood brain barrier and blocking or destroying Glu channels on NMDARs in the CNS.

Transfected human cells and neurological tissue sections taken from rat brains are fixed and exposed to sera and/or cerebrospinal fluid (CSF) from patients and assessed for binding.  If positive, NMDAR antibodies attach themselves to the substrate.  Subsequently, the attached antibodies are stained with dye and made visible via fluorescence microscopy for assessment and quantification.

Anti-GABA B (B1/B2) Antibodies

Symptoms include strange behavioral patterns, psychosis, sleep disorders, and most commonly, seizures (~90% of patients).  Left untreated, can result in coma and death.

Approximately 50% of patients have an underlying small cell lung carcinoma.  Antibodies come to target the cells of the central nervous system (CNS) through the gamma aminobutyric acid B (GABAB) receptors, resulting in either their inhibition or destruction.  Early diagnosis can yield positive patient response rates as a result of immunotherapy and tumor treatment.

Sera and cerebrospinal fluid (CSF) from affected patients are tested against transfected human cells and tissues from rat brains and assessed for binding.  Subsequently, any attached antibodies are dyed, assessed and quantified via fluorescence microscopy.

Anti-DPPX Antibodies

Dipeptidyl aminopeptidase-like protein 6 (DPPX) is a protein that interacts with the voltage-gated potassium channel Kv4, typically regulating membrane excitability in the CA1 cells of the hippocampus.  Autoimmune DPPX Ab targeting can therefore produce membrane hyperexcitability in patients, yielding muscle spasms, tremors, and seizures.  Common initial symptoms include sudden weight loss, diarrhea, and other gastrointestinal symptoms.  Other symptoms can include restlessness, memory loss, confusion, and hallucinations.  In some patients, DPPX antibody (Ab) encephalitis can be associated with cancer of the lymphatic system, and therefore serological analysis producing positive results should not exclude tumor investigation.  The disorder is responsive to immunotherapy, and therefore early diagnosis is crucial.

Sera and cerebrospinal fluid (CSF) from suspected patients are tested against transfected human cells and tissues from rat brains and assessed for binding.  Subsequently, any attached antibodies are dyed, assessed and quantified via fluorescence microscopy.

Anti-VGKC (LGI1 and CASPR2) Antibodies

Anti-VGKC encephalitis is caused by antibodies that target the voltage-gated potassium channel complex (VGKC-complex).

Many variants of autoimmune encephalitis feature antibodies that target intracellular antigens, usually as a result of the immune system targeting cancer cells (paraneoplastic syndromes).  Anti-VGKC encephalitis, conversely, typically targets synaptic proteins and is generally unassociated with underlying tumors (nonparaneoplastic).

Antibodies associated with anti-VGKC encephalitis do not generally target the VGKC channel itself.  Instead, they are directed towards associated or complexed proteins.  Common targets include the Leucine-rich, glioma inactivated 1 (LGI1) protein (~60% of patients), the contactin-associated protein 2 (CASPR2, ~20% of patients), contactin-2 itself (transiently expressed axonal surface glycoprotein-1, or TAG-1, in ~5% of cases), or otherwise feature antibodies of unknown specificity (~20% of patients).  Symptoms depend on the targeted antigen, but features often overlap.

The most characteristic feature of anti-LGI1 Ab positive patients are cognitive impairment, in the form of amnesia or confusion, and seizures.  Immunotherapy and, in the <10% of patients that do feature underlying cancers, tumor removal typically yield substantial regression of symptoms and good prognosis.

Anti-CASPR2 Abs can result in muscle spasms, amnesia, anxiety, depression, and seizures.  In patients without tumors, immunotherapy generally results in improved symptoms.  In paraneoplastic cases, prognosis is generally poorer.

Sera and cerebrospinal fluid (CSF) from suspected patients are tested against transfected human cells and tissues from rat brains and assessed for binding.  Subsequently, any attached antibodies are dyed, assessed and quantified via fluorescence microscopy.

MOSAIC-6 Antibody Testing

Includes cell-based assays for all of the antibodies outlined previously, permitting a broad analysis of the spectrum of potential antibodies resulting in autoimmune encephalitis.

Laboratory Requisition

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