NMO (aquaporin 4) antibodies
Neuromyelitis optica (NMO) associated antigen, a water channel protein, known as aquaporin 4 (AQP4) is found both in the central and peripheral tissues. Detection of AQP4 antibody is clinically useful in differentiating between NMO and other optic neuritis or myelitis. Unlike multiple sclerosis, a patient with AQP4 antibody can benefit from plasmapheresis and immunosuppression.
On cerebellum, AQP4 is found in the juxtaposed pial membrane, microvessels in the white matter, molecular layer and granular layer.
Often, AQP4 antibody is also associated with the staining of the cytoplasm of the granular cells: Such reactivity is also found in the CSF.
AQP4 transfected HEK cell system is a newer test with higher sensitivity and has superseded detection by cerebellum.
Clinical: Neuromyelitis optica (also known as Devic's disease, ~65%) is an immune-mediated demyelinated disorder of the optic nerve and spinal cord. The disorder resembles multiple sclerosis (MS) and the two cannot be distinguished from one another.
Treatment is different for each disorder therefore important to distinguish it from MS.
Anti-glial nuclear antibody (AGNA) antibodies
Recent emergence of another antibody directed against the Bergmann glia of the Purkinje cell layer of cerebellum has been described in patients with PNS (usually Lambert Eaton myasthenic syndrome) associated with SCLC. The target for this antibody is SOX1 protein. Both SOX1 and SOX2 are targets for the AGNA, with higher positivity seen against SOX1.
• 79yr old lady, admitted with right sided chest pain
• Weight loss over the past few months.
• Swallowing difficulties
• A chest X-ray on admission revealed a right sided lesion
• CT thorax/abdomen revealed a large mass in the posterior mediastinum
• Extensive metastases noted within the chest and abdomen
Patients serum generated the above staining on rat cerebellum which was confirmed to be SOX1 antibody. Immunofluorescence shows characteristic staining of the nuclei of Bergmann glia.
Confirmation of SOX-1 antibody can be done on a line blot apinted with a recombinant antigen.
Glutamic acid decarboxylase (GAD) antibodies
GAD antibody on primate pancreas (Islet cell antibody has similar distribution). The target antigens are GAD 67 and GAD 65 which are associated with Stiff-man syndrome and insulin dependent diabetes mellitus respectively.
Low magnification: GAD staining the granular layer in the primate cerebellum. In contrast to amphiphysin there is a lack of staining in the molecular layer.
Neurological syndrome: Stiff person’s syndrome or diffuse hypertonia. GAD has also been reported in cerebellar ataxia, epilepsy and myoclonus.
Tumour associated: Breast, colon, small cell lung carcinoma
Myelin associated glycoprotein (MAG) antibodies
Primate sciatic nerve showing anti-MAG IgM staining the inner and outer myelin of axons (target is a 100 kDa glycoprotein).
Neurological syndrome: Peripheral neuropathy
Associated tumour: Waldenstrom's macroglobulinaemia, multiple myeloma
Skeletal muscle antibodies
Human IgG antibody to primate skeletal muscle showing staining of the striation. This pattern is similar to cardiac antifibrillary antibody.
Antigen: contractile elements of striated muscle
Disease: myasthenia gravis